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1.  Rural and urban differences in metabolic profiles in a Cameroonian population 
The difference between modern lifestyle in urban areas and the traditional way of life in rural areas may affect the population's health in developing countries proportionally. In this study, we sought to describe and compare the metabolic (fasting blood sugar and lipid profile) profile in an urban and rural sample of a Cameroonian population, and study the association to anthropometric risk factors of obesity.
332 urban and 120 rural men and women originating from the Sanaga Maritime Department and living in the Littoral Region in Cameroon voluntarily participated in this study. In all participants, measurement of height, weight, waist circumference, hip circumference, blood pressure systolic (SBP) and blood pressure diastolic (DBP), resting heart rate (RHR), blood glucose and lipids was carried out using standard methods. Total body fat (BF%) was measured using bio-impedancemetry. Body mass index (BMI) and waist to hip ratio (WHR) were calculated. Low Density Lipoprotein-cholesterol (LDL-c) concentrations were calculated using the Friedwald formula. World Health Organization criteria were used to define high and low levels of blood pressure, metabolic and anthropometric factors.
The highest blood pressure values were found in rural men. Concerning resting heart rate, only the youngest women's age group showed a significant difference between urban and rural areas (79 ± 14 bpm vs 88 ± 12 bpm, p = 0.04) respectively. As opposed to the general tendency in our population, blood glucose was higher in rural men and women compared to their urban counterparts in the older age group (6.00 ± 2.56 mmol/L vs 5.72 ± 2.72 mmol/L, p = 0.030; 5.77 ± 3.72 vs 5.08 ± 0.60, p = 0,887 respectively). Triglycerides (TG) were significantly higher in urban than rural men (1.23 ± 0.39 mmol/L vs 1.17 ± 0.64 mmol/L, p = 0.017). High Density Lipoprotein-cholesterol (HDL-c) levels were higher in rural compared to urban men (2.60 ± 0.10 35mmol/L vs 1.97 ± 1.14 mmol/L, p<0.001 respectively). However, total Cholesterol (TC) and LDL-c were significantly higher in urban than in rural men (p<0.001 and p = 0.005) and women (p<0.001 respectively. Diabetes’ rate in this population was 6.6%. This rate was higher in the rural (8.3%) than in the urban area (6.0%). Age and RHR were significantly higher in diabetic women than in non-diabetics (p = 0.007; p = 0.032 respectively). In a multiple regression, age was an independent predictor of SBP, DBP and RHR in the entire population. Age predicted blood glucose in rural women only. BMI, WC and BF% were independent predictors of RHR in rural population, especially in men. WC and BF% predicted DBP in rural men only. Anthropometric parameters did not predict the lipid profile.
Lipid profile was less atherogenic in rural than in urban area. The rural population was older than the urban one. Blood pressure and blood glucose were positively associated to age in men and women respectively; this could explain the higher prevalence of diabetes in rural than in urban area. The association of these metabolic variables to obesity indices is more frequent and important in urban than in rural area.
PMCID: PMC3282926  PMID: 22187583
Adults; anthropometry; lipid profile; blood glucose; blood pressure; diabetes; urban; rural; Cameroon
2.  Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the INternational VErapamil-SR/trandolapril STudy (INVEST) 
European heart journal  2008;29(10):1327-1334.
To determine the relationship between resting heart rate (RHR) and adverse outcomes in coronary artery disease (CAD) patients treated for hypertension with different RHR-lowering strategies.
Methods and results
Time to adverse outcomes (death, non-fatal myocardial infarction, or non-fatal-stroke) and predictive values of base-line and follow-up RHR were assessed in INternational VErapamil-SR/trandolapril STudy (INVEST) patients randomized to either a verapamil-SR (Ve) or atenolol (At)-based strategy. Higher baseline and follow-up RHR were associated with increased adverse outcome risks, with a linear relationship for baseline RHR and J-shaped relationship for follow-up RHR. Although follow-up RHR was independently associated with adverse outcomes, it added less excess risk than baseline conditions such as heart failure and diabetes. The At strategy reduced RHR more than Ve (at 24 months, 69.2 vs. 72.8 beats/min; P < 0.001), yet adverse outcomes were similar [Ve 9.67% (rate 35/1000 patient-years) vs. At 9.88% (rate 36/1000 patient-years, confidence interval 0.90–1.06, P = 0.62)]. For the same RHR, men had a higher risk than women.
Among CAD patients with hypertension, RHR predicts adverse outcomes, and on-treatment RHR is more predictive than baseline RHR. A Ve strategy is less effective than an At strategy for lowering RHR but has a similar effect on adverse outcomes.
PMCID: PMC2805436  PMID: 18375982
Coronary artery disease; Atenolol; Resting heart rate; Adverse outcomes; INVEST; Verapamil-SR
3.  A Prospective Population Study of Resting Heart Rate and Peak Oxygen Uptake (the HUNT Study, Norway) 
PLoS ONE  2012;7(9):e45021.
We assessed the prospective association of resting heart rate (RHR) at baseline with peak oxygen uptake (VO2peak) 23 years later, and evaluated whether physical activity (PA) could modify this association.
Both RHR and VO2peak are strong and independent predictors of cardiovascular morbidity and mortality. However, the association of RHR with VO2peak and modifying effect of PA have not been prospectively assessed in population studies.
In 807 men and 810 women free from cardiovascular disease both at baseline (1984–86) and follow-up 23 years later, RHR was recorded at both occasions, and VO2peak was measured by ergospirometry at follow-up. We used Generalized Linear Models to assess the association of baseline RHR with VO2peak, and to study combined effects of RHR and self-reported PA on later VO2peak.
There was an inverse association of RHR at baseline with VO2peak (p<0.01). Men and women with baseline RHR greater than 80 bpm had 4.6 mL·kg−1·min−1 (95% confidence interval [CI], 2.8 to 6.3) and 1.4 mL·kg−1·min−1 (95% CI, −0.4 to 3.1) lower VO2peak at follow-up compared with men and women with RHR below 60 bpm at baseline. We found a linear association of change in RHR with VO2peak (p = 0.03), suggesting that a decrease in RHR over time is likely to be beneficial for cardiovascular fitness. Participants with low RHR and high PA at baseline had higher VO2peak than inactive people with relatively high RHR. However, among participants with relatively high RHR and high PA at baseline, VO2peak was similar to inactive people with relatively low RHR.
