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1.  Life Course Trajectories of Systolic Blood Pressure Using Longitudinal Data from Eight UK Cohorts 
PLoS Medicine  2011;8(6):e1000440.
Analysis of eight population-based and occupational cohorts from the UK reveals the patterns of change of blood pressure in the population through the life course.
Background
Much of our understanding of the age-related progression of systolic blood pressure (SBP) comes from cross-sectional data, which do not directly capture within-individual change. We estimated life course trajectories of SBP using longitudinal data from seven population-based cohorts and one predominantly white collar occupational cohort, each from the United Kingdom and with data covering different but overlapping age periods.
Methods and Findings
Data are from 30,372 individuals and comprise 102,583 SBP observations spanning from age 7 to 80+y. Multilevel models were fitted to each cohort. Four life course phases were evident in both sexes: a rapid increase in SBP coinciding with peak adolescent growth, a more gentle increase in early adulthood, a midlife acceleration beginning in the fourth decade, and a period of deceleration in late adulthood where increases in SBP slowed and SBP eventually declined. These phases were still present, although at lower levels, after adjusting for increases in body mass index though adulthood. The deceleration and decline in old age was less evident after excluding individuals who had taken antihypertensive medication. Compared to the population-based cohorts, the occupational cohort had a lower mean SBP, a shallower annual increase in midlife, and a later midlife acceleration. The maximum sex difference was found at age 26 (+8.2 mm Hg higher in men, 95% CI: 6.7, 9.8); women then experienced steeper rises and caught up by the seventh decade.
Conclusions
Our investigation shows a general pattern of SBP progression from childhood in the UK, and suggests possible differences in this pattern during adulthood between a general population and an occupational population.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About a third of US and UK adults have high blood pressure (hypertension). Although hypertension has no obvious symptoms, it can lead to life-threatening heart attacks, stroke, and other forms of cardiovascular disease (CVD). It is diagnosed by measuring blood pressure—the force that blood moving around the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic blood pressure [SBP]) and lowest when the heart is re-filling with blood (diastolic blood pressure [DBP]). Normal adult blood pressure is defined as an SBP of less than 130 millimeters of mercury (mm Hg) and a DBP of less than 85 mm Hg (a blood pressure of 130/85). A reading of more than 140/90 indicates hypertension. Many factors affect blood pressure, but overweight people and individuals who eat fatty or salty food are at high risk of developing hypertension. Moreover, blood pressure tends to increase with age. Mild hypertension can often be corrected by making lifestyle changes, but many people take antihypertensive drugs to reduce their blood pressure.
Why Was This Study Done?
Several trials have indicated that SBP is an important, modifiable risk factor for CVD. But, to determine the best way to prevent CVD, it is important to understand how SBP changes through life and how lifestyle factors affect this age-related progression. Textbook descriptions of age-related changes in SBP are based on studies that measured SBP at a single time point in groups (cohorts) of people of different ages. However, such “cross-sectional” studies do not capture within-individual changes in SBP and may be affected by environmental effects related to specific historical periods. The best way to measure age-related changes in SBP is through longitudinal studies in which SBP is repeatedly measured over many years in a single cohort. Such studies are underway, but it will be some decades before individuals in these studies reach old age. In this study, therefore, the researchers use data from multiple UK cohorts that had repeated SBP measurements taken over different but overlapping periods of life to investigate the life course trajectory of SBP.
What Did the Researchers Do and Find?
The researchers used statistical models to analyze data from longitudinal studies of SBP in seven population-based cohorts (the participants were randomly chosen from the general population) and in one occupational cohort (civil servants). SBP measurements were available for 30,372 individuals with ages spanning from seven years to more than 80 years. The researchers' analysis revealed four phases of SBP change in both sexes: a rapid increase in SBP during adolescent growth, a gentler increase in early adulthood, a midlife acceleration beginning in the fourth decade of life, and a period in late adulthood when SBP increases slowed and then reversed. This last phase was less marked when people taking antihypertensive drugs were excluded from the analysis. After adjusting for increases in body mass index (a measure of body fat) during adulthood, the magnitude of the SBP age-related changes was similar but the average SBP at each age was lower. Compared to the population-based cohorts, the occupational cohort had a lower average SBP, a shallower annual increase in SBP, and a later midlife acceleration, possibly because of socially determined modifiable SBP-related factors such as diet and lifestyle. Finally, although women had lower SBPs in early adulthood than men, they experienced steeper midlife SBP rises (probably because of a menopause-related effect on salt sensitivity) so that by the seventh decade of life, men and women had similar average SBPs.
What Do These Findings Mean?
These findings describe the general pattern of age-related progression of SBP from early childhood in the UK. The findings may not be generalizable because other populations may be exposed to different distributions of modifiable factors. In addition, their accuracy may be affected by differences between cohorts in how SBP was measured. Nevertheless, these findings—in particular, the slower midlife increase in SBP in the occupational cohort than in the population-based cohorts—suggest that the key determinants of age-related increases in blood pressure are modifiable and could be targeted for CVD prevention. Further research is now needed to identify exactly which factors affect the life course trajectory of SBP and to discover when these factors have their greatest influence on SBP.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000440.
The US National Heart Lung and Blood Institute has patient information about high blood pressure (in English and Spanish)
The American Heart Association provides information on high blood pressure and on cardiovascular diseases (in several languages)
The UK National Health Service Choices Web site also provides detailed information for patients about hypertension and about cardiovascular disease
MedlinePlus provides links to further information about high blood pressure, heart disease, and stroke (in English and Spanish)
doi:10.1371/journal.pmed.1000440
PMCID: PMC3114857  PMID: 21695075
2.  Hypertension Subtype and Risk of Cardiovascular Disease in Chinese Adults 
Circulation  2008;118(15):1558-1566.
Background
We examined the relationship between hypertension subtype and cardiovascular disease (CVD) incidence and mortality in Chinese adults.
Methods and Results
We conducted a prospective cohort study in a nationally representative sample of 169,871 Chinese men and women aged 40 years and older. Data on systolic (SBP) and diastolic blood pressure (DBP) and other variables were obtained at a baseline examination in 1991 using standard protocols. Follow-up evaluation was conducted in 1999–2000, with a response rate of 93.4%. Hypertension subtypes were defined as combined systolic and diastolic hypertension (SDH: SBP≥140 and DBP≥90 mm Hg), isolated systolic hypertension (ISH: SBP≥140 and DBP<90 mm Hg), isolated diastolic hypertension (IDH: SBP<140 and DBP≥90 mm Hg), and two categories of treated hypertension (SBP<140 and DBP<90 mm Hg or SBP≥140 and/or DBP≥90 mm Hg). After excluding participants with missing BP values, 169,577 adults were included in the analyses. Compared to normotensives, relative risks (95% confidence interval) of CVD incidence and mortality were 2.73 (2.60–2.86) and 2.53 (2.39–2.68) for SDH, 1.78 (1.69–1.87) and 1.68 (1.58–1.78) for ISH, 1.59 (1.43–1.76) and 1.45 (1.27–1.65) for IDH, 2.01 (1.64–2.48) and 1.61 (1.28–2.03) for treated hypertension with SBP<140 and DBP<90 mm Hg, and 3.37 (3.07–3.69) and 2.88 (2.60–3.19) for treated hypertension with SBP≥140 and/or DBP≥90 mm Hg, respectively, after adjustment for important covariables.
Conclusions
Our results indicate that all hypertension subtypes are associated with significantly increased risk of CVD in Chinese adults. Primary prevention of hypertension should be a public health priority in the Chinese population.
doi:10.1161/CIRCULATIONAHA.107.723593
PMCID: PMC2735390  PMID: 18809800
hypertension; cardiovascular disease; relative risk; Chinese
3.  Effect of the DASH Diet on Pre- and Stage 1 Hypertensive Individuals in a Free-Living Environment 
Background:
Dietary Approaches to Stop Hypertension (DASH) has been shown to successfully reduce systolic (SBP) and diastolic blood pressure (DBP) when evaluated in clinically controlled environments but there is a lack of information regarding the efficacy of the original DASH diet when it is applied in a free-living environment.
Purpose:
To provide descriptive data as to the changes in blood pressure individuals could expect to achieve when following the DASH diet in a free-living environment for 4-weeks with no additional behavioral modifications.
Methods:
Twenty, pre- and stage 1 hypertensive participants were randomly split into 2 groups; DASH (males N = 5, females N = 5, age = 38.5 ± 10.8) and control (males N = 7, females N = 3, age = 38.1 ± 11.1). The DASH group was instructed on how to follow the DASH diet on their own for 4-weeks while the control group continued their normal diet. SBP, DBP, body weight, 3-day food diaries and physical activity recall questionnaire data were collected pre and post intervention using a traditional person-to-person instructional technique.
