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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.  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
5.  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
6.  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
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.  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
9.  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
10.  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
11.  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
12.  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
13.  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
14.  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
15.  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
16.  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
17.  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
18.  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
19.  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
20.  Early Emergence of Ethnic Differences in Type 2 Diabetes Precursors in the UK: The Child Heart and Health Study in England (CHASE Study) 
PLoS Medicine  2010;7(4):e1000263.
Peter Whincup and colleagues carry out a cross-sectional study examining ethnic differences in precursors of of type 2 diabetes among children aged 9–10 living in three UK cities.
Adults of South Asian origin living in the United Kingdom have high risks of type 2 diabetes and central obesity; raised circulating insulin, triglyceride, and C-reactive protein concentrations; and low HDL-cholesterol when compared with white Europeans. Adults of African-Caribbean origin living in the UK have smaller increases in type 2 diabetes risk, raised