RHR is an important predictor of VO2peak, and serial assessments of RHR may provide useful and inexpensive information on cardiovascular fitness. The results suggest that high levels of PA may compensate for the lower VO2peak associated with a high RHR.
PMCID: PMC3445602  PMID: 23028740
4.  The Product of Resting Heart Rate Times Blood Pressure Is Associated with High Brachial-Ankle Pulse Wave Velocity 
PLoS ONE  2014;9(9):e107852.
To investigate potential associations between resting heart rate, blood pressure and the product of both, and the brachial-ankle pulse wave velocity (baPWV) as a maker of arterial stiffness.
The community-based “Asymptomatic Polyvascular Abnormalities in Community (APAC) Study” examined asymptomatic polyvascular abnormalities in a general Chinese population and included participants with an age of 40+ years without history of stroke and coronary heart disease. Arterial stiffness was defined as baPWV≥1400 cm/s. We measured and calculated the product of resting heart rate and systolic blood pressure (RHR-SBP) and the product of resting heart rate and mean arterial pressure (RHR-MAP).
The study included 5153 participants with a mean age of 55.1±11.8 years. Mean baPWV was 1586±400 cm/s. Significant (P<0.0001) linear relationships were found between higher baPWV and higher resting heart rate or higher arterial blood pressure, with the highest baPWV observed in individuals from the highest quartiles of resting heart rate and blood pressure. After adjusting for confounding parameters such as age, sex, educational level, body mass index, fasting blood concentrations of glucose, blood lipids and high-sensitive C-reactive protein, smoking status and alcohol consumption, prevalence of arterial stiffness increased significantly (P<0.0001) with increasing RHR-SBP quartile (Odds Ratio (OR): 2.72;95%Confidence interval (CI):1.46,5.08) and increasing RHR-MAP (OR:2.10;95%CI:1.18,3.72). Similar results were obtained in multivariate linear regression analyses with baPWV as continuous variable.
Higher baPWV as a marker of arterial stiffness was associated with a higher product of RHR-SBP and RHR-MAP in multivariate analysis. In addition to other vascular risk factors, higher resting heart rate in combination with higher blood pressure are risk factors for arterial stiffness.
PMCID: PMC4166598  PMID: 25225895
5.  Resting Heart Rate and Coronary Artery Calcium in Postmenopausal Women 
Journal of Women's Health  2011;20(5):661-669.
To test the hypothesis of a significant association between resting heart rate (RHR) and coronary artery calcium (CAC).
This is a cross-sectional study of a subset of women enrolled in the estrogen-alone clinical trial of the Women's Health Initiative (WHI). We used a longitudinal study that enrolled 998 postmenopausal women with a history of hysterectomy between the ages of 50 and 59 at enrollment at 40 different clinical centers. RHR was measured at enrollment and throughout the study, and CAC was determined approximately 7 years after the baseline clinic visit.
The mean (standard deviation [SD]) age was 55 (2.8) years. With adjustment for age and ethnicity, a 10-unit increment in RHR was significantly associated with CAC (SD 1.18, 95% confidence interval [CI] 1.01-1.38), but this was no longer significant after adjustment for body mass index (BMI), income, education, dyslipidemia, diabetes, smoking, and hypertension (SD 1.06, 95% CI 0.90-1.25). In a fully adjusted multivariable model, however, there was a significant interaction (p=0.03) between baseline RHR and systolic blood pressure (SBP) for the presence of any CAC. Compared to women with an RHR < 80 beats per minute (BPM) and an SBP < 140 mm Hg, those who had an RHR ≥ 80 BPM and an SBP ≥ 140 mm Hg had 2.66-fold higher odds (1.08-6.57) for the presence of any CAC.
Compared to those with normal BP and RHR, postmenopausal, hysterectomized women with an elevated SBP and RHR have a significantly higher odds for the presence of calcified coronary artery disease.
PMCID: PMC3096501  PMID: 21438696
6.  The Effect of Intensive Diabetes Treatment on Resting Heart Rate in Type 1 Diabetes 
Diabetes care  2007;30(8):2107-2112.
Cardiovascular disease is a major cause of morbidity and mortality in individuals with type 1 diabetes. Resting heart rate (RHR) is a risk factor for cardiovascular disease in the general population, and case-control studies have reported a higher RHR in individuals with type 1 diabetes. In individuals with type 1 diabetes, there is a positive correlation between A1C and RHR; however, no prospective studies have examined whether a causal relationship exists between A1C and RHR. We hypothesized that intensive diabetes treatment aimed to achieve normal A1C levels has an effect on RHR in individuals with type 1 diabetes.
A total of 1,441 individuals with type 1 diabetes who participated in the Diabetes Control and Complications Trial (DCCT) had their RHR measured biennially by an electrocardiogram during the DCCT and annually for 10 years during the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study.
During the DCCT, intensive treatment was associated with lower mean RHR than conventional treatment, both in adolescents (69.0 vs. 72.0 bpm [95% CI 62.8–75.7 and 65.7–78.9, respectively], P = 0.013) and adults (66.8 vs. 68.2 [65.3– 68.4 and 66.6–69.8, respectively], P = 0.0014). During follow-up in the EDIC, the difference in RHR between the treatment groups persisted for at least 10 years (P < 0.0001).
Compared with conventional therapy, intensive diabetes management is associated with lower RHR in type 1 diabetes. The lower RHR with intensive therapy may explain, in part, its effect in reducing cardiovascular disease, recently demonstrated in type 1 diabetes.
PMCID: PMC2654598  PMID: 17468351
7.  Combined Effects of Depressive Symptoms and Resting Heart Rate on Mortality: The Whitehall II Prospective Cohort Study 
The Journal of clinical psychiatry  2010;72(9):1199-1206.
To examine the combined effects of depressive symptoms and resting heart rate (RHR) on mortality.
Data come from 5936 participants, aged 61 ± 6 years, from the Whitehall II study. Depressive symptoms were assessed in 2002–2004 using the center-for-epidemiologic-studies-depression-scale (score ≥ 16). RHR was measured at the same study phase via electrocardiogram. Participants were assigned to 1 of 6 risk-factor-groups based on depression status (yes/no) and RHR categories (<60, 60 – 80, >80 bpm). Mean follow-up for mortality was 5.6 years.
In mutually adjusted Cox regression models, depression (hazard ratio = 1.93 p<0.001) and RHR>80 bpm (hazard ratio = 1.67, p<0.001) were independent predictors of mortality. After adjustment for potential confounding and mediating variables, participants with both depression and high RHR had a 3.0-fold higher (p<0.001) risk of death compared to depression-free participants with RHR ranging from 60 to 80 bpm. This risk is particularly marked in participants with prevalent CHD.
