Hypertension is common and treatable but detection and control remain a major health challenge. This study sought to determine population trends in blood pressure and in the control of hypertension in the Minneapolis/St. Paul area (2010 population: 2.85 million) from 1980–2009.
Methods and Results
Surveys of risk factors were carried out every five years among randomly selected adults aged 25–74.
Data on hypertension knowledge and use of medications were collected by interview. Blood pressure was measured using standardized methods with hypertension defined as blood pressure ≥140 and/or 90 mmHg or controlled (<140 and/or 90mmHg) on medications.
Six surveys included 11,192 men and 12,795 women. Mean systolic blood pressure (SBP) fell from 124.9 mmHg in 1980–82 to 121.1 mmHg in 2007–09 for men (p<.0001) and for women from 120.1 mmHg to 114.7 mmHg (p<.0001). Similar trends for diastolic blood pressure wereobserved. Adults with uncontrolled blood pressure (≥140 and/or 90 mmHg) with or without medication fell from 20.3% to 5.8% (p<.001) for men and 13.1% to 2.7% (p<.0001) for women. Anti-hypertensive medication use rose to over 50% among all adults aged 55–74. Men (66%) and women (72%) with hypertension were treated and controlled by 2007–09. A majority of the decline in mean population blood pressure was the result of control with aggressive use of anti-hypertensive drugs. Stroke mortality in this population fell in parallel.
Hypertension detection and control in this community is among the highest observed in a US population and already exceeds Health People 2020 goals.
Hypertension; Blood Pressure; Stroke; Epidemiology
To explore associations between diabetes etiology (type 1 diabetes mellitus [T1DM] vs. T2DM) and glycemic control in the prediction of 5-year periodontal status change.
RESEARCH DESIGN AND METHODS
The Study of Health in Pomerania (SHIP) is a population-based stratified sample of German men and women. Healthy participants and those determined to have T2DM arose from the SHIP cohort, and T1DM participants were recruited from diabetes clinics in the catchment area that gave rise to SHIP. Dentate participants (n = 2,626; 53% women; 20–81 years of age) were included. Diabetes was determined via physician diagnosis and/or HbA1c ≥6.5% (uncontrolled diabetes >7.0%). Examiners blinded to diabetes status performed random half-mouth periodontal examinations, assessing probing depth (PD) and attachment loss (AL) (four sites/tooth) at baseline and follow-up. Participants were categorized into six groups as follows: 1) diabetes free (n = 2,280), 2) incident T2DM (n = 79), 3) controlled T2DM (n = 80), 4) uncontrolled T2DM (n = 72), 5) controlled T1DM (n = 43), and 6) uncontrolled T1DM (n = 72). In multivariable regressions, mean PD change (ΔMPD), mean AL change (ΔMAL), or incident tooth-loss values were regressed across the aforementioned diabetes categories.
Mean (SD) ΔMPD and ΔMAL values among all participants were −0.08 ± 0.5 mm and 0.08 ± 1.03 mm, respectively, and 34% lost one or more teeth. Relative to diabetes-free participants, those with uncontrolled T2DM experienced greater ΔMPD ± SE (P < 0.05), whereas participants with either uncontrolled T1DM or uncontrolled T2DM realized greater ΔMAL (P < 0.05). Uncontrolled T1DM and T2DM were both associated with an increased risk of future tooth loss (P < 0.05).
Diabetes control, but not etiology, was associated with future tooth loss and accelerated AL progression.