Results:
Two-way ANOVA demonstrated that there was a significant group (DASH, control) by time (pre, post) interaction for SBP (P = 0.003) and no significant effects for DBP. The interaction was due to a significant reduction (P < 0.001) in SBP in the DASH group (pre: 141.3 ± 11.3 mmHg vs. post: 130.7 ± 9.1 mmHg) over the course of the intervention with no change in SBP in the control group (pre: 133.5 ± 6.6 mmHg vs. post: 131.9 ± 8.9 mmHg). Pearson’s correlation analyses revealed that changes in potential moderators of blood pressure including body weight, BMI, sodium intake and total kilocalories were each not associated with changes in SBP (r ≤ 0.14, P ≥ 0.5) or DBP (r ≤ 0.10, P ≥ 0.6) pre- to post-treatment. Chi-square demonstrated no significant differences in the number of participants per group (n = 4 DASH, n = 1 control) who indicated increasing physical activity during the intervention.
Conclusion:
DASH diet followed in a free-living environment significantly reduced SBP but not DBP. However, the changes in SBP and DBP were very similar to those noted in controlled clinical feeding evaluations of the DASH diet. Presently, none of the potential moderators of blood pressure that were assessed were independently associated with the observed changes in blood pressure which may be due to our small sample size or the possibility that it is the combined change in multiple factors that lead to reductions in blood pressure when following the DASH diet.
doi:10.4137/NMI.S3871
PMCID: PMC3736884  PMID: 23966788
hypertension; DASH; blood pressure; free-living environment
4.  The Relationship Between Preoperative and Primary Care Blood Pressure Among Veterans Presenting from Home for Surgery. Is There Evidence for Anesthesiologist-Initiated Blood Pressure Referral? 
Anesthesia and Analgesia  2011;114(1):205-214.
Background
American College of Cardiology/American Heart Association guidelines describe the perioperative evaluation as “a unique opportunity to identify patients with hypertension,” however factors such as anticipatory stress or medication noncompliance may induce a bias toward higher blood pressure, leaving clinicians unsure about how to interpret preoperative hypertension. Information describing the relationship between preoperative intake blood pressure and primary care measurements could help anesthesiologists make primary care referrals for improved blood pressure control in an evidence-based fashion. We hypothesized that the preoperative examination provides a useful basis for initiating primary care blood pressure referral.
Methods
We analyzed retrospective data on 2807 patients who arrived from home for surgery and who were subsequently evaluated within 6 months after surgery in the primary care center of the same institution. After descriptive analysis, we conducted multiple linear regression analysis to identify day-of-surgery (DOS) factors associated with subsequent primary care blood pressure. We calculated the sensitivity, specificity, and positive and negative predictive value of different blood pressure referral thresholds using both a single-measurement and a two-stage screen incorporating recent preoperative and DOS measurements for identifying patients with subsequently elevated primary care blood pressure.
Results
DOS systolic blood pressure (SBP) was higher than subsequent primary care SBP by a mean bias of 5.5mmHg (95% limits of agreement +43.8 to −32.8). DOS diastolic blood pressure (DBP) was higher than subsequent primary care DBP by a mean bias of 1.5mmHg (95% limits of agreement +13.0 to −10.0). Linear regression of DOS factors explained 19% of the variability in primary care SBP and 29% of the variability in DBP. Accounting for the observed bias, a two-stage SBP referral screen requiring preoperative clinic SBP≥140mmHg and DOS SBP≥146mmHg had 95.9% estimated specificity (95% CI 94.4 to 97.0) for identifying subsequent primary care SBP≥140mmHg and estimated sensitivity of 26.8% (95% CI 22.0 to 32.0). A similarly high specificity using a single DOS SBP required a threshold SBP≥160mmHg, for which estimated specificity was 95.2% (95% CI 94.2 to 96.1). For DBP, a presenting DOS DBP≥92mmHg had 95.7% specificity (95% CI 94.8 to 96.4) for subsequent primary care DBP≥90mmHg with a sensitivity of 18.8% (95% CI 14.4 to 24.0).
Conclusion
A small bias toward higher DOS blood pressures relative to subsequent primary care measurements was observed. DOS factors predicted only a small proportion of the observed variation. Accounting for the observed bias, a two-stage SBP threshold and a single-reading DBP threshold were highly specific though insensitive for identifying subsequent primary care blood pressure elevation.
doi:10.1213/ANE.0b013e318239c4c1
PMCID: PMC3282161  PMID: 22075017
5.  Pulse Pressure and Adverse Outcomes in Women: A Report From the Women’s Ischemia Syndrome Evaluation (WISE) 
American journal of hypertension  2008;21(11):1224-1230.
Background
Recent data suggest that brachial pulse pressure (PP) may be a better predictor of outcome than systolic or diastolic blood pressure (SBP/DBP). We sought to investigate the relative contributions of these indices to risk for adverse outcomes in women with suspected coronary artery disease (CAD) and myocardial ischemia.
Methods
Among 857 women referred for angiography for suspected myocardial ischemia, baseline evaluations were performed, and the women were followed for clinical outcome. Relationships between baseline characteristics, blood pressure components, and outcomes were evaluated. Separate multivariate stepwise Cox regression models for PP and SBP (expressed in 10 mm Hg increments) were constructed and included covariates significantly associated with adverse outcomes.
Results
After 5.2 years (mean), univariate testing identified higher PP associated with higher risk for cardiovascular (CV) mortality and adverse CV outcomes than SBP, DBP, or mean arterial pressure (MAP). Multivariate modeling identified both PP and SBP associated with adverse CV outcomes, but only PP was significantly associated with higher CV mortality. When both PP and SBP were included in the model, only PP remained an independent predictor of adverse outcomes for CV events.
Conclusions
In women with suspected CAD and myocardial ischemia, PP is a stronger predictor of adverse outcomes than SBP, DBP, or MAP with an 18% excess mortality risk for every 10 mm Hg increase in PP. Further investigations into pathophysiologic mechanisms and specific pharmacologic approaches to modifying this novel target are warranted.
doi:10.1038/ajh.2008.268
PMCID: PMC2586110  PMID: 18802432
6.  Blood Pressure Components and Decline in Kidney Function in Community-Living Older Adults: The Cardiovascular Health Study 
American Journal of Hypertension  2013;26(8):1037-1044.
BACKGROUND
Although hypertension contributes to kidney dysfunction in the general population, the contributions of elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) to kidney function decline in community-dwelling older adults are unknown.
METHODS
We used linear and logistic regression to examine the separate and combined associations of SBP, DBP, and PP at baseline with kidney function decline among 4,365 older adults in the Cardiovascular Health Study. We used cystatin C to estimate glomerular filtration rate on 3 occasions over 7 years of follow-up. We defined rapid decline ≥ 3ml/min/year.
RESULTS
Average age was 72.2 and mean (standard deviation) SBP, DBP, and PP were 135 (21), 71 (11), and 65 (18) mm Hg, respectively. SBP and PP, rather than DBP, were most significantly associated with kidney function decline. In adjusted linear models, each 10-mm Hg increment in SBP and PP was associated with 0.13ml/min/year (–0.19, –0.08, P < 0.001) and 0.15-ml/min/year faster decline (–0.21, –0.09, P < 0.001), respectively. Each 10-mm Hg increment in DBP was associated with a nonsignificant 0.10-ml/min/year faster decline (95% confidence interval, –0.20, 0.01). In adjusted logistic models, SBP had the strongest associations with rapid decline, with 14% increased hazard of rapid decline (95% confidence interval, 10% to 17%, P < 0.01) per 10mm Hg. In models combining BP components, only SBP consistently had independent associations with rapid decline.
CONCLUSIONS
Our findings suggest that elevated BP, particularly SBP, contributes to declining kidney function in older adults.
doi:10.1093/ajh/hpt067
PMCID: PMC3816322  PMID: 23709568
blood pressure; cystatin C; diastolic blood pressure; elderly; hypertension; kidney function; systolic blood pressure.
7.  Cardiorespiratory Biomarker Responses in Healthy Young Adults to Drastic Air Quality Changes Surrounding the 2008 Beijing Olympics 
Associations between air pollution and cardiorespiratory mortality and morbidity have been well established, but data to support biologic mechanisms underlying these associations are limited. We designed this study to examine several prominently hypothesized mechanisms by assessing Beijing residents’ biologic responses, at the biomarker level, to drastic changes in air quality brought about by unprecedented air pollution control measures implemented during the 2008 Beijing Olympics.