This study provides evidence that the coexistence of depressive symptoms and elevated RHR is associated with substantially increased risk of death compared to those without these two factors. This finding raises the possibility that treatments that improve both depression and RHR might improve survival.
PMCID: PMC3226937  PMID: 21208592
depression; resting heart rate and mortality
8.  Combined effects of depressive symptoms and resting heart rate on mortality: the Whitehall II prospective cohort study 
The Journal of Clinical Psychiatry  2010;72(9):1199-1206.
To examine the combined effects of depressive symptoms and resting heart rate (RHR) on mortality.
Data come from 5936 participants, aged 61 ±6 years, from the Whitehall II study. Depressive symptoms were assessed in 2002–2004 using the center-for-epidemiologic-studies-depression-scale (score ≥16). RHR was measured at the same study phase via electrocardiogram. Participants were assigned to 1 of 6 risk-factor-groups based on depression status (yes/no) and RHR categories (<60, 60–80, >80 bpm). Mean follow-up for mortality was 5.6 years.
In mutually adjusted Cox regression models, depression (hazard ratio = 1.93 p<0.001) and RHR>80 bpm (hazard ratio = 1.67, p<0.001) were independent predictors of mortality. After adjustment for potential confounding and mediating variables, participants with both depression and high RHR had a 3.0-fold higher (p<0.001) risk of death compared to depression-free participants with RHR ranging from 60 to 80 bpm. This risk is particularly marked in participants with prevalent CHD.
This study provides evidence that the coexistence of depressive symptoms and elevated RHR is associated with substantially increased risk of death compared to those without these two factors. This finding raises the possibility that treatments that improve both depression and RHR might improve survival.
PMCID: PMC3226937  PMID: 21208592
depression; resting heart rate and mortality
9.  The Inverse Association between Cardiorespiratory Fitness and C-Reactive Protein Is Mediated by Autonomic Function: A Possible Role of the Cholinergic Antiinflammatory Pathway 
Molecular Medicine  2009;15(9-10):291-296.
Although studies have shown an inverse association between cardiorespiratory fitness (CRF) and C-reactive protein (CRP) levels, the underlying mechanisms are not fully understood. There is emerging evidence that autonomic nervous system function is related to CRP levels. Because high CRF is related to improved autonomic function, we hypothesized that the association between high CRF and low CRP levels would be affected by autonomic nervous system function. Cross-sectional analyses were conducted on 2,456 asymptomatic men who participated in a medical screening program. Fasting blood samples for cardiovascular disease risk factors were analyzed, and CRF was measured by maximal exercise treadmill test with expired gas analysis. We used an index of cardiac autonomic imbalance defined as the ratio of resting heart rate to 1 min of heart rate recovery after exercise (RHR/HRR). CRF was significantly correlated with CRP (r = −0.16, P < 0.05), and RHR/HRR (r = −0.48, P < 0.05), while RHR/HRR was significantly correlated with CRP (r = 0.25, P < 0.05). In multivariable linear regression models that adjusted for age, body mass index, smoking, disease status, medications, lipid profiles, glucose, and systolic blood pressure, CRF was inversely associated with CRP (β = −0.09, P < 0.05). However, this relationship was no longer significant after adjusting for RHR/HRR in a multivariable linear regression model (β = −0.03, P = 0.29). These results suggest that autonomic nervous system function significantly affects the relationship between CRF and inflammation in middle-aged men. Thus, physical activity or exercise training may favorably affect the cholinergic antiinflammatory pathway, but additional research is needed to confirm this finding.
PMCID: PMC2710293  PMID: 19603105
10.  Elevated resting heart rate, physical fitness and all-cause mortality: a 16-year follow-up in the Copenhagen Male Study 
Heart  2013;99(12):882-887.
To examine whether elevated resting heart rate (RHR) is an independent risk factor for mortality or a mere marker of physical fitness (VO2Max).
This was a prospective cohort study: the Copenhagen Male Study, a longitudinal study of healthy middle-aged employed men. Subjects with sinus rhythm and without known cardiovascular disease or diabetes were included. RHR was assessed from a resting ECG at study visit in 1985–1986. VO2Max was determined by the Åstrand bicycle ergometer test in 1970–1971. Subjects were classified into categories according to level of RHR. Associations with mortality were studied in multivariate Cox models adjusted for physical fitness, leisure-time physical activity and conventional cardiovascular risk factors.
2798 subjects were followed for 16 years. 1082 deaths occurred. RHR was inversely related to physical fitness (p<0.001). Overall, increasing RHR was highly associated with mortality in a graded manner after adjusting for physical fitness, leisure-time physical activity and other cardiovascular risk factors. Compared to men with RHR ≤50, those with RHR >90 had an HR (95% CI) of 3.06 (1.97 to 4.75). With RHR as a continuous variable, risk of mortality increased with 16% (10–22) per 10 beats per minute (bpm). There was a borderline interaction with smoking (p=0.07); risk per 10 bpm increase in RHR was 20% (12–27) in smokers, and 14% (4–24) in non-smokers.
Elevated RHR is a risk factor for mortality independent of physical fitness, leisure-time physical activity and other major cardiovascular risk factors.
PMCID: PMC3664385  PMID: 23595657
Coronary Physiology; Cardiac Function
11.  Factors associated with relapse into drug use among male and female attendees of a three-month drug detoxification–rehabilitation programme in Dhaka, Bangladesh: a prospective cohort study 
To determine relapse rates and associated factors among people who use drugs (PWUDs) attending abstinence-oriented drug treatment clinics in Dhaka, Bangladesh.
A cohort of male and female PWUDs admitted to the 3-month drug detoxification-rehabilitation treatment programmes of three non-governmental organisation-run drug treatment clinics in Dhaka, Bangladesh were interviewed on admission and over the following 5 months, which included the first 2 months after discharge. The study subjects comprised 150 male and 110 female PWUDs who had been taking opiates/opioids, cannabis or other drugs (including sedatives) before admission, had provided informed consent and were aged ≥16 years. Interviews were conducted using semi-structured questionnaires at four time points; on admission, at discharge and at 1 and 2 months after discharge. Relapse rates were assessed by the Kaplan–Meier method. Factors associated with relapse on enrolment and after discharge were determined using the Cox proportional hazards regression model.