Inflammation is etiologically implicated in cardiometabolic diseases for which there are known racial/ethnic disparities. Prior studies suggest there may be an association between self-reported experiences of racial/ethnic discrimination and inflammation, particularly C-reactive protein (CRP). It is not known whether that association is influenced by race/ethnicity and gender. In separate hierarchical linear models with time-varying covariates we examined that association among 901 Black women, 614 Black men, 958 White women, and 863 White men in the Coronary Artery Risk Development in Young Adults (CARDIA) study of young adults in four US communities. Self-reported experiences of racial/ethnic discrimination were ascertained in 1992–93 and 2000–01. Inflammation was measured as log-transformed CRP in those years and 2005–06. All analyses were adjusted for blood pressure, plasma total cholesterol, triglycerides, homeostatic model assessment for insulin resistance (HOMA-IR), age, education, and community. Our findings extend prior research by suggesting that, broadly speaking, self-reported experiences of racial/ethnic discrimination are associated with inflammation; however, this association is complex and varies for Black and White women and men. Black women reporting 1 or 2 experiences of discrimination had higher levels of CRP compared to Black women reporting no experiences of discrimination (β = 0.141, SE = 0.062, P < 0.05). This association was not statistically significant among Black women reporting 3 or more experiences of discrimination and not independent of modifiable risks (smoking and obesity) in the final model. White women reporting 3 or more experiences of discrimination had significantly higher levels of CRP compared to White women reporting no experiences of discrimination independent of modifiable risks in the final model (β = 0.300, SE = 0.113, P < 0.01). The association between self-reported experiences of racial/ethnic discrimination and CRP was not statistically significant among Black and White men reporting 1 or 2 experiences of discrimination. Further research is needed.
USA; Racial/ethnic discrimination; Blacks; Whites; Inflammation; C-reactive protein; Hierarchical linear models; gender
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.
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.
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).
CSES may influence women’s health independent of their own adult status.
blood pressure; childhood socioeconomic status; multilevel modeling; sex differences
There are substantial variations of relative risks (RR) in smoking-related mortality by country and time. We hypothesized the RRs in smoking-related mortality might differ depending on serum concentrations of persistent organic pollutants (POPs). We evaluated the associations of cigarette smoking with total mortality in 610 elderly (aged ≥ 70 yr) (702 elderly for organochlorine pesticides [OCPs]) after stratification by serum concentration of POPs, in the National Health and Nutrition Examination Survey (NHANES) 1999-2004 followed through 2006. Summary measures of POPs subclasses showed significant or marginally significant interaction with cigarette smoking on the risk of total mortality. P values for interaction were 0.069 for polychlorinated dibenzo-p-dioxins (PCDDs), 0.008 for polychlorinated biphenyls (PCBs), and 0.024 for OCPs. The effect of smoking on total mortality showed different patterns according to the serum concentration of some POPs. Former or current smokers had 1.4 to 2.9 times higher mortality rates compared with never smokers among participants with higher serum concentrations of POPs (2nd or 3rd tertiles). However, when the level of PCBs or OCPs were low (1st tertile), there were little positive associations between smoking and mortality. Our study suggests that the background exposure to several POPs may be related to variability in smoking-related total mortality.
Smoking; Mortality; Persistent Organic Pollutants; Polychlorinated Biphenyls; Organochlorine Pesticides
High salt intake may affect left ventricular mass (LVM). We hypothesized that urinary sodium (UNa) and sodium / potassium ratio (UNa/K) are associated with LVM in a predominantly normotensive cohort young adults. The Coronary Artery Risk Development in Young Adults (CARDIA) study is a multicenter cohort of black and white men and women aged 30 ± 3.6 years at the time of baseline echocardiographic examination (1990–1991). Two-dimensionally guided M-mode LVM indexed to body size (gm/m2.7) was calculated and urinary sodium (UNa) and potassium (UK) excretion assessed (average of three 24-hour urinary samples, n=1,042). Linear and logistic regression analysis was used. Participants were 57% women, and 55% black. Only 4% were hypertensive. Mean±SD UNa, UK, and UNa/K ratio were 175.6±131.0 mmol/24hour, 56.4±46.3 mmol/24hour and 3.4±1.4, respectively. Participants in the highest vs. lowest UNa excretion quartile had the greatest LVM (37.5 vs. 34.0 g/m2.7, p<0.001). Adjusted for age, sex, education and race, LVM averaged 0.945gm/m2.7 higher per SD of UNa/K (p=0.001). The relationship between UNa/K and LVM persisted among 399 participants with repeat echocardiographic measures five years later. In logistic regression analysis adjusted for age, sex, education and race, each SD higher baseline UNa/K was associated with 23% and 38% greater chance of being in the highest quartile of LVM at baseline (OR 1.23; p=0.005) and five years later (OR 1.38; p=0.02). A higher sodium to potassium excretion ratio is significantly related to cardiac structure even among healthy young adults.
urinary sodium; urinary potassium; sodium / potassium ratio; left ventricular mass
Rationale: Our previous cross-sectional study showed that serum adiponectin is inversely associated with asthma among women. However, it is not known if serum adiponectin predicts future development of asthma or if asthma affects subsequent serum adiponectin concentrations among women.