To test the hypothesis that changes in air pollution levels are associated with changes in biomarker levels reflecting inflammation, hemostasis, oxidative stress, and autonomic tone, we recruited and retained 125 nonsmoking adults (19 to 33 years old) free of cardiorespiratory and other chronic diseases. Using the combination of a quasi-experimental design and a panel-study approach, we measured biomarkers of autonomic dysfunction (heart rate [HR*] and heart rate variability [HRV]), of systemic inflammation and oxidative stress (plasma C-reactive protein [CRP], fibrinogen, blood cell counts and differentials, and urinary 8-hydroxy-2′-deoxyguanosine [8-OHdG]), of pulmonary inflammation and oxidative stress (fractional exhaled nitric oxide [FeNO], exhaled breath condensate [EBC] pH, EBC nitrate, EBC nitrite, EBC nitrite+nitrate [sum of the concentrations of nitrite and nitrate], and EBC 8-isoprostane), of hemostasis (platelet activation [plasma sCD62P and sCD40L], platelet aggregation, and von Willebrand factor [vWF]), and of blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). These biomarkers were measured on each subject twice before, twice during, and twice after the Beijing Olympics. For each subject, repeated measurements were separated by at least one week to avoid potential residual effects from a prior measurement. We measured a large suite of air pollutants (PM2.5 [particulate matter ≤ 2.5 μm in aerodynamic diameter] and constituents, sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], and ozone [O3]) throughout the study at a central Beijing site near the residences and workplaces of the subjects on a daily basis. Total particle number (TPN) was also measured at a separate site. We used a time-series analysis to assess changes in pollutant concentration by period (pre-, during-, and post-Olympics periods). We used mixed-effects models to assess changes in biomarker levels by period and to estimate changes associated with increases in pollutant concentrations, controlling for ambient temperature, relative humidity (RH), sex, and the day of the week of the biomarker measurements. We conducted sensitivity analyses to assess the impact of potential temporal confounding and exposure misclassification.
We observed reductions in mean concentrations for all measured pollutants except O3 from the pre-Olympics period to the during-Olympics period. On average, elemental carbon (EC) changed by −36%, TPN by −22%, SO2 by −60%, CO by −48%, and NO2 by −43% (P < 0.05 for all these pollutants). Reductions were observed in mean concentrations of PM2.5 (by −27%), sulfate (SO42−) (by −13%), and organic carbon (OC) (by −23%); however, these values were not statistically significant. Both 24-hour averages and 1-hour maximums of O3 increased (by 20% and 17%, respectively) from the pre-Olympics to the during-Olympics period. In the post-Olympics period after the pollution control measures were relaxed, mean concentrations of most pollutants (with the exception of SO42− and O3) increased to levels similar to or higher than pre-Olympics levels.
Concomitantly and consistent with the hypothesis, we observed, from the pre-Olympics to the during-Olympics period, statistically significant (P ≤ 0.05) or marginally significant (0.05 < P < 0.1) decreases in HR (−1 bpm or −1.7% [95% CI, −3.4 to −0.1]), SBP (−1.6 mmHg or − 1.8% [95% CI, −3.9 to 0.4]), 8-OHdG (−58.3% [95% CI, −72.5 to −36.7]), FeNO (−60.3% [95% CI, −66.0 to −53.6]), EBC nitrite (−30.0% [95% CI, −39.3 to −19.3]), EBC nitrate (−21.5% [95% CI, −35.5 to −4.5]), EBC nitrite+nitrate (−17.6% [95% CI, −28.4 to −5.1]), EBC hydrogen ions (−46% [calculated from EBC pH], or +3.5% in EBC pH [95% CI, 2.2 to 4.9]), sCD62P (−34% [95% CI, −38.4 to −29.2]), sCD40L (−5.7% [95% CI, −10.5 to −0.7]), and vWF (−13.1% [95% CI, −18.6 to −7.5]). Moreover, the percentages of above-detection values out of all observations were significantly lower for plasma CRP and EBC 8-isoprostane in the during-Olympics period compared with the pre-Olympics period. In the post-Olympics period, the levels of the following biomarkers reversed (increased, either with or without statistical significance) from those in the during-Olympics period: SBP (10.7% [95% CI, 2.8 to 18.6]), fibrinogen (4.3% [95% CI, −1.7 to 10.2), neutrophil count (4.7% [95% CI, −7.7 to 17.0]), 8-OHdG (315% [95% CI, 62.0 to 962]), FeNO (130% [95% CI, 62.5 to 225]), EBC nitrite (159% [95% CI, 71.8 to 292]), EBC nitrate (161% [95% CI, 48.0 to 362]), EBC nitrite+nitrate (124% [95% CI, 50.9 to 233]), EBC hydrogen ions (146% [calculated from EBC pH] or −4.8% in EBC pH [95% CI, −9.4 to −0.2]), sCD62P (33.7% [95% CI, 17.7 to 51.8]), and sCD40L (9.1% [95% CI, −3.7 to 23.5]).
Furthermore, these biomarkers also showed statistically significant associations with multiple pollutants across different lags after adjusting for meteorologic parameters. The associations were in the directions hypothesized and were consistent with the findings from the comparisons between periods, providing further evidence that the period effects were due to changes in air quality, independent of season and meteorologic conditions or other potential confounders. Contrary to our hypothesis, however, we observed increases in platelet aggregation, red blood cells (RBCs) and white blood cells (WBCs) associated with the during-Olympics period, as well as significant negative associations of these biomarkers with pollutant concentrations. We did not observe significant changes in any of the HRV indices and DBP by period. However, we observed associations between a few HRV indices and pollutant concentrations.
Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of pulmonary and systemic inflammation, oxidative stress, and hemostasis and in measures of cardiovascular physiology (HR and SBP) in healthy, young adults. These changes support the prominently hypothesized mechanistic pathways underlying the cardiorespiratory effects of air pollution.
PMCID: PMC4086245  PMID: 23646463
8.  Blood pressure standards for Saudi children and adolescents 
Annals of Saudi Medicine  2009;29(3):173-178.
BACKGROUND AND OBJECTIVES:
Blood pressure levels may vary in children because of genetic, ethnic and socioeconomic factors. To date, there have been no large national studies in Saudi Arabia on blood pressure in children. Therefore, we sought to establish representative blood pressure reference centiles for Saudi Arabian children and adolescents.
SUBJECTS AND METHODS:
We selected a sample of children and adolescents aged from birth to 18 years by multi-stage probability sampling of the Saudi population. The selected sample represented Saudi children from the whole country. Data were collected through a house-to-house survey of all selected households in all 13 regions in the country. Data were analyzed to study the distribution pattern of systolic (SBP) and diastolic blood pressure (DBP) and to develop reference values. The 90th percentile of SBP and DBP values for each age were compared with values from a Turkish and an American study.
RESULTS:
A total of 16 226 Saudi children and adolescents from birth to 18 years were studied. Blood pressure rose steadily with age in both boys and girls. The average annual increase in SBP was 1.66 mm Hg for boys and 1.44 mm Hg for girls. The average annual increase in DBP was 0.83 mm Hg for boys and 0.77 mm Hg for girls. DBP rose sharply in boys at the age of 18 years. Values for the 90th percentile of both SBP and DBP varied in Saudi children from their Turkish and American counterparts for all age groups.
CONCLUSION:
Blood pressure values in this study differed from those from other studies in developing countries and in the United States, indicating that comparison across studies is difficult and from that every population should use their own normal standards to define measured blood pressure levels in children.
doi:10.4103/0256-4947.51787
PMCID: PMC2813655  PMID: 19448364
9.  The Promise of Prevention: The Effects of Four Preventable Risk Factors on National Life Expectancy and Life Expectancy Disparities by Race and County in the United States 
PLoS Medicine  2010;7(3):e1000248.
Majid Ezzati and colleagues examine the contribution of a set of risk factors (smoking, high blood pressure, elevated blood glucose, and adiposity) to socioeconomic disparities in life expectancy in the US population.
Background
There has been substantial research on psychosocial and health care determinants of health disparities in the United States (US) but less on the role of modifiable risk factors. We estimated the effects of smoking, high blood pressure, elevated blood glucose, and adiposity on national life expectancy and on disparities in life expectancy and disease-specific mortality among eight subgroups of the US population (the “Eight Americas”) defined on the basis of race and the location and socioeconomic characteristics of county of residence, in 2005.