A greater proportion of female than male subjects relapsed over the study period (71.9% versus 54.5%, p < 0.01). For men, baseline factors associated with relapse were living with other PWUDs (relative hazard ratio [RHR] = 2.27), living alone (RHR = 2.35) and not having sex with non-commercial partners (RHR = 2.27); whereas for women these were previous history of drug treatment (RHR = 1.94), unstable housing (RHR = 2.44), higher earnings (RHR = 1.89), preferring to smoke heroin (RHR = 3.62) and injecting buprenorphine/pethidine (RHR = 3.00). After discharge, relapse for men was associated with unstable housing (RHR = 2.78), living alone (RHR = 3.69), higher earnings (RHR = 2.48) and buying sex from sex workers (RHR = 2.29). Women’ relapses were associated with not having children to support (RHR = 3.24) and selling sex (RHR = 2.56).
The relapse rate was higher for female PWUDs. For both male and female subjects the findings highlight the importance of stable living conditions. Additionally, female PWUDs need gender-sensitive services and active efforts to refer them for opioid substitution therapy, which should not be restricted only to people who inject drugs.
PMCID: PMC3846454  PMID: 24004685
Relapse; Gender; Drug detoxification-rehabilitation; People who use drugs; Bangladesh
12.  Resting heart rate in patients with ischemic heart disease in Saudi Arabia and Egypt 
To assess the level of resting heart rate (RHR) in an outpatient population presenting with stable coronary artery disease (CAD) as well as to measure its association with current therapeutic management strategies for cardiovascular events.
Materials and methods
A multi-center cross-sectional survey was carried out in Saudi Arabia and Egypt over a three month period (between January 2007 and April 2007). 2049 patients with CAD without clinical heart failure (HF) were included in this study through “cluster sampling”. RHR was measured by manual palpitation.
Mean age of CAD patients was 56.7 ± 10.4 and the mean RHR was 78.9 ± 13.9 b/m. 1686 patients (83.1%) were on β-blockers for whom the RHR was 78.5 ± 14.0 b/m (95.5% had RHR ⩾ 60 b/m, which is higher than recommended by the guidelines). 1094 (73.5%) of patients on β-blockers were on a lower dose, probably to avoid the complications associated with such a class. Among those not on β-blockers (16.9%), RHR was 80.9 ± 13.0 b/m.
Moreover, 98 patients (4.8%) were on calcium channel blocker (diltiazem or verapamil) but not on β-blockers, for whom the RHR was 80.9 ± 12.0 b/m. Finally, 163 patients (8.0%) were on both β-blockers and the calcium channel blocker, and their RHR was 79.0 ± 14.4 b/m.
Optimal target RHR has not been achieved in a significant number of screened patients. Achievements of such targets are known to decrease mortality and to improve survival.
PMCID: PMC3727557  PMID: 23960653
RHR, resting heart rate; CAD, coronary artery disease; NYHA, New York Heart Association Classification; HF, heart failure; Resting heart rate; Saudi Arabia; Egypt; Outcome
13.  Resting Heart Rate and Risk of Cardiovascular Diseases and All-Cause Death: The Kailuan Study 
PLoS ONE  2014;9(10):e110985.
Resting heart rate (RHR) predicts both cardiovascular and noncardiovascular death in different populations. However, the results of the association between RHR and cardiovascular diseases (CVDs) are inconsistent, especially for each subtype of CVDs.
The aim of this study was to prospectively explore the relationship between RHR and CVDs including myocardial infarction (MI), ischemic stroke, and hemorrhagic stroke and all-cause death in a general population.
The Kailuan study is a prospective longitudinal cohort study on cardiovascular risk factors and cardiovascular or cerebrovascular events. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling.
We analyzed 92,562 participants (18–98 years old) in the Kailuan Study. CVDs were developed in 1,903 people during follow-ups. In multivariate analysis with adjustment for major traditional cardiovascular risk factors, HRs of the highest quintile group compared with the lowest quintile group of RHR for all-cause CVDs, MI, any stroke, ischemic stroke, hemorrhagic stroke, and all-cause death were 1.03 (95% CI, 0.98–1.07), 1.10 (95% CI, 1.01–1.20), 1.01 (95% CI, 0.97–1.06), 1.02 (95% CI, 0.96–1.07), 1.01 (95% CI, 0.92–1.11) and 1.18, (95% CI, 1.13–1.23), respectively.
The elevated RHR was independently associated with the increased risk for MI and all-cause death, but not for all-cause CVDs, any stroke, ischemic stroke, nor hemorrhagic stroke. This indicates that the elevated RHR might be a risk marker for MI and all-cause death in general populations.
PMCID: PMC4208799  PMID: 25343354
14.  Exercise Dose, Exercise Adherence, and Associated Health Outcomes in the TIGER Study 
Medicine and science in sports and exercise  2014;46(1):10.1249/MSS.0b013e3182a038b9.
To effectively evaluate activity-based interventions for weight management and disease risk reduction, objective and accurate measures of exercise dose are needed. This study examined cumulative exercise exposure defined by heart rate-based intensity, duration, and frequency as a measure of compliance with a prescribed exercise program and a predictor of health outcomes.
1,150 adults (21.3 ± 2.7 yrs) completed a 15-week exercise protocol consisting of 30 min/day, three days/wk at 65–85% maximum heart rate reserve (HRR). Computerized HR monitor data were recorded at every exercise session (33,473 valid sessions). To quantify total exercise dose, duration for each session was adjusted for average exercise intensity (%HRR) to create a measure of intensity-minutes for each workout, which were summed over all exercise sessions to formulate a heart rate physical activity score (HRPAS). Regression analysis was used to examine the relationship between HRPAS and physiological responses to exercise training. Compliance with the exercise protocol based on achievement of the minimum prescribed HRPAS was compared to adherence defined by attendance.
Using HRPAS, 868 participants were empirically defined as compliant, and 282 were non-compliant. HRPAS-based and attendance-based classifications of compliance and adherence differed for approximately 9% of participants. Higher HRPAS was associated with significant positive changes in body mass (p<0.001), BMI (p<0.001), waist and hip circumferences (p<0.001), percent body fat (%Fat, p<0.001), systolic blood pressure (p<0.011), resting heart rate (RHR, p<0.003), fasting glucose (p<0.001), and total cholesterol (p<.02). Attendance-based adherence was associated with body mass, hip circumference, %Fat, RHR, and cholesterol (p<0.05).
The HRPAS is a quantifiable measure of exercise dose associated with improvement in health indicators beyond that observed when adherence is defined as session attendance.