Objectives: To determine longitudinal association between serum adiponectin and incident asthma among women.
Methods: We used data from examinations at Years 10, 15, and 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. In our primary analysis, the association of CARDIA Year 15 serum adiponectin concentration with Year 20 incident asthma was evaluated. In our secondary analysis, the converse direction, that is, the association of CARDIA Year 10 prevalent asthma with Year 15 serum adiponectin, was evaluated, using logistic regression techniques.
Measurements and Main Results: Our primary analysis included 1,450 women, mostly premenopausal. Multivariable analyses demonstrated that the lowest tertile of Year 15 serum adiponectin concentration (<7 mg/L) predicted significantly higher risk for incident asthma at Year 20 among women (odds ratio, 2.07; 95% confidence interval, 1.05, 4.10), and particularly among current smokers (interaction P = 0.051). Further, low serum adiponectin was more important than body mass index in predicting the risk for incident asthma among women. We also showed that the converse relationship was not true; that is, Year 10 prevalent asthma did not predict Year 15 serum adiponectin concentrations in women.
Conclusions: Serum adiponectin affects future risk for asthma in women and not vice versa. Measures that raise systemic adiponectin concentrations may lead to newer ways to prevent asthma among women, particularly among those who smoke.
incident asthma; obesity; adiponectin; adipokine; women
The value of metabolic syndrome (MetS) in childhood and adolescence and its stability into young adulthood have been questioned. This study compared the MetS in late childhood (mean age 13) versus a cluster score of the MetS components as predictors of young adult (mean age 22) cardiovascular risk.
Anthropometrics, blood pressure, lipid profile, and insulin resistance (insulin clamp) were obtained in 265 individuals at mean ages 13 and 22. MetS was defined dichotomously by current pediatric and adult criteria. The MetS cluster score used the average of deviates of the MetS components standardized to their means and standard deviations at mean age 13.
The MetS was rarely present at mean age 13 and did not predict MetS at mean age 22 but identified individuals who continued to have adverse levels of risk factors at mean age 22. In contrast to the standard MetS definition, the MetS cluster score tracked strongly and at mean age 22 was significantly higher in the individuals with MetS at mean age 13 (0.78 ± 0.71) than those without MetS at mean age 13 (0.09 ± 0.70, p<0.0001).
Although MetS at mean age 13, using the conventional definition, is not a reliable method for predicting MetS at mean age 22, it does predict adverse levels of cardiovascular risk factors. A cluster score, using the MetS components as continuous variables, is more reliable in predicting young adult risk from late childhood.
Metabolic Syndrome; Risk Factors; Obesity; Insulin Resistance; Children
Nighttime blood pressure (BP) dipping can be quantified as the ratio of mean nighttime (sleep) BP to mean daytime (awake) BP. People whose dipping ratio is 0.90 have been referred to as nondippers, and nondipping is associated with cardiovascular disease events. We examined the relationship between systolic nighttime BP dipping in young adults and presence of coronary artery calcium (CAC) 10-15 years later using data from the ambulatory BP monitoring substudy of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Among 239 participants with adequate measures of both nighttime and daytime readings and coronary artery calcium, the systolic BP dipping ratio ranged from 0.72 to 1.24 (mean 0.88, SD 0.06), and CAC was present 10 to 15 years later in 54 participants (22.6%). Compared to those whose systolic BP dipping ratio ranged from 0.88 to 0.92 (Quartile 3), the 57 participants (23.9%) with less pronounced or absent dipping (ratio 0.92 to 1.24, Quartile 4) had an unadjusted odds ratio of 4.08 (95% CI 1.48-11.2) for presence of CAC. The 60 participants (25.1%) with a more pronounced dipping (ratio 0.72 to 0.85, Quartile 1) also had greater odds for presence of CAC (OR 4.76; 95% CI 1.76-12.9). When modeled as a continuous predictor, a U-shaped relationship between systolic BP dipping ratio and future CAC was apparent, and persisted after adjustment for multiple potential confounders (p<0.001 for quadratic term). Both failure of systolic BP to dip sufficiently and “overdipping” during nighttime may be associated with future subclinical coronary atherosclerosis.
ambulatory blood pressure; diurnal blood pressure; blood pressure dipping; coronary artery calcium; subclinical atherosclerosis
Candidate gene association studies for peripheral artery disease (PAD), including subclinical disease assessed with the ankle-brachial index (ABI), have been limited by the modest number of genes examined. We conducted a two stage meta-analysis of ~50,000 SNPs across ~2100 candidate genes to identify genetic variants for ABI.