Methods and Findings
We combined data from the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System to estimate unbiased risk factor levels for the Eight Americas. We used data from the National Center for Health Statistics to estimate age–sex–disease-specific number of deaths in 2005. We used systematic reviews and meta-analyses of epidemiologic studies to obtain risk factor effect sizes for disease-specific mortality. We used epidemiologic methods for multiple risk factors to estimate the effects of current exposure to these risk factors on death rates, and life table methods to estimate effects on life expectancy. Asians had the lowest mean body mass index, fasting plasma glucose, and smoking; whites had the lowest systolic blood pressure (SBP). SBP was highest in blacks, especially in the rural South—5–7 mmHg higher than whites. The other three risk factors were highest in Western Native Americans, Southern low-income rural blacks, and/or low-income whites in Appalachia and the Mississippi Valley. Nationally, these four risk factors reduced life expectancy at birth in 2005 by an estimated 4.9 y in men and 4.1 y in women. Life expectancy effects were smallest in Asians (M, 4.1 y; F, 3.6 y) and largest in Southern rural blacks (M, 6.7 y; F, 5.7 y). Standard deviation of life expectancies in the Eight Americas would decline by 0.50 y (18%) in men and 0.45 y (21%) in women if these risks had been reduced to optimal levels. Disparities in the probabilities of dying from cardiovascular diseases and diabetes at different ages would decline by 69%–80%; the corresponding reduction for probabilities of dying from cancers would be 29%–50%. Individually, smoking and high blood pressure had the largest effect on life expectancy disparities.
Conclusions
Disparities in smoking, blood pressure, blood glucose, and adiposity explain a significant proportion of disparities in mortality from cardiovascular diseases and cancers, and some of the life expectancy disparities in the US.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Life expectancy (a measure of longevity and premature death) and overall health have increased steadily in the United States over recent years. New drugs, new medical technologies, and better disease prevention have all helped Americans to lead longer, healthier lives. However, even now, some Americans live much longer and much healthier lives than others. Health disparities—differences in how often certain diseases occur and cause death in groups of people classified according to their ethnicity, geographical location, sex, or age—are extremely large and persistent in the US. On average, black men and women in the US live 6.3 and 4.5 years less, respectively, than their white counterparts; the gap between life expectancy in the US counties with the lowest and highest life expectancies is 18.4 years for men and 14.3 years for women. Disparities in deaths (mortality) from chronic diseases such as cardiovascular diseases (for example, heart attacks and stroke), cancers, and diabetes are known to be the main determinants of these life expectancy disparities.
Why Was This Study Done?
Preventable risk factors such as smoking, high blood pressure, excessive body fat (adiposity), and high blood sugar are responsible for many thousands of deaths from chronic diseases. Exposure to these risk factors varies widely by race, state of residence, and socioeconomic status. However, the effects of these observed disparities in exposure to modifiable risk factors on US life expectancy disparities have only been examined in selected groups of people and it is not known how multiple modifiable risk factors affect US health disparities. A better knowledge about how disparities in risk factor exposure contribute to health disparities is needed to ensure that prevention programs not only improve the average health status but also reduce health disparities. In this study, the researchers estimate the effects of smoking, high blood pressure, high blood sugar, and adiposity on US life expectancy and on disparities in life expectancy and disease-specific deaths among the “Eight Americas,” population groups defined by race and by the location and socioeconomic characteristics of their county of residence.
What Did the Researchers Do and Find?
The researchers extracted data on exposure to these risk factors from US national health surveys, information on deaths from different diseases in 2005 from the US National Center for Health Statistics, and estimates of how much each risk factor increases the risk of death from each disease from published studies. They then used modeling methods to estimate the effects of risk factor exposure on death rates and life expectancy. The Asian subgroup had the lowest adiposity, blood sugar, and smoking rates, they report, and the three white subgroups had the lowest blood pressure. Blood pressure was highest in the three black subgroups, whereas the other three risk factors were highest in Western Native Americans, Southern rural blacks, and whites living in Appalachia and the Mississippi Valley. The effects on life expectancy of these factors were smallest in Asians and largest in Southern rural blacks but, overall, these risk factors reduced the life expectancy for men and women born in 2005 by 4.9 and 4.1 years, respectively. Other calculations indicate that if these four risk factors were reduced to optimal levels, disparities among the subgroups in deaths from cardiovascular diseases and diabetes and from cancers would be reduced by up to 80% and 50%, respectively.
What Do These Findings Mean?
These findings suggest that disparities in smoking, blood pressure, blood sugar, and adiposity among US racial and geographical subgroups explain a substantial proportion of the disparities in deaths from cardiovascular diseases, diabetes, and cancers among these subgroups. The disparities in risk factor exposure also explain some of the disparities in life expectancy. The remaining disparities in deaths and life expectancy could be the result of preventable risk factors not included in this study—one of its limitations is that it does not consider the effect of dietary fat, alcohol use, and dietary salt, which are major contributors to different diseases. Thus, suggest the researchers, reduced exposure to preventable risk factors through the implementation of relevant policies and programs should reduce life expectancy and mortality disparities in the US and yield health benefits at a national scale.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000248.
The US Centers for Disease Control and Prevention, the US Office of Minority Health, and the US National Center on Minority Health and Health Disparities all provide information on health disparities in the US
MedlinePlus provides links to information on health disparities and on healthy living (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of healthy living
The American Heart Association and the American Cancer Society provide information on modifiable risk factors for patients and caregivers
Healthy People 2010 is a national framework designed to improve the health of people living in the US
The US National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS) collect information on risk factor exposures in the US
doi:10.1371/journal.pmed.1000248
PMCID: PMC2843596  PMID: 20351772
10.  Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: A sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients 
Objectives
The metabolic syndrome is a cluster of cardiovascular risk factors leading to an increased risk for the subsequent development of diabetes and cardiovascular morbidity and mortality. Blocking the renin-angiotensin system has been shown to prevent cardiovascular disease and delay the onset of diabetes. Irbesartan is an angiotensin receptor blocker (ARB) which has been shown to possess peroxisome proliferator-activated receptor gamma (PPARγ) activating properties, and to have a favorable metabolic profile. Current discussion is whether the addition of small doses of hydrochlorothiazide changes this profile. Therefore the efficacy, safety and metabolic profile of Irbesartan either as monotherapy or in combination therapy was assessed in patients with the metabolic syndrome in a large observational cohort in primary care.
Research design and methods
Multicenter, prospective, two-armed, post authorization study over 9 months in 14,200 patients with uncontrolled hypertension with and without the metabolic syndrome (doctors' diagnosis based on the Adult Treatment Panel III criteria 2001). Blood pressure was measured sphygmomanometrically and cardiovascular risk factors making up the criteria for the metabolic syndrome were assessed.
Main outcome measures
Systolic (SBP) and diastolic (DBP) blood pressure reduction, – response, and – normalization (systolic and diastolic), changes in fasting glucose, waist circumference (abdominal obesity), serum triglycerides and HDL cholesterol as well as the proportion of patients fulfilling the criteria for the metabolic syndrome. Number and nature of adverse events (AEs).
Results
After 9 month the use of Irbesartan in monotherapy resulted in a significant reduction of blood pressure (SBP: -26.3 ± 10.1 mmHg/DBP-13.0 ± 6.6 mmHg, both p < 0.0001) in patients with the metabolic syndrome. This was accompanied by a reduction in cardiovascular risk factors: HDL cholesterol (+3.6 ± 7.2 mg/dl in men, +3.8 ± 6.5 mg/dl in women, both p < 0.0001), serum triglycerides (-28.6 ± 52.1 mg/dl, p < 0.0001), fasting blood glucose (-8.4 ± 25.1 mg/dl, p < 0.0001) and waist circumference (-2.4 ± 11.9 cm in men, -1.2 ± 14.2 in women, both p < 0.0001) were significantly improved. Irbesartan combination therapy (12.5 mg HCTZ) in patients with the metabolic syndrome: blood pressure reduction (SBP: -27.5 ± 10.1 mmHg/DBP: -14.1 ± 6.6 mmHg, both p < 0.0001), improvement in HDL cholesterol (+4.0 ± 6.8 mg/dl in men, +3.4 ± 6.8 in women, both p < 0.0001), triglycerides (-34.1 ± 52.6 mg/dl, p < 0.0001), fasting blood glucose (-10.0 ± 24.7, p < 0.0001) and waist circumference (-3.2 ± 12.7 cm in men, -1.7 ± 14.4 in women, both p < 0.0001). Tolerability was excellent: only 0.6% of patients experienced an AE.
Conclusion
There was a significant improvement in blood pressure and metabolic risk factors as a result of Irbesartan treatment. There was no evidence of a difference between monotherapy and combination therapy with regard to the cardiovascular risk profile.
doi:10.1186/1475-2840-6-12
PMCID: PMC1853076  PMID: 17407587
11.  Relative Systemic Hypertension in Patients with Sickle Cell Disease is Associated with Risk of Pulmonary Hypertension and Renal Insufficiency 
American Journal of Hematology  2008;83(1):15-18.