PMCID: PMC3867583  PMID: 23793231
heart rate; physical activity; monitoring; dropout; attrition; compliance
15.  Protective Role of Resting Heart Rate on All-Cause and Cardiovascular Disease Mortality 
Mayo Clinic proceedings  2013;88(12):1420-1426.
To study the protective role of lower resting heart rate (RHR) on cardiovascular disease (CVD) and all-cause mortality.
Patients and Methods
Participants (n=51,936) who received a baseline medical examination between January 1, 1974 and December 31, 2002 were recruited from the Cooper Clinic, Dallas, Texas. They completed a medical questionnaire and underwent clinical evaluation. Participants with CVD or cancer, those who did not achieve at least 85% of their age-predicted maximal heart rate or who had <1 year of mortality follow-up were excluded from the study. SAS was used for statistical analysis. Relative risks and 95% confidence intervals of all-cause and CVD mortality across RHR categories were estimated using Cox proportional hazard models.
Highest cardiorespiratory fitness (CRF) with lower mortality was found in individuals with a RHR <60 bpm. Similarly, participants with a higher RHR, >80 bpm, were at greater risk for both CVD and all-cause mortality when compared with RHR <60 bpm. This analysis was followed by the stratification of the data by hypertension, where hypertensive individuals with high RHRs (≥80 bpm) were found at greater risk for CVD and all-cause mortality when compared to those with hypertension and lower RHRs (<60 bpm). Additionally unfit individuals with high RHR had the greatest risk for CVD and all-cause mortality. Interestingly, the unfit with low RHR group had a similar risk for both CVD and all-cause mortality as the fit with high RHR group.
Lower levels of CRF and higher RHR are linked with greater CVD and all-cause mortality1.
PMCID: PMC3908776  PMID: 24290115
16.  Prognostic Value of Resting Heart Rate on Cardiovascular and Renal Outcomes in Type 2 Diabetic Patients 
Diabetes Care  2012;35(10):2069-2075.
Epidemiological studies and randomized clinical trials have demonstrated in various populations that resting heart rate (RHR) was an independent predictor of cardiovascular (CV) risk and all-cause mortality. However, few data specifically evaluated the relationship between RHR and long-term CV and renal complications in a large population of type 2 diabetic (T2D) patients.
We performed a single-center, prospective analysis in 1,088 T2D patients. RHR was determined at baseline by electrocardiogram. The primary outcome was a composite criterion of CV and renal morbi-mortality (CV death, nonfatal myocardial infarction and/or stroke, hospitalization for heart failure, renal replacement therapy), which was adjusted for death from non-CV cause as a competing event. The secondary outcome was a renal composite criterion (renal replacement therapy or doubling of baseline serum creatinine) adjusted for all-cause death as a competing event.
During median follow-up of 4.2 years, 253 patients (23%) and 62 patients (6%) experienced the primary and secondary outcomes, respectively. In the subgroup of patients with CV disease history at baseline (n = 336), RHR was found to be associated with the incidence of primary outcome (P = 0.0002) but also with renal risk alone, adjusted for all-cause death as a competing event (secondary outcome; P < 0.0001). In patients without history of CV disease, no relation was found between RHR and the incidence of CV and/or renal events.
In the real-life setting, RHR constitutes an easy and less time-consuming factor that would permit identification of CV disease diabetic patients with an increased risk for long-term CV and renal complications.
PMCID: PMC3447829  PMID: 22815300
17.  Prognostic significance of heart rate turbulence parameters in patients with chronic heart failure 
This study is aimed to evaluate the clinical significance of heart rate turbulence (HRT) parameters in predicting the prognosis in patients with chronic heart failure (CHF).
From June 2011 to December 2012, a total of 104 CHF patients and 30 healthy controls were enrolled in this study. We obtained a 24-hour Holter ECG recording to assess the HRT parameters, included turbulence onset (TO), turbulence slope (TS), standard deviation of N-N intervals (SDNN), and resting heart rate (RHR). The relationships between HRT parameters and the prognosis of CHF patients were determined.
The assessment follow-up period lasted until January 31, 2013. The overall mortality of CHF patients was 9.6% (10/104). Our results revealed that CHF patients had higher levels of TO than those of healthy subjects, but the TS levels of CHF patients were lower than that of the control group. CHF patients with NYHA grade IV had higher HRT1/2 rate than those with NYHA grade II/III. There were statistical differences in TS, LVEF, SDNN and RHR between the non-deteriorating group and the non-survivor group. Significant differences in TS among the three groups were also found. Furthermore, CHF patients in the non-survivor group had lower levels of TS than those in the deteriorating group. Correlation analyses indicated that TO negatively correlate with SDNN, while TS positively correlated with SDNN and left ventricular ejection fraction (LVEF). We also observed negative correlations between TS and left ventricular end-diastolic cavity dimension (LVEDD), RHR, homocysteine (Hcy) and C-reactive protein (CRP). Multivariate Cox regression analysis further confirmed that LVEF (≤30%), HRT2, SDNN and RHR were independent risk factors which can indicate poor prognosis in CHF patients.
Our findings indicate that HRT may have good clinical predictive value in patients with CHF. Thus, quantifying HRT parameters could be a useful tool for predicting mortality in CHF patients.
PMCID: PMC3996196  PMID: 24725657
Heart rate turbulence; Chronic heart failure; Prognosis
18.  High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study 
BMC Medicine  2013;11:44.
The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents.
This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined.
ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides ≥90th percentile (P <0.02) and impaired fasting glucose or glucose tolerance (P <0.001). Higher cortisol levels were found in subjects with blood pressure ≥95th percentile and LDL-cholesterol ≥90th percentile. Overall, the highest tertiles of ACTH (>5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population.
In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia, while high cortisol is associated with hypertension and high LDL-cholesterol. These specific relationships suggest complex mechanisms through which the HPA axis may contribute to metabolic impairments in obesity, and merit further investigations.
PMCID: PMC3621818  PMID: 23425018
ACTH; cardiovascular risk; cortisol; glucose; hypertension; lipids; obesity; pediatric
19.  Physical activity and sedentary behaviour in relation to cardiometabolic risk in children: cross-sectional findings from the Physical Activity and Nutrition in Children (PANIC) Study 
Lower levels of physical activity (PA) and sedentary behaviour (SB) have been associated with increased cardiometabolic risk among children. However, little is known about the independent and combined associations of PA and SB as well as different types of these behaviours with cardiometabolic risk in children. We therefore investigated these relationships among children.