Methods and results
We studied subjects of European ancestry from 8 studies (n = 21,547, 55% women, mean age 44–73 years) and African American ancestry from 5 studies (n = 7267, 60% women, mean age 41–73 years) involved in the candidate gene association resource (CARe) consortium. In each ethnic group, additive genetic models were used (with each additional copy of the minor allele corresponding to the given beta) to test each SNP for association with continuous ABI (excluding ABI > 1.40) and PAD (defined as ABI < 0.90) using linear or logistic regression with adjustment for known PAD risk factors and population stratification. We then conducted a fixed-effects inverse-variance weighted meta-analyses considering a p < 2 × 10−6 to denote statistical significance.
In the European ancestry discovery meta-analyses, rs2171209 in SYTL3 (β = −0.007, p = 6.02 × 10−7) and rs290481 in TCF7L2 (β = −0.008, p = 7.01 × 10−7) were significantly associated with ABI. None of the SNP associations for PAD were significant, though a SNP in CYP2B6 (p = 4.99 × 10−5) was among the strongest associations. These 3 genes are linked to key PAD risk factors (lipoprotein(a), type 2 diabetes, and smoking behavior, respectively). We sought replication in 6 population-based and 3 clinical samples (n = 15,440) for rs290481 and rs2171209. However, in the replication stage (rs2171209, p = 0.75; rs290481, p = 0.19) and in the combined discovery and replication analysis the SNP–ABI associations were no longer significant (rs2171209, p = 1.14 × 10−3; rs290481, p = 8.88 × 10−5). In African Americans, none of the SNP associations for ABI or PAD achieved an experiment-wide level of significance.
Genetic determinants of ABI and PAD remain elusive. Follow-up of these preliminary findings may uncover important biology given the known gene-risk factor associations. New and more powerful approaches to PAD gene discovery are warranted.
Ankle brachial index; Peripheral artery disease; Genetics; Candidate gene array; Meta-analysis; Ethnicity
Background: Acetylcholinesterase (AChE) inhibitors are commonly used pesticides that can effect hemodynamic changes through increased cholinergic stimulation. Children of agricultural workers are likely to have paraoccupational exposures to pesticides, but the potential physiological impact of such exposures is unclear.
Objectives: We investigated whether secondary pesticide exposures were associated with blood pressure and heart rate among children living in agricultural Ecuadorian communities.
Methods: This cross-sectional study included 271 children 4–9 years of age [51% cohabited with one or more flower plantation workers (mean duration, 5.2 years)]. Erythrocyte AChE activity was measured using the EQM Test-mate system. Linear regression models were used to estimate associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate with AChE activity, living with flower workers, duration of cohabitation with a flower worker, number of flower workers in the child’s home, and number of practices that might increase children’s exposure to pesticides.
Results: Mean (± SD) AChE activity was 3.14 ± 0.49 U/mL. A 1-U/mL decrease in AChE activity was associated with a 2.86-mmHg decrease in SBP (95% CI: –5.20, –0.53) and a 2.89-mmHg decrease in DBP (95% CI: –5.00, –0.78), after adjustment for potential confounders. Children living with flower workers had lower SBP (–1.72 mmHg; 95% CI: –3.53, 0.08) than other children, and practices that might increase exposure also were associated with lower SBP. No significant associations were found between exposures and heart rate.
Conclusions: Our findings suggest that subclinical secondary exposures to pesticides may affect vascular reactivity in children. Additional research is needed to confirm these findings.
acetylcholinesterase; AChE; agricultural communities; agriculture; blood pressure; children; Ecuador; epidemiology; pesticides; secondary exposure
Dairy products contain vitamin D and other nutrients that may be beneficial for lung function, but are also high in fats that may have mixed effects on lung function. However, the overall associations of dairy intake with lung density and lung function have not been studied.