We analyzed entry data from 163 adult hemoglobin SS and Sβ0 thalassemia patients enrolled in the prospective Sickle Cell Pulmonary Hypertension Screening Study and stratified their ECHO-determined tricuspid regurgitant jet velocity (TRV) and serum creatinine concentration according to three blood pressure categories. TRV was ≥2.5 m/sec in 27% of the patients with systolic blood pressure (SBP) <120 mm Hg and diastolic blood pressure (DBP) <70 mm Hg, in 37% with SBP 120–139 mm Hg or DBP 70–89 mm Hg, and in 93% with SBP 140 mm Hg or DBP 90 mm Hg or higher (P <0.0005 for trend). Serum creatinine concentration was 1.0 mg/dL or higher in 7% of patients with SBP <120 mm Hg and DBP <70 mm Hg, in 17% with SBP 120–139 mm Hg or DBP 70–89 mm Hg and 50% with SBP 140 mm Hg or DBP 90 mm Hg or higher (P <0.0005 for trend). Over two years of follow-up, there were trends for more frequent progression to elevated TRV (P = 0.073) or creatinine (P = 0.038) values according to the higher systemic blood pressure categories. Our findings suggest that systolic SBP 120–139 mm Hg or DBP 70–89 mm Hg defines a category of relative systemic hypertension in patients with sickle cell disease that is associated with increased risk for pulmonary hypertension and renal dysfunction. Whether antihypertensive and/or nitric oxide donor therapy in sickle cell disease patients with relative hypertension prevents these and other complications should be determined by clinical trials.
doi:10.1002/ajh.21016
PMCID: PMC3398810  PMID: 17696198
12.  Risk Stratification by Self-Measured Home Blood Pressure across Categories of Conventional Blood Pressure: A Participant-Level Meta-Analysis 
PLoS Medicine  2014;11(1):e1001591.
Jan Staessen and colleagues compare the risk of cardiovascular, cardiac, or cerebrovascular events in patients with elevated office blood pressure vs. self-measured home blood pressure.
Please see later in the article for the Editors' Summary
Background
The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP).
Methods and Findings
This meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, <120/<80; normal, 120–129/80–84; high-normal, 130–139/85–89; mild hypertension, 140–159/90–99; and severe hypertension, ≥160/≥100.
Over 8.3 y, 522 participants died, and 414, 225, and 194 had cardiovascular, cardiac, and cerebrovascular events, respectively. In participants with optimal or normal CBP, HRs for a composite cardiovascular end point associated with a 10-mm Hg higher systolic HBP were 1.28 (1.01–1.62) and 1.22 (1.00–1.49), respectively. At high-normal CBP and in mild hypertension, the HRs were 1.24 (1.03–1.49) and 1.20 (1.06–1.37), respectively, for all cardiovascular events and 1.33 (1.07–1.65) and 1.30 (1.09–1.56), respectively, for stroke. In severe hypertension, the HRs were not significant (p≥0.20). Among people with optimal, normal, and high-normal CBP, 67 (5.0%), 187 (18.4%), and 315 (30.3%), respectively, had masked hypertension (HBP≥130 mm Hg systolic or ≥85 mm Hg diastolic). Compared to true optimal CBP, masked hypertension was associated with a 2.3-fold (1.5–3.5) higher cardiovascular risk. A limitation was few data from low- and middle-income countries.
Conclusions
HBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased risk, in particular in the presence of masked hypertension. Randomized trials could help determine the best use of CBP vs. HBP in guiding BP management. Our study identified a novel indication for HBP, which, in view of its low cost and the increased availability of electronic communication, might be globally applicable, even in remote areas or in low-resource settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Globally, hypertension (high blood pressure) is the leading risk factor for cardiovascular disease and is responsible for 9.4 million deaths annually from heart attacks, stroke, and other cardiovascular diseases. Hypertension, which rarely has any symptoms, is diagnosed by measuring blood pressure, the force that blood circulating in the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic blood pressure) and lowest when the heart is refilling (diastolic blood pressure). European guidelines define optimal blood pressure as a systolic blood pressure of less than 120 millimeters of mercury (mm Hg) and a diastolic blood pressure of less than 80 mm Hg (a blood pressure of less than 120/80 mm Hg). Normal blood pressure, high-normal blood pressure, and mild hypertension are defined as blood pressures in the ranges 120–129/80–84 mm Hg, 130–139/85–89 mm Hg, and 140–159/90–99 mm Hg, respectively. A blood pressure of more than 160 mm Hg systolic or 100 mm Hg diastolic indicates severe hypertension. Many factors affect blood pressure; overweight people and individuals who eat salty or fatty food are at high risk of developing hypertension. Lifestyle changes and/or antihypertensive drugs can be used to control hypertension.
Why Was This Study Done?
The current guidelines for the diagnosis and management of hypertension recommend risk stratification based on conventionally measured blood pressure (CBP, the average of two consecutive measurements made at a clinic). However, self-measured home blood pressure (HBP) more accurately predicts outcomes because multiple HBP readings are taken and because HBP measurement avoids the “white-coat effect”—some individuals have a raised blood pressure in a clinical setting but not at home. Could risk stratification across increasing categories of CBP be refined through the use of self-measured HBP, particularly at CBP levels assumed to be associated with no or only mildly increased risk? Here, the researchers undertake a participant-level meta-analysis (a study that uses statistical approaches to pool results from individual participants in several independent studies) to answer this question.
What Did the Researchers Do and Find?
The researchers included 5,008 individuals recruited from five populations and enrolled in the International Database of Home Blood Pressure in Relation to Cardiovascular Outcome (IDHOCO) in their meta-analysis. CBP readings were available for all the participants, who measured their HBP using an oscillometric device (an electronic device for measuring blood pressure). The researchers used information on fatal and nonfatal cardiovascular, cardiac, and cerebrovascular (stroke) events to calculate the hazard ratios (HRs, indicators of increased risk) associated with a 10-mm Hg increase in systolic HBP across standard CBP categories. In participants with optimal CBP, an increase in systolic HBP of 10-mm Hg increased the risk of any cardiovascular event by nearly 30% (an HR of 1.28). Similar HRs were associated with a 10-mm Hg increase in systolic HBP for all cardiovascular events among people with normal and high-normal CBP and with mild hypertension, but for people with severe hypertension, systolic HBP did not significantly add to the prediction of any end point. Among people with optimal, normal, and high-normal CBP, 5%, 18.4%, and 30.4%, respectively, had a HBP of 130/85 or higher (“masked hypertension,” a higher blood pressure in daily life than in a clinical setting). Finally, compared to individuals with optimal CBP without masked hypertension, individuals with masked hypertension had more than double the risk of cardiovascular disease.
What Do These Findings Mean?
These findings indicate that HBP measurements, particularly in individuals with masked hypertension, refine risk stratification at CBP levels assumed to be associated with no or mildly elevated risk of cardiovascular disease. That is, HBP measurements can improve the prediction of cardiovascular complications or death among individuals with optimal, normal, and high-normal CBP but not among individuals with severe hypertension. Clinical trials are needed to test whether the identification and treatment of masked hypertension leads to a reduction of cardiovascular complications and is cost-effective compared to the current standard of care, which does not include HBP measurements and does not treat people with normal or high-normal CBP. Until then, these findings provide support for including HBP monitoring in primary prevention strategies for cardiovascular disease among individuals at risk for masked hypertension (for example, people with diabetes), and for carrying out HBP monitoring in people with a normal CBP but unexplained signs of hypertensive target organ damage.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001591.
This study is further discussed in a PLOS Medicine Perspective by Mark Caulfield
The US National Heart, Lung, and Blood Institute has patient information about high blood pressure (in English and Spanish) and a guide to lowering high blood pressure that includes personal stories
The American Heart Association provides information on high blood pressure and on cardiovascular diseases (in several languages); it also provides personal stories about dealing with high blood pressure
The UK National Health Service Choices website provides detailed information for patients about hypertension (including a personal story) and about cardiovascular disease
The World Health Organization provides information on cardiovascular disease and controlling blood pressure; its A Global Brief on Hypertension was published on World Health Day 2013
The UK charity Blood Pressure UK provides information about white-coat hypertension and about home blood pressure monitoring
MedlinePlus provides links to further information about high blood pressure, heart disease, and stroke (in English and Spanish)
doi:10.1371/journal.pmed.1001591
PMCID: PMC3897370  PMID: 24465187
13.  Genome-Wide Linkage Screen for Systolic Blood Pressure in the Veterans Administration Genetic Epidemiology Study (VAGES) of Mexican-Americans and Confirmation of a Major Susceptibility Locus on Chromosome 6q14.1 
Human Heredity  2011;71(1):1-10.
Objective
Hypertension or high blood pressure is a strong correlate of diseases such as obesity and type 2 diabetes. We conducted a genome-wide linkage screen to identify susceptibility genes influencing systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Mexican-Americans from the Veterans Administration Genetic Epidemiology Study (VAGES).