The subjects were a population sample of 468 children 6–8 years of age. PA and SB were assessed by a questionnaire administered by parents and validated by a monitor combining heart rate and accelerometry measurements. We assessed body fat percentage, waist circumference, blood glucose, serum insulin, plasma lipids and lipoproteins and blood pressure and calculated a cardiometabolic risk score using population-specific Z-scores and a formula waist circumference + insulin + glucose + triglycerides - HDL cholesterol + mean of systolic and diastolic blood pressure. We analysed data using multivariate linear regression models.
Total PA was inversely associated with the cardiometabolic risk score (β = -0.135, p = 0.004), body fat percentage (β = -0.155, p < 0.001), insulin (β = -0.099, p = 0.034), triglycerides (β = -0.166, p < 0.001), VLDL triglycerides (β = -0.230, p < 0.001), VLDL cholesterol (β = -0.168, p = 0.001), LDL cholesterol (β = -0.094, p = 0.046) and HDL triglycerides (β = -0.149, p = 0.004) and directly related to HDL cholesterol (β = 0.144, p = 0.002) adjusted for age and gender. Unstructured PA was inversely associated with the cardiometabolic risk score (β = -0.123, p = 0.010), body fat percentage (β = -0.099, p = 0.027), insulin (β = -0.108, p = 0.021), triglycerides (β = -0.144, p = 0.002), VLDL triglycerides (β = -0.233, p < 0.001) and VLDL cholesterol (β = -0.199, p < 0.001) and directly related to HDL cholesterol (β = 0.126, p = 0.008). Watching TV and videos was directly related to the cardiometabolic risk score (β = 0.135, p = 0.003), body fat percentage (β = 0.090, p = 0.039), waist circumference (β = 0.097, p = 0.033) and systolic blood pressure (β = 0.096, p = 0.039). Resting was directly associated with the cardiometabolic risk score (β = 0.092, p = 0.049), triglycerides (β = 0.131, p = 0.005), VLDL triglycerides (β = 0.134, p = 0.009), VLDL cholesterol (β = 0.147, p = 0.004) and LDL cholesterol (β = 0.105, p = 0.023). Other types of PA and SB had less consistent associations with cardiometabolic risk factors.
The results of our study emphasise increasing total and unstructured PA and decreasing watching TV and videos and other sedentary behaviours to reduce cardiometabolic risk among children.
Trial registration Identifier: NCT01803776.
PMCID: PMC4008488  PMID: 24766669
Child; Metabolic diseases/metabolism; Motor activity/physiology; Risk factors; Sedentary lifestyle
20.  Resting heart rate: its correlations and potential for screening metabolic dysfunctions in adolescents 
BMC Pediatrics  2013;13:48.
In pediatric populations, the use of resting heart rate as a health index remains unclear, mainly in epidemiological settings. The aims of this study were to analyze the impact of resting heart rate on screening dyslipidemia and high blood glucose and also to identify its significance in pediatric populations.
The sample was composed of 971 randomly selected adolescents aged 11 to 17 years (410 boys and 561 girls). Resting heart rate was measured with oscillometric devices using two types of cuffs according to the arm circumference. Biochemical parameters triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and glucose were measured. Body fatness, sleep, smoking, alcohol consumption and cardiorespiratory fitness were analyzed.
Resting heart rate was positively related to higher sleep quality (β = 0.005, p = 0.039) and negatively related to cardiorespiratory fitness (β = −0.207, p = 0.001). The receiver operating characteristic curve indicated significant potential for resting heart rate in the screening of adolescents at increased values of fasting glucose (area under curve = 0.611 ± 0.039 [0.534 – 0.688]) and triglycerides (area under curve = 0.618 ± 0.044 [0.531 – 0.705]).
High resting heart rate constitutes a significant and independent risk related to dyslipidemia and high blood glucose in pediatric populations. Sleep and cardiorespiratory fitness are two important determinants of the resting heart rate.
PMCID: PMC3621598  PMID: 23560541
Heart rate; Adipose tissue; Sleep; Physical fitness; Lipid; Glucose; Adolescent
21.  Social Information Processing and Cardiac Predictors of Adolescent Antisocial Behavior 
Journal of Abnormal Psychology  2008;117(2):253-267.
The relations among social information processing (SIP), cardiac activity, and antisocial behavior were investigated in adolescents over a 3-year period (from ages 16 to 18) in a community sample of 585 (48% female, 17% African American) participants. Antisocial behavior was assessed in all 3 years. Cardiac and SIP measures were collected between the first and second behavioral assessments. Cardiac measures assessed resting heart rate (RHR) and heart rate reactivity (HRR) as participants imagined themselves being victimized in hypothetical provocation situations Portrayed via video vignettes. The findings were moderated by gender and supported a multiprocess model in which antisocial behavior is a function of trait-like low RHR (for male individuals only) and deviant SIP. In addition, deviant SIP mediated the effects of elevated HRR reactivity and elevated RHR on antisocial behavior (for male and female participants).
PMCID: PMC3391970  PMID: 18489202
antisocial behavior; heart rate; social information processing; adolescents
22.  The association of intensity and overall level of physical activity energy expenditure with a marker of insulin resistance 
Diabetologia  2008;51(8):1399-1407.
Physical activity is important in preventing insulin resistance, but it is unclear which dimension of activity confers this benefit. We examined the association of overall level and intensity of physical activity with fasting insulin level, a marker of insulin resistance.
This was a cross-sectional analysis of the Medical Research Council Ely population-based cohort study (2000–2002). Physical activity energy expenditure (PAEE) in kJ kg−1 min−1 was measured by heart rate monitoring with individual calibration over a period of 4 days. The percentage of time spent above 1.5, 1.75 and 2 times resting heart rate (RHR) represented all light-to-vigorous, moderate-to-vigorous and vigorous activity, respectively.
Data from a total of 643 non-diabetic individuals (319 men, 324 women) aged 50 to 75 years were analysed. In multivariate linear regression analyses, adjusting for age, sex and body fat percentage, PAEE was significantly associated with fasting insulin (pmol/l) (β = −0.875, p = 0.006). Time (% of total) spent above 1.75 × RHR and also time spent above 2 × RHR were both significantly associated with fasting insulin (β = −0.0109, p = 0.007 and β = −0.0365, p = 0.001 respectively), after adjusting for PAEE, age, sex and body fat percentage. Time spent above 1.5 × RHR was not significantly associated with fasting insulin in a similar model (β = −0.0026, p = 0.137).