We examined the cross-sectional relations between dairy intake and CT lung density and lung function in the Multi-Ethnic Study of Atherosclerosis (MESA). Total, low-fat and high-fat dairy intakes were quantified from food frequency questionnaire responses of men and women, aged 45–84 years, free of clinical cardiovascular disease. The MESA-Lung Study assessed CT lung density from cardiac CT imaging and prebronchodilator spirometry among 3,965 MESA participants.
Total dairy intake was inversely associated with apical-basilar difference in percent emphysema and positively associated with FVC (the multivariate-adjusted mean difference between the highest and the lowest quintile of total dairy intake was −0.92 (p for trend=0.04) for apical-basilar difference in percent emphysema and 72.0 mL (p=0.01) for FVC). Greater low-fat dairy intake was associated with higher alpha (higher alpha values indicate less emphysema) and lower apical-basilar difference in percent emphysema (corresponding differences in alpha and apical-basilar difference in percent emphysema were 0.04 (p=0.02) and −0.98 (p=0.01) for low-fat dairy intake, respectively). High-fat dairy intake was not associated with lung density measures. Greater low- or high-fat dairy intake was not associated with higher FEV1, FVC and FEV1/FVC.
Higher low-fat dairy intake but not high-fat dairy intake was associated with moderately improved CT lung density.
dairy intake; lung density; emphysema; lung function; chronic obstructive pulmonary disease
Children of workers exposed to pesticides are at risk of secondary pesticide exposure. We evaluated the potential for lower acetylcholinesterase activity in children cohabiting with fresh-cut flower plantation workers, which would be expected from organophosphate and carbamate insecticide exposure. Parental home surveys were performed and acetylcholinesterase activity was measured in 277 children aged 4–9 years in the study of Secondary Exposure to Pesticides among Infants, Children and Adolescents (ESPINA). Participants lived in a rural county in Ecuador with substantial flower plantation activity.
Mean acetylcholinesterase activity was 3.14 U/ml, standard deviation (SD): 0.49. It was lower by 0.09 U/ml (95% confidence interval (CI) −0.19, −0.001) in children of flower workers (57% of participants) than non-flower workers’ children, after adjustment for gender, age, height-for-age, hemoglobin concentration, income, pesticide use within household lot, pesticide use by contiguous neighbors, examination date and residence distance to nearest flower plantation. Using a 4 level polychotomous acetylcholinesterase activity dependent variable, flower worker cohabitation (vs. not) had odds ratio 3.39 (95% CI 1.19, 9.64) for being <15th percentile compared to the highest tertile. Children cohabitating for ≥5 years (vs. never) had OR of 4.11 (95% CI: 1.17, 14.38) of AChE activity within <15th percentile compared to the highest tertile.
Cohabitation with a flower worker was related to lower acetylcholinesterase activity in children. This supports the hypothesis that the amount of take-home pesticides from flower workers suffices to decrease acetylcholinesterase activity, with lower activity associated with longer exposure.
Acetylcholinesterase; AChE; children; pesticide; organophosphate
The purpose of the study was to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM), compared to those with neither condition.
MetS and DM are associated with subclinical atherosclerosis as evidenced by coronary artery calcium (CAC).
The Multiethnic Study of Atherosclerosis included 6,814 African-American, Asian, Caucasian, and Hispanic adults aged 45–84 free of cardiovascular disease at baseline. 5,662 subjects (51% female, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac CT scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%), compared to neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years.
Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals) for incident CAC were 1.7 (1.4–2.0), 1.9 (1.4–2.4), and 1.8 (1.4–2.2) (all p<0.01) and absolute differences in mean progression (volume score) were 7.8 (4.0–11.6; p<0.01), 11.6 (2.7–20.5; p<0.05), and 22.6 (17.2–27.9; p<0.01) for those with MetS without DM, DM without MetS, and both DM and MetS, respectively. Similar findings were seen in analysis using Agatston calcium score. In addition, progression predicted CHD events in those with MetS without DM (adjusted hazard ratio 4.1, 95% CI=2.0–8.5, p<0.01) and DM (4.9 [1.3–18.4], p<0.05) among those in highest tertile of CAC increase vs. no increase).
Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared to individuals without these conditions, with progression also predicting CHD events in those with MetS and DM.
atherosclerosis; diabetes; risk factors; calcification
The cholesteryl ester transport protein (CETP) plays a key role in high-density lipoprotein (HDL) metabolism. Genetic variants that alter CETP activity and concentration may cause significant alterations in HDL-cholesterol (HDL-C) concentration; however, controversies remain about whether these genetic variants are associated with atherosclerosis. We genotyped the CETP R451Q, A373P, -629C/A, Taq1B, and -2505C/A polymorphisms in a cohort of Caucasian, Chinese, African-American, and Hispanic individuals within the Multi-Ethnic Study of Atherosclerosis. Genotypes were examined in relationship to HDL-C, CETP activity, CETP concentration, and three measures of subclinical cardiovascular disease (CVD): coronary artery calcium (CAC) measured by fast CT scanning, and carotid intimal-medial thickness (IMT) and carotid artery plaque, measured by ultrasonography. Carriers of the 451Q and 373P alleles have significantly higher CETP concentration (22.4% and 19.5%, respectively; p<0.001) and activity (13.1% and 9.4%, respectively; p<0.01) and lower HDL-C (5.6% and 6.0%, respectively; p<0.05). The minor alleles of the R451Q and A373P polymorphisms are associated with the presence of CAC, even after adjusting for CVD risk factors and HDL-C (p=0.006 and p=0.01, respectively). The R451Q polymorphism is also associated with presence of carotid artery plaque (p=0.036). Neither polymorphism is associated with common or internal carotid IMT. We confirmed that the -629A, Taq1B B2, and -2505A alleles are significantly associated with lower CETP concentration (20.8%, 25.0%, and 23.7%, respectively; p<0.001) and activity (14.8%, 19.8%, and 18.4%, respectively; p<0.001) and higher HDL-C concentration (9.7%, 11.5%, and 10.4%, respectively; p<0.01). However, we did not find any associations between these non-coding polymorphisms and subclinical CVD.
CETP; CVD; HDL; MESA
It is not known if the genes involved with endurance performance during young adulthood are also involved with changes in performance. We examined the associations of gene variants with symptom-limited exercise test duration at baseline and decrease in duration over 20 years.
Methods and Results
3,783 (1,835 Blacks 1,948 Whites) and 2,335 (1,035 Blacks 1,300 Whites) participants from CARDIA were included in the baseline and 20 year models, respectively. 217 SNPs in Blacks and 171 SNPs in Whites from 17 genes were genotyped. In Blacks, five SNPs in the ATP1A2, HIF1A, NOS3, and PPARGC1A loci tended to be associated (p<0.05) with baseline duration in a multivariate regression model. Blacks (n=99) with at least four of the most-favorable genotypes at these loci had approximately two minutes longer baseline duration than those with only two such genotypes (P<0.0001). In Whites, the HIF1A rs1957757 and PPARGC1A rs3774909 markers tended to be associated with baseline duration, but the association of a multimarker construct of the most-favorable genotypes at both SNPs with baseline duration was not statistically significant. In Whites, four SNPs in the AGT, AMPD1, ANG, and PPARGC1A loci tended to be associated with decrease in exercise duration over 20 years, and those (n=40) with all four favorable genotypes had 0.8 min less decline in duration compared to those with none or one (n=232) (P<0.0001).
In multimarker constructs, alleles at genes related to skeletal muscle Na+/K+ transport, hypoxia, and mitochondrial metabolism are associated with symptom-limited exercise test duration over time in adults.
cardiorespiratory fitness; genotype; prospective study
To examine the benefits of physical activity (PA) on diseases with a long developmental period, it is important to determine reliability of long-term PA recall.
We investigated 15-year reproducibility of PA recall. Participants were 3605 White and African-American adults in the Coronary Artery Risk Development in Young Adults study, aged 33–45 at the time of recall assessment. Categorical questions assessed PA before and during high school (HS) and overall PA level at Baseline, with the same timeframes recalled 15 years later. Moderate- and vigorous-intensity scores were calculated from reported months of participation in specific activities.