Methods
Using data from 1,089 individuals distributed across 266 families, we performed a multipoint linkage analysis to localize susceptibility loci for SBP and DBP by applying two models. In model 1, we added a sensible constant to the observed BP values in treated subjects [Tobin et al.; Stat Med 2005;24:2911–2935] to account for antihypertensive use (i.e. 15 and 10 mm Hg to SBP and DBP values, respectively). In model 2, we fixed values of 140 mm Hg for SBP and 90 mm Hg for DBP, if the treated values were less than the standard referenced treatment thresholds of 140/90 mm Hg for hypertensive status. However, if the observed treated BP values were found to be above these standard treatment thresholds, the actual observed treated BP values were retained in order not to reduce them by substitution of the treatment threshold values.
Results
The multipoint linkage analysis revealed strong linkage signals for SBP compared with DBP. The strongest evidence for linkage of SBP (model 1, LOD = 5.0; model 2, LOD = 3.6) was found on chromosome 6q14.1 near the marker D6S1031 (89 cM) in both models. In addition, some evidence for SBP linkage occurred on chromosomes 1q, 4p, and 16p. Most importantly, our major SBP linkage finding on chromosome 6q near marker D6S1031 was independently confirmed in a Caucasian population (LOD = 3.3). In summary, our study found evidence for a major locus on chromosome 6q influencing SBP levels in Mexican-Americans.
doi:10.1159/000323143
PMCID: PMC3152483  PMID: 21293138
Hypertension; Linkage; Antihypertensive medication; Genetic location; Heritability
14.  Increasing blood pressure and its associated factors in Canadian children and adolescents from the Canadian Health Measures Survey 
BMC Public Health  2012;12:388.
Background
Canada is facing a childhood obesity epidemic. Elevated blood pressure (BP) is a major complication of obesity. Reports on the impact of excess adiposity on BP in children and adolescents have varied significantly across studies. We evaluated the independent effects of obesity, physical activity, family history of hypertension, and socioeconomic status on BP in a nationally representative sample of children and adolescents.
Methods
We analysed cross-sectional data for 1850 children aged 6 to 17 years who participated in the Canadian Health Measures Survey, Cycle 1, 2007–2009. Systolic BP (SBP) and diastolic BP (DBP) were age-, sex-, and height-adjusted to z-scores (SBPZ and DBPZ). Body mass index (BMI) z-scores were calculated based on World Health Organization growth standards. Multivariate linear regression was used to evaluate the independent effects of relevant variables on SBPZ and DBPZ.
Results
For most age/sex groups, obesity was positively associated with SBP. Being obese was associated with higher DBP in adolescent boys only. The BP effect of obesity showed earlier in young girls than boys. Obese adolescents were estimated to have an average 7.6 mmHg higher SBP than normal weight adolescents. BMI had the strongest effect on BP among obese children and adolescents. Moderately active adolescent boys had higher SBP (3.9 mmHg) and DBP (4.9 mmHg) than physically active boys. Family history of hypertension showed effects on SBP and DBP in younger girls and adolescent boys. Both family income and parent education demonstrated independent associations with BP in young children.
Conclusions
Our findings demonstrate the early impact of excess adiposity, insufficient physical activity, family history of hypertension, and socioeconomic inequalities on BP. Early interventions to reduce childhood obesity can, among other things, reduce exposure to prolonged BP elevation and the future risk of cardiovascular disease.
doi:10.1186/1471-2458-12-388
PMCID: PMC3395567  PMID: 22642714
15.  Dysglycemia induces abnormal circadian blood pressure variability 
Background
Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).
Hypothesis
Systemic inflammation and glycemia influence circadian blood pressure variability.
Methods
Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP) and heart rate (HR) were recorded by telemetry every 5 minutes during both sleep (day) and active (night) periods. Pulse pressure (PP) was calculated (PP = SBP-DBP).
Results
[mean(SEM)]: The AD fed group displayed significant increase in body weight (after 90 days; p < 0.01). Fasting glucose, adipokine (leptin and adiponectin) concentrations significantly increased (at 90 and 172 days; all p < 0.05), along with a trend for increased concentrations of systemic pro-inflammatory cytokines (MCP-1 and TNF-α) on day 90. The AD fed group, with significantly higher FG, also exhibited significantly elevated circadian (24-hour) overall mean SBP, DBP, PP and HR (all p < 0.05).
Conclusion
These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system) which generate abnormal CBPV.
doi:10.1186/1475-2840-10-104
PMCID: PMC3247849  PMID: 22108527
caloric excess; adipose tissue dysfunction; insulin resistance; renin-aldosterone-angiotensin system; circadian blood pressure variability; adipokines; leptin; adiponectin; pro-inflammatory cytokines; MCP-1; TNF-α; early CVD risk
16.  Blood Pressure in Relation to Age and Frailty 
Background and Purpose
On average, systolic blood pressure (SBP) rises with age, while diastolic blood pressure (DBP) increases to age 50 and then declines. As elevated blood pressure is associated with cardiovascular disease and mortality, it also might be linked to frailty. We assessed the association between blood pressure, age, and frailty in a representative population-based cohort.
Methods
Individuals from the second clinical examination of the Canadian Study of Health and Aging (n = 2305, all 70+ years) were separated into four groups: history of hypertension ± antihypertensive medication, and no history of hypertension ± antihypertensive medication. Frailty was quantified as deficits accumulated in a frailty index (FI).
Results
SBP and DBP changed little in relation to age, except in untreated hypertension, where SBP declined in individuals >85 years. In contrast, SBP declined in all groups up to an FI of 0.55, and then rose sharply. DBP changed little in relation to FI. The slope of the line relating FI and age was highest in untreated individuals without a history of hypertension, indicating the highest physiological reserve.
Conclusions
SBP declined as frailty increased in older adults, except at the highest FI levels. SBP and age had little or no relationship.
PMCID: PMC3516342  PMID: 23251303
aging; hypertension; frailty
17.  The power combination of blood-pressure parameters to predict the incidence of plaque formation in carotid arteries in elderly 
Hypertension is considered as one of the major risk factors of atherosclerosis, especially for carotid artery plaque, which is a sign for cardiovascular incapacity and cerebral infarction. As adult age, systolic blood pressure (SBP or S) tends to rise and diastolic blood pressure (DBP or D) tends to fall, thus the pulse pressure (PP) will increase. The vascular injury was directly proportional to the level of SBP, and inversely proportional to DBP. But so far, studies of the vascular injury based on SBP and DBP measurement were mostly qualitative. The exact contribution of each parameter to the vascular injury has not been quantitatively identified. In this study, we employed a mathematical model to predict the risk for plaques of carotid arteries in aged people and combined the SBP, DBP and heart rate (HR) to perform a quantitative analysis. We analyzed 1672 males who were over 60-year-old and hospitalized due to atherosclerosis-related diseases and received a 24-h arterial blood pressure monitoring (ABPM) examination. These patients were divided into 19 subgroups using the ABPM data, 24-h average SBP, DBP and HR as variables based on the ascending order of the magnitude of each element. We developed a new index, namely the dynamic level (DL) which correlated best with the plaque formation of carotid arteries among all the well-established indexes for blood pressure. We demonstrated that index DL has better correlation to plaques incidence tendency (p < 0.0001) when compared to either SBP (P < 0.05) or PP (P < 0.001) alone. The risk on incidence of the plaques of carotid arteries has positive correlation with first power of SBP and -0.8 power of DBP. This model can be used clinically to predict the occurrence of plaque formation.
PMCID: PMC3703117  PMID: 23844270
Blood pressure parameters; the plaques of carotid arteries; mathematical method; vascular injury
18.  Effects of simvastatin on blood pressure in hypercholesterolemic patients: An open-label study in patients with hypertension or normotension 
Background
Simvastatin has been reported to improve endotheliumdependent vascular relaxation in patients with hypercholesterolemia. The consequent decrease in arterial stiffness might be associated with a decrease in blood pressure (BP).
Objective
The aim of this study was to determine whether simvastatin 20 and 40 mg/d have an effect on systolic and diastolic blood pressure (SBP and DBP, respectively) in patients with hypercholesterolemia, and, if so, whether the effect is dose dependent and/or is related to the changes in the serum lipid profile.