The association between PAEE and fasting insulin level, a marker of insulin resistance, may be attributable to the time spent in moderate-to-vigorous and vigorous activity, but not to time spent in light-intensity physical activity.
PMCID: PMC2491413  PMID: 18488189
Activity intensity; Energy expenditure; Insulin resistance; Physical activity
23.  Secular trends in cholesterol lipoproteins and triglycerides and prevalence of dyslipidemias in an urban Indian population 
Coronary heart disease is increasing in urban Indian subjects and lipid abnormalities are important risk factors. To determine secular trends in prevalence of various lipid abnormalities we performed studies in an urban Indian population.
Successive epidemiological Jaipur Heart Watch (JHW) studies were performed in Western India in urban locations. The studies evaluated adults ≥ 20 years for multiple coronary risk factors using standardized methodology (JHW-1, 1993–94, n = 2212; JHW-2, 1999–2001, n = 1123; JHW-3, 2002–03, n = 458, and JHW-4 2004–2005, n = 1127). For the present analyses data of subjects 20–59 years (n = 4136, men 2341, women 1795) have been included. In successive studies, fasting measurements for cholesterol lipoproteins (total cholesterol, LDL cholesterol, HDL cholesterol) and triglycerides were performed in 193, 454, 179 and 252 men (n = 1078) and 83, 472, 195, 248 women (n = 998) respectively (total 2076). Age-group specific levels of various cholesterol lipoproteins, triglycerides and their ratios were determined. Prevalence of various dyslipidemias (total cholesterol ≥ 200 mg/dl, LDL cholesterol ≥ 130 mg/dl, non-HDL cholesterol ≥ 160 mg/dl, triglycerides ≥ 150 mg/dl, low HDL cholesterol <40 mg/dl, high cholesterol remnants ≥ 25 mg/dl, and high total:HDL cholesterol ratio ≥ 5.0, and ≥ 4.0 were also determined. Significance of secular trends in prevalence of dyslipidemias was determined using linear-curve estimation regression. Association of changing trends in prevalence of dyslipidemias with trends in educational status, obesity and truncal obesity (high waist:hip ratio) were determined using two-line regression analysis.
Mean levels of various lipoproteins increased sharply from JHW-1 to JHW-2 and then gradually in JHW-3 and JHW-4. Age-adjusted mean values (mg/dl) in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed a significant increase in total cholesterol (174.9 ± 45, 196.0 ± 42, 187.5 ± 38, 193.5 ± 39, 2-stage least-squares regression R = 0.11, p < 0.001), LDL cholesterol (106.2 ± 40, 127.6 ± 39, 122.6 ± 44, 119.2 ± 31, R = 0.11, p < 0.001), non-HDL cholesterol (131.3 ± 43, 156.4 ± 43, 150.1 ± 41, 150.9 ± 32, R = 0.12, p < 0.001), remnant cholesterol (25.1 ± 11, 28.9 ± 14, 26.0 ± 11, 31.7 ± 14, R = 0.06, p = 0.001), total:HDL cholesterol ratio (4.26 ± 1.3, 5.18 ± 1.7, 5.21 ± 1.7, 4.69 ± 1.2, R = 0.10, p < 0.001) and triglycerides (125.6 ± 53, 144.5 ± 71, 130.1 ± 57, 158.7 ± 72, R = 0.06, p = 0.001) and decrease in HDL cholesterol (43.6 ± 14, 39.7 ± 8, 37.3 ± 6, 42.5 ± 6, R = 0.04, p = 0.027). Trends in age-adjusted prevalence (%) of dyslipidemias in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed insignificant changes in high total cholesterol (26.3, 35.1, 25.6, 26.0, linear curve-estimation coefficient multiple R = 0.034), high LDL cholesterol ≥ 130 mg/dl (24.2, 36.2, 31.0, 22.2, R = 0.062), and high low HDL cholesterol < 40 mg/dl (46.2, 53.3, 55.4, 33.7, R = 0.136). Increase was observed in prevalence of high non-HDL cholesterol (23.0, 33.5, 27.4, 26.6, R = 0.026), high remnant cholesterol (40.1, 40.3, 30.1, 60.6, R = 0.143), high total:HDL cholesterol ratio ≥ 5.0 (22.2, 47.6, 53.2, 26.3, R = 0.031) and ≥ 4.0 (58.6, 72.5, 70.1, 62.0, R = 0.006), and high triglycerides (25.7, 28.2, 17.5, 34.2, R = 0.047). Greater correlation of increasing non-HDL cholesterol, remnant cholesterol, triglycerides and total:HDL cholesterol ratio was observed with increasing truncal obesity than generalized obesity (two-line regression analysis p < 0.05). Greater educational level, as marker of socioeconomic status, correlated significantly with increasing obesity (r2 men 0.98, women 0.99), and truncal obesity (r2 men 0.71, women 0.90).
In an urban Indian population, trends reveal increase in mean total-, non-HDL-, remnant-, and total:HDL cholesterol, and triglycerides and decline in HDL cholesterol levels. Prevalence of subjects with high total cholesterol did not change significantly while those with high non-HDL cholesterol, cholesterol remnants, triglycerides and total-HDL cholesterol ratio increased. Increasing dyslipidemias correlate significantly with increasing truncal obesity and obesity.
PMCID: PMC2579290  PMID: 18950504
24.  TV Viewing and Physical Activity Are Independently Associated with Metabolic Risk in Children: The European Youth Heart Study 
PLoS Medicine  2006;3(12):e488.
TV viewing has been linked to metabolic-risk factors in youth. However, it is unclear whether this association is independent of physical activity (PA) and obesity.
Methods and Findings
We did a population-based, cross-sectional study in 9- to 10-y-old and 15- to 16-y-old boys and girls from three regions in Europe (n = 1,921). We examined the independent associations between TV viewing, PA measured by accelerometry, and metabolic-risk factors (body fatness, blood pressure, fasting triglycerides, inverted high-density lipoprotein (HDL) cholesterol, glucose, and insulin levels). Clustered metabolic risk was expressed as a continuously distributed score calculated as the average of the standardized values of the six subcomponents. There was a positive association between TV viewing and adiposity (p = 0.021). However, after adjustment for PA, gender, age group, study location, sexual maturity, smoking status, birth weight, and parental socio-economic status, the association of TV viewing with clustered metabolic risk was no longer significant (p = 0.053). PA was independently and inversely associated with systolic and diastolic blood pressure, fasting glucose, insulin (all p < 0.01), and triglycerides (p = 0.02). PA was also significantly and inversely associated with the clustered risk score (p < 0.0001), independently of obesity and other confounding factors.