HS PA recall had higher reproducibility than overall PA recall (weighted kappa = 0.43 vs. 0.21). Correlations between 15-year recall and Baseline reports of PA were r = 0.29 for moderate-intensity scores, and r = 0.50 for vigorous-intensity. Recall of vigorous activities had higher reproducibility than moderate-intensity activities. Regardless of number of months originally reported for specific activities, most participants recalled either no activity or activity during all 12 months.
PA recall from the distant past is moderately reproducible, but poor at the individual level, among young and middle aged adults.
Lung function studies in middle-aged subjects predict cardiovascular disease (CVD) mortality. We studied if greater loss of forced vital capacity (FVC) early in life predicted incident hypertension (HTN). The sample was 3205 black and white men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) study examined between 1985-86 (CARDIA year 0, ages 18-30 years) and 2005-06 and who were not hypertensive by year 10. FVC was assessed at years 0, 2, 5, 10, and 20. Proportional hazard ratios (HR) and linear regression models predicted incident HTN at years 15 or 20 (n=508) from the change in FVC (FVC at year 10 – peak FVC, where peak FVC was estimated as the maximum across years 0, 2, 5 and 10). Covariates included demographics, center, systolic blood pressure, FVC max, smoking, physical activity, asthma and BMI. Unadjusted cumulative incident HTN was 25% in the lowest FVC loss quartile (Q1, median loss=370ml) compared to 12% cumulative incident HTN in those who achieved peak FVC at year 10 (Q4). Minimally adjusted HR for Q1 vs. Q4 was 2.21 (95% CI: 1.73-2.83) and this association remained significant in the fully adjusted model (1.37, 95% CI: 1.05-1.80). Decline in FVC from average age at peak (29.4 years) to 35 years old predicted incident hypertension between average ages 35 and 45. The findings may represent a common pathway that may link low normal FVC to cardiovascular disease morbidity and mortality.
forced vital capacity; hypertension; CARDIA; adults; cohort
To assess whether markers of acculturation (birthplace, number of U.S. generations) and socioeconomic status (SES) are associated with carotid artery plaque, internal carotid intima-media thickness (IMT), and albuminuria, in four racial/ethnic groups.
Using Multi-Ethnic Study of Atherosclerosis data (n = 6,716; age: 45-84) and race-specific binomial regression models, we computed prevalence ratios, adjusted for demographics and traditional cardiovascular risk factors.
The adjusted U.S. to foreign-born prevalence ratio (99% CI) for carotid plaque was 1.20 (0.97, 1.39) in Whites, 1.91 (0.94, 2.94) in Chinese, 1.62 (1.28, 2.06) in Blacks, and 1.23 (1.15, 1.31) in Hispanics. Greater carotid plaque prevalence was also found among Whites, Blacks, and Hispanics with more generations of US residence (p<0.001). Lower educational attainment and/or income were associated with greater carotid plaque prevalence in Whites and Blacks. Similar associations were observed with IMT. There was also some evidence of an inverse association between albuminuria and SES, in Whites and Hispanics.
Greater U.S. acculturation and lower SES were associated with a higher prevalence of carotid plaque and IMT, while little association was found with albuminuria.
The association of subclinical vascular disease and early declines in kidney function has not been well studied.
Prospective cohort study
Setting & Participants
MESA participants with eGFR ≥60 ml/min/1.73m2 with follow-up of 5 years
Pulse pressure (pulse pressure), small and large arterial elasticity (SAE, LAE), and flow mediated dilation.
kidney function decline
SAE and LAE were measured by pulse contour analysis of the radial artery. Kidney function was measured by serum creatinine- and cystatin C-based eGFR.