Methods
This 6-month, open-label study was conducted at the Lipid Clinics of the Department of Internal Medicine, University of Milan, Maggiore Hospital IRCCS, and of the Department of Internal Medicine 1, G. Salvini Hospital, Garbagnate Milanese (Milan, Italy). Patients aged 18 to 80 years with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet for >2 months before the study were enrolled. Patients at high risk for cardiovascular disease (CVD), according to the National Cholesterol Education Program Adult Treatment Panel II guidelines, were given simvastatin 20 mg (tablet) QD for 3 months, and those at low risk for CVD continued with diet only for 3 months (controls). Efficacy variables included body weight, SBP, DBP, and serum lipid levels (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C], and triglycerides [TG]). At 3 months, patients in the simvastatin + diet group who reached their therapeutic goal continued to receive simvastatin 20 mg/d for 3 additional months. In simvastatintreated patients who were normotensive at baseline or who became normotensive at 3 months but who did not reach the therapeutic goal, the simvastatin dosage was increased to 40 mg/d. Patients in both groups who remained hypertensive at 3 months were switched to hypotensive therapy. In the diet-only group, patients who were formerly normotensive or who became normotensive at 3 months but who did not reach their therapeutic goal continued with diet only or started lipid-lowering therapy. All other patients in the diet-only group continued to be treated with diet only, for 3 additional months. Efficacy variables were measured again at 6 months. Tolerability of simvastatin was assessed at each visit using patient interview and measurement of serum aminotransferase and creatine phosphokinase levels.
Results
The study population comprised 222 patients (132 women, 90 men; mean [SEM] age, 53.9 [0.95] years [range, 23–76 years]); 115 high-risk patients (57 with untreated stage 1 hypertension) were assigned to the simvastatin + diet group, and 107 low-risk patients (29 with untreated stage 1 hypertension) were assigned to the diet-only group. In the simvastatin group, after 3 months of therapy, mean SBP was decreased by 3.9 (1.49) mm Hg (change, −2.9%), mean DBP decreased by 3.0 (0.87) mm Hg (change, −3.7%), mean TC decreased by 90.6 (3.98) mg/dL (change, −27.0%), mean LDL-C decreased by 88.9 (3.88) mg/dL (change, −35.6%), and mean TG decreased by 26.3 (7.34) mg/dL (change, −15.8%) (all, P < 0.001). Mean HDL-C increased by 3.6 (1.16) mg/dL (change, 6.9%; P < 0.001). The BP-lowering effect was found only in patients with hypertension at baseline (n = 57); in these patients, mean SBP decreased by 7.2 (2.44) mm Hg (change, −4.8%; P < 0.005 vs baseline) and DBP decreased by 4.8 (1.29) mm Hg (change, −5.6%; P < 0.001 vs baseline). Also in the simvastatin group, 26 patients (22.6%) achieved their target SBP/DBP. In patients with normotension at baseline (n = 58), neither SBP nor DBP was changed significantly (changes, −0.8 [1.65] and −1.4 [1.15] mm Hg, respectively [−0.6% and −1.8%, respectively]). The changes in serum lipid levels were similar between hypertensive and normotensive patients in the simvastatin group. Forty-one patients (18 hypertensive and 23 normotensive at baseline) were treated with simvastatin 40 mg/d plus diet between months 3 and 6. At 6 months, no further significant decrease was observed in mean BP. In contrast, the expected dose-dependent response was observed for TC and LDL-C levels. In the diet-only group, no significant changes occurred in BP or serum lipid levels. Changes in BP, TC, LDL-C, TG, and HDL-C were significantly greater in the simvastatin + diet group than in the diet-only group (all, P < 0.001). Body weight did not change significantly in either group.
Conclusions
In this group of patients with hypercholesterolemia, the starting dosage of simvastatin (20 mg/d) was associated with reductions in SBP and DBP within 3 months of treatment in patients with hypertension, and this effect was independent of the lipid-lowering properties of the drug. Although the decrease in BP was modest, it is likely clinically relevant. Further studies on this topic are advisable.
doi:10.1016/S0011-393X(04)80057-2
PMCID: PMC3964554  PMID: 24672080
19.  Intradialytic Blood Pressure Variability Is Associated With Increased All-Cause and Cardiovascular Mortality in Patients Treated With Long-term Hemodialysis 
Background
Blood pressure is known to fluctuate widely during hemodialysis; however, little is known about the association between intradialytic blood pressure variability and outcomes.
Study Design
Retrospective observational cohort
Setting & Participants
A random sample of 6,393 adult, thrice-weekly, in-center, maintenance hemodialysis patients dialyzing at 1,026 dialysis units within a single large dialysis organization.
Predictor
Intradialytic systolic blood pressure (SBP) variability. This was calculated using a mixed linear effects model. Peri-dialytic SBP phenomena were defined as starting SBP (regression intercept), systematic change in SBP over the course of dialysis (2 regression slopes), and random intradialytic SBP variability (absolute regression residual).
Outcomes
All-cause and cardiovascular mortality.
Measurements
SBPs (n=631,922) measured during hemodialysis treatments (n=78,961) over the first 30 days in study. Outcome data were obtained from the dialysis unit electronic medical record and were considered beginning on day 31.
Results
High (ie, greater than the median) versus low SBP variability was associated with a greater risk of all-cause mortality (adjusted HR, 1.26; 95% CI, 1.08–1.47). The association between high SBP variability and cardiovascular mortality was even more potent (adjusted HR, 1.32; 85% CI, 1.01–1.72). A dose response trend was observed across quartiles of SBP variability for both all-cause (p=0.001) and cardiovascular (p=0.04) mortality.
Limitations
Inclusion of subjects from a single large dialysis organization, over-representation of African Americans and patients with diabetes and heart failure, and lack of standardized SBP measurements.
Conclusions
Greater intradialytic SBP variability is independently associated with increased all-cause and cardiovascular mortality. Further prospective studies are needed to confirm findings and identify means of reducing SBP variability to facilitate randomized study.
doi:10.1053/j.ajkd.2012.12.023
PMCID: PMC3660473  PMID: 23474007
20.  The Role of Blood Pressure Variability in the Development of Nephropathy in Type 1 Diabetes 
Diabetes Care  2010;33(11):2442-2447.
OBJECTIVE
Increases in blood pressure and visit-to-visit variability have both been found to independently increase the likelihood of cardiovascular events in nondiabetic individuals. This study has investigated whether each may also influence the development of microvascular complications in type 1 diabetes by examining data from the Diabetes Control and Complications Trial (DCCT).
RESEARCH DESIGN AND METHODS
Using binary longitudinal multiple logistic regression, mean systolic (SBP) and diastolic (DBP) blood pressure as well as annual visit-to-visit variability (SD.SBP and SD.DBP, respectively) was related to the risk of the development/progression of nephropathy and retinopathy in initially normotensive subjects who did not become pregnant during the DCCT.
RESULTS
Mean SBP and SD.SBP were independently predictive of albuminuria (odds ratio 1.005 [95% CI 1.002–1.008], P < 0.001 and 1.093 [1.069–1.117], P < 0.001, respectively, for 1 mmHg change), although SBP variability did not add to mean SBP in predicting retinopathy (0.999 [0.985–1.013], P = 0.93). DBP variability was also independently predictive of nephropathy (1.102 [1.068–1.137], P < 0.001) and not of retinopathy (0.991 [0.971–1.010], P = 0.37). Mean SBP was poorly related to SD.SBP (r2 < 0.01) as was mean DBP with SD. DBP (r2 < 0.01).
CONCLUSIONS
Visit-to-visit variability in blood pressure consistently independently added to mean blood pressure in predicting the risk of nephropathy, but not retinopathy, in the DCCT. This observation could have implications for the management and treatment of blood pressure in patients with type 1 diabetes.
doi:10.2337/dc10-1000
PMCID: PMC2963509  PMID: 20798339
21.  Sex Differences in the Association of Childhood Socioeconomic Status with Adult Blood Pressure Change: The CARDIA Study 
Psychosomatic medicine  2012;74(7):728-735.
Objective
To examine sex differences in the relation of childhood socioeconomic status (CSES) to systolic (SBP) and diastolic (DBP) blood pressure trajectories during 15-years spanning young (30 ± 3 years) and middle (45±3 years) adulthood, independent of adult SES.
Method
4077 adult participants reported father’s and mother’s educational attainments at study enrollment (Year 0), and own educational attainment at enrollment and at all follow-up exams. Resting BP also was measured at all exams. Data from exam Years 5 (when participant mean age=30± 3 years), 7, 10, 15, and 20 are examined here. Associations of own adult [Year 5], mother’s, and father’s educations with 15-year BP trajectories were examined in separate multilevel models. Fully controlled models included time-invariant covariates (age, sex, race, recruitment center), and time-varying covariates that were measured at each exam (marital status, body mass, cholesterol, oral contraceptives/hormones, antihypertensives). Parental education analyses controlled for own education.
Results
When examined without covariates, higher education -- own (SBP γ=−0.03, DBP γ= −0.03), mother’s (SBP γ= −0.02, DBP γ= −0.02), and father’s (SBP γ= −0.02, DBP γ= −0.01) -- were associated with attenuated 15-year increases in BP (p<0.001). Associations of own (but not either parent’s) education with BP trajectories remained independent of standard controls. Sex moderated the apparent null effects of parental education, such that higher parental education–especially mother’s, predicted attenuated BP trajectories independent of standard covariates among women (SBP γ= −.02, p=.02; DBP γ= −.01, p=0.04) but not men (SBP γ=0.02, p=0.06; DBP γ=0.005, p=0.47; p-interaction SBP<0.001, p-interaction DBP=0.01).