TV viewing and PA may be separate entities and differently associated with adiposity and metabolic risk. The association between TV viewing and clustered metabolic risk is mediated by adiposity, whereas PA is associated with individual and clustered metabolic-risk indicators independently of obesity. Thus, preventive action against metabolic risk in children may need to target TV viewing and PA separately.
A study of over 1,900 European children showed that TV viewing and physical activity in children are separately associated with obesity and metabolic risk.
Editors' Summary
Childhood obesity is a rapidly growing problem. Twenty-five years ago, overweight children were rare. Now, 155 million of the world's children are overweight, and 30–45 million are obese. Both conditions are diagnosed by comparing a child's body mass index (BMI; weight divided by height squared) with the average BMI for their age and sex. Being overweight during childhood is worrying because it is one of the so-called metabolic-risk factors that increase the chances of developing diabetes, heart problems, or strokes later in life. Other metabolic-risk factors are fatness around the belly, blood-fat disorders, high blood pressure, and problems with how the body uses insulin and blood sugar. Until recently, like obesity, these other metabolic-risk factors were seen only in adults, but now they are becoming increasingly common in children. In the US, 1 in 20 adolescents has metabolic syndrome—three or more of these risk factors. Environmental and behavioural changes have probably contributed to the increase in metabolic syndrome in children. As a group, they tend to be less physically active nowadays and they eat bigger portions of energy-dense foods more often. Increased TV viewing during childhood (and the use of other media such as computer games) has also been linked to increased obesity and to poorer health as an adult.
Why Was This Study Done?
One popular theory is that TV viewing may affect obesity and other metabolic-risk factors by displacing PA. Instead of playing in the yard after school, the theory suggests, children laze about in front of the TV. However, there is limited evidence to support this idea, and health professionals need to know whether TV viewing and PA are related, and how they affect metabolic-risk factors, in order to improve children's health. In this study, the researchers examined the associations between TV viewing, PA, and metabolic-risk factors in European children.
What Did the Researchers Do and Find?
The researchers enrolled nearly 2,000 children in two age groups from three areas in Europe. They measured the children's height and weight, estimated how fat they were by measuring skin fold thickness, measured their blood pressure, and examined the levels of glucose, insulin, and different fats in their blood. The children completed a computer questionnaire about the lengths of time for which they watched TV and how often they ate while doing so, and their PA was measured using a device called an accelerometer that each child wore for four days. When these data were analyzed statistically, the researchers found that TV viewing was slightly associated with clustered metabolic risk (the average of the individual metabolic-risk factors). This association was due to an association between TV viewing and obesity—the children who watched most TV tended to be the fattest children. However, TV viewing was not related to PA. The most active children were not necessarily those who watched least TV. Most importantly, PA was related to all individual risk factors except for obesity and with clustered metabolic risk. These associations were independent of obesity.
What Do These Findings Mean?
These results suggest that TV viewing does not damage children's health by displacing PA as popularly believed. The finding that the association between TV viewing and clustered metabolic-risk factors is mediated by obesity suggests that targeting behaviours like eating while watching TV might be a good way to improve children's health. Indeed, the researchers provide some evidence that eating while watching TV is associated with being overweight, but the results of this post hoc analysis—one that was not planned in advance—need to be confirmed. Another limitation of the study is the possibility that the children inaccurately reported their TV watching habits. Also, because measurements of metabolic-risk factors were made only once, it is impossible to say whether TV viewing or lack of PA actually causes an increase in metabolic-risk factors.
Nevertheless, these results strongly suggest that promoting PA is beneficial in relation to metabolic-risk factors, but less so in relation to obesity in childhood. TV viewing and PA should be treated as separate targets in programs designed to reverse the obesity and metabolic-syndrome epidemic in children.
Additional Information.
Please access these Web sites via the online version of this summary at
US Centers for Disease Control and Prevention, information on overweight and obesity
International Obesity Taskforce, information on obesity and its prevention, particularly in childhood
Global Prevention Alliance, details of international efforts to halt the obesity epidemic and its associated chronic diseases
American Heart Association, information for patients and professionals on metabolic syndrome and children's health
PMCID: PMC1705825  PMID: 17194189
25.  Distinct Characteristics of Circulating Vascular Endothelial Growth Factor-A and C Levels in Human Subjects 
PLoS ONE  2011;6(12):e29351.
The mechanisms that lead from obesity to atherosclerotic disease are not fully understood. Obesity involves angiogenesis in which vascular endothelial growth factor-A (VEGF-A) plays a key role. On the other hand, vascular endothelial growth factor-C (VEGF-C) plays a pivotal role in lymphangiogenesis. Circulating levels of VEGF-A and VEGF-C are elevated in sera from obese subjects. However, relationships of VEGF-C with atherosclerotic risk factors and atherosclerosis are unknown. We determined circulating levels of VEGF-A and VEGF-C in 423 consecutive subjects not receiving any drugs at the Health Evaluation Center. After adjusting for age and gender, VEGF-A levels were significantly and more strongly correlated with the body mass index (BMI) and waist circumference than VEGF-C. Conversely, VEGF-C levels were significantly and more closely correlated with metabolic (e.g., fasting plasma glucose, hemoglobin A1c, immunoreactive insulin, and the homeostasis model assessment of insulin resistance) and lipid parameters (e.g., triglycerides, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C)) than VEGF-A. Stepwise regression analyses revealed that independent determinants of VEGF-A were the BMI and age, whereas strong independent determinants of VEGF-C were age, triglycerides, and non-HDL-C. In apolipoprotein E-deficient mice fed a high-fat-diet (HFD) or normal chow (NC) for 16 weeks, levels of VEGF-A were not significantly different between the two groups. However, levels of VEGF-C were significantly higher in HFD mice with advanced atherosclerosis and marked hypercholesterolemia than NC mice. Furthermore, immunohistochemistry revealed that the expression of VEGF-C in atheromatous plaque of the aortic sinus was significantly intensified by feeding HFD compared to NC, while that of VEGF-A was not. In conclusion, these findings demonstrate that VEGF-C, rather than VEGF-A, is closely related to dyslipidemia and atherosclerosis.
PMCID: PMC3243691  PMID: 22206010

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