Among 4,853 adults, higher pulse pressure and lower SAE and LAE had independent and linear associations with faster rates of kidney function decline. Compared to persons with pulse pressure 40–50mmHg, eGFRSCysC decline was 0.29 (p=0.006), 0.56 (p<0.001), and 0.91 (p<0.001) ml/min/1.73m2/year faster among persons with pulse pressure 50–60, 60–70, and >70mmHg, respectively. Compared to the highest quartile of SAE (most elastic), eGFRSCysC decline was 0.26 (p=0.009), 0.35 (p=0.001), and 0.70 (p<0.001) ml/min/1.73m2/year faster for the second, third and fourth quartiles respectively. For LAE, compared to the highest quartile, eGFRSCysC decline was 0.28 (p=0.004), 0.58 (p<0.001), and 0.83 (p<0.001) ml/min/1.73m2/year faster for each decreasing quartile of LAE. Findings were similar with creatinine-based eGFR. In contrast, among 2,997 adults with flow-mediated dilation and kidney function measures, flow-mediated dilation was not significantly associated with kidney function decline. For every 1-SD greater flow-mediated dilation, eGFRSCysC and eGFRSCr changed by 0.05 ml/min/1.73m2/year (p=0.3) and 0.06 ml/min/1.73m2/year (p=0.04), respectively.
We had no direct measure of GFR, in common with nearly all large population based studies.
Higher pulse pressure and lower arterial elasticity, but not flow-mediated dilation, were linearly and independently associated with faster kidney function decline among persons with eGFR ≥60 ml/min/1.73m2. Future studies investigate whether treatments to lower stiffness of large and small arteries may slow the rate of kidney function loss.
kidney function; arterial elasticity; chronic kidney disease; atherosclerosis
Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45–84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA) were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV1) (P<0.001) and FEV1/forced vital capacity (FVC) ratio (P = 0.04). Albumin-to-creatinine ratio was inversely associated with FEV1 (P = 0.002) but not FEV1/FVC. Myocardial blood flow (n = 126) was associated with lower FEV1 (P = 0.02), lower FEV1/FVC (P = 0.001) and greater percentage LAA (P = 0.04). Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.
The psychometric properties of instruments used to measure self-reported experiences of discrimination in epidemiologic studies are rarely assessed, especially regarding construct validity. The authors used 2000–2001 data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study to examine differential item functioning (DIF) in 2 versions of the Experiences of Discrimination (EOD) Index, an index measuring self-reported experiences of racial/ethnic and gender discrimination. DIF may confound interpretation of subgroup differences. Large DIF was observed for 2 of 7 racial/ethnic discrimination items: White participants reported more racial/ethnic discrimination for the “at school” item, and black participants reported more racial/ethnic discrimination for the “getting housing” item. The large DIF by race/ethnicity in the index for racial/ethnic discrimination probably reflects item impact and is the result of valid group differences between blacks and whites regarding their respective experiences of discrimination. The authors also observed large DIF by race/ethnicity for 3 of 7 gender discrimination items. This is more likely to have been due to item bias. Users of the EOD Index must consider the advantages and disadvantages of DIF adjustment (omitting items, constructing separate measures, and retaining items). The EOD Index has substantial usefulness as an instrument that can assess self-reported experiences of discrimination.
African Americans; bias (epidemiology); observer variation; prejudice; psychometrics; questionnaires; reproducibility of results
Change and fluctuation in body mass index (BMI; weight (kg)/height (m)2) may be associated differently with coronary artery calcification (CAC) than with carotid artery intima-media thickness (IMT). The authors analyzed data on 2,243 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, initially aged 18–30 years, who were examined every 2–5 years over a 20-year period (1985–2006). BMI at year 0 was associated positively and linearly with CAC at year 20; however, the association of BMI with year 20 CAC became progressively U-shaped in subsequent examinations (years 10, 15, and 20). To understand the deepening U shape, the authors modeled year 20 BMI and its history using 3 indices: year 0 BMI, linear slope of BMI during 20 years, and BMI fluctuation during 20 years. In models including these 3 terms, year 0 BMI was associated positively with CAC, as was BMI fluctuation. However, adjusted odds ratios across quintiles of BMI slope (vs. the lowest quintile) were 0.7, 0.4, 0.5, and 0.4 (Ptrend < 0.01), suggesting higher risk of CAC with weight loss, plateauing after moderate weight gain. In contrast, IMT was associated positively with BMI at all examinations and with 20-year BMI slope and was unassociated with BMI fluctuation. Surprisingly, CAC risk was higher with BMI loss and lower with BMI gain, whereas associations with IMT were as expected.
body mass index; body weight changes; carotid artery, common; coronary vessels; tunica intima; tunica media