Conclusion
CSES may influence women’s health independent of their own adult status.
doi:10.1097/PSY.0b013e31825e32e8
PMCID: PMC3434230  PMID: 22822232
blood pressure; childhood socioeconomic status; multilevel modeling; sex differences
22.  Association of blood lead to blood pressure in men aged 55 to 75 years: effect of selected social and biochemical confounders. NFR Study Group. 
Environmental Health Perspectives  1994;102(Suppl 9):107-111.
The association of blood lead (B-Pb) concentration to blood pressure was investigated in men aged 55 to 75 years living in the Rome area, who had no history of exposure to lead in the workplace and who participated between 1989 and 1990 in an epidemiologic survey for coronary heart disease (New Risk Factor Project). Of the 1856 individuals eligible for the study, 59 were excluded from analyses because not all relevant data were available; and 478 were excluded because they were treated for hypertension. In the remaining subjects (n = 1319) the median B-Pb concentration was 113 micrograms/l (range: 40-442 micrograms/l). Systolic blood pressure (SBP) averaged 140 +/- 18 (standard deviation) mm Hg (range 98-220) and diastolic blood pressure (DBP) 84 +/- 9 mm Hg (range 56-118). Median B-Pb values increased significantly from 111 micrograms/l in subjects with normal blood pressure (n = 668) to 113.5 micrograms/l in subjects with borderline high blood pressure (n = 373) and to 120 micrograms/l in subjects with increased blood pressure (n = 278). After log-normal conversion of B-Pb, the linear correlation coefficient between In[B-Pb(ug/l)] and both SBP and DBP was statistically significant (r = 0.1332, p < 0.001 and r = 0.0737, p = 0.007, respectively). The linear regression coefficient was 6.8 mm Hg/In(micrograms/l) for SBP and 1.8 mm Hg/In(microgram/l) for DBP. Multiple regression analyses revealed that, after correction for body mass index (BMI), age, heart rate, skinfold thickness, serum lipids, and glucose levels; blood lead was still a significant predictor of increased SBP and DBP.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1566780  PMID: 7698070
23.  The Relationship between the Blood Pressure Responses to Exercise following Training and Detraining Periods 
PLoS ONE  2014;9(9):e105755.
Background
Exercise training lowers blood pressure (BP), while BP increases and returns to pre-training values with detraining. Yet, there is considerable variability in these BP responses. We examined the relationship between the BP responses after 6 months of training followed by 2 weeks of detraining among the same people.
Methodology/Principal Findings
Subjects (n = 75) (X+SD, 50.2±10.6 yr) were sedentary, obese, and had prehypertension. They completed an aerobic (n = 34); resistance (n = 28); or aerobic + resistance or concurrent (n = 13) exercise training program. We calculated a metabolic syndrome z score (MetSz). Subjects were classified as BP responders (BP decreased) or non-responders (BP increased) to training and detraining. Linear and multivariable regression tested the BP response. Chi Square tested the frequency of responders and non-responders. The systolic BP (SBP, r = −0.474) and diastolic (DBP, r = −0.540) response to training negatively correlated with detraining (p<0.01), independent of modality (p>0.05). Exercise responders reduced SBP 11.5±7.8 (n = 29) and DBP 9.8±6.2 mmHg (n = 31); non-responders increased SBP 7.9.±10.9 (n = 46) and DBP 4.9±7.1 mmHg (n = 44) (p<0.001). We found 65.5% of SBP training responders were SBP detraining non-responders; while 60.9% of SBP training non-responders were SBP detraining responders (p = 0.034). Similarly, 80.6% of DBP training responders were DBP detraining non-responders; while 59.1% of DBP training non-responders were DBP detraining responders (p<0.001). The SBP detraining response (r = −0.521), resting SBP (r = −0.444), and MetSz (r = 0.288) explained 44.8% of the SBP training response (p<0.001). The DBP detraining response (r = −0.553), resting DBP (r = −0.450), and MetSz (r = 0.463) explained 60.1% of the DBP training response (p<0.001).
Conclusions/Significance
As expected most subjects that decreased BP after exercise training, increased BP after detraining. An unanticipated finding was most subjects that increased BP after exercise training, decreased BP after detraining. Reasons why the negative effects of exercise training on BP maybe reversed with detraining among some people should be explored further.
Trial Registration Information
ClinicalTrials.gov 1R01HL57354; 2003–2008; NCT00275145
doi:10.1371/journal.pone.0105755
PMCID: PMC4160181  PMID: 25208075
24.  Distribution of blood pressure in school going children in rural area of Wardha district, Maharashatra, India 
Annals of Pediatric Cardiology  2008;1(2):101-106.
Objectives:
To study the blood pressure of school going children in a rural area and its relationship with the anthropometric indices.
Methods:
A prospective, cross-sectional study was carried out from November 2006 to December 2007 in the school going children between the ages of 6–17 years from eight different schools in the rural areas of Wardha district. The height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded in both sexes followed by complete clinical examination with special emphasis on cardiovascular system. Hypertension (HT) was defined as SBP or DBP exceeding the 95th percentile for age, gender, and height on at least three separate occasions, 1–3 weeks apart. SPSS software was used to analyze the data. Coefficient correlation tests were employed to assess the relation between BP and anthropometric variables.
Results:
Of 2643 school children, 1227 were boys and 1416 girls with a male to female ratio of 1:1.16. In boys, SBP and DBP increased with age except a marginal decline in SBP at the age of 17 years (−0.09) and decrease in the DBP (−1.29) at 16 years of age. In girls, SBP and DBP also increased with age except at 11 years, wherein there was a mild decrease in SBP (−0.09) as well as the DBP (−0.24). Correlation coefficient analysis showed highly significant positive correlation of height with SBP and DBP. There was a significant correlation of SBP and DBP with the weight, and body mass index (BMI). The prevalence of HT was 5.75% (i.e., 3.25% for systolic HT and 2.49% for diastolic HT).
Conclusion:
We recommend that there is a need for checking BP to detect HT in children, so that remedial measures can be initiated as early as possible.
doi:10.4103/0974-2069.43874
PMCID: PMC2840757  PMID: 20300250
Blood pressure; children; hypertension; prevalence study
25.  Variability over time and correlates of cholesterol and blood pressure in systemic lupus erythematosus: a longitudinal cohort study 
Arthritis Research & Therapy  2010;12(3):R125.
Introduction
Total cholesterol (TC) and blood pressure (BP) are likely to take a dynamic course over time in patients with systemic lupus erythematosus (SLE). This would have important implications in terms of using single-point-in-time measurements of these variables to assess coronary artery disease (CAD) risk. The objective of this study was to describe and quantify variability over time of TC and BP among patients with SLE and to determine their correlates.
Methods
Patients in the Toronto lupus cohort who had two or more serial measurements of TC and systolic and diastolic BP (SBP and DBP) were included in the analysis. Variability over time was described in terms of the proportion of patients whose TC and BP profile fluctuated between normal and elevated (TC > 5.2 mmol/L; SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg), and also in terms of within- and between-patient variance quantified by using analysis of variance modeling. Generalized estimating equations (GEEs) were used to determine independent correlates of each of TC, SBP, and DBP, treated as continuous outcome variables.
Results
In total, 1,260 patients, comprising 26,267 measurements of each of TC, SBP, and DBP, were included. Mean ± SD number of measurements per patient was 20.8 ± 20. Mean ± SD time interval between measurements was 5.4 ± 9.7 months. Mean ± SD time interval from the start to the end of the study was 9.3 ± 8.5 years. Over time, 64.7% of patients varied between having normal and elevated cholesterol levels, whereas the status of 46.4% of patients varied between normotensive and hypertensive. By using analysis of variance (ANOVA), the within-patient percentage of total variance for each of TC, SBP, and DBP was 48.2%, 51.2%, and 63.9%, respectively. By using GEE, independent correlates of TC and BP included age, disease activity, and corticosteroids; antimalarial use was negatively correlated with TC (all P values < 0.0001).
Conclusions
TC and BP vary markedly over time in patients with SLE. This variability is due not only to lipid-lowering and antihypertensive medications, but also to disease- and treatment-related factors such as disease activity, corticosteroids, and antimalarials. The dynamic nature of TC and BP in SLE makes a compelling case for deriving summary measures that better capture cumulative exposure to these risk factors.
doi:10.1186/ar3063
PMCID: PMC2911919  PMID: 20591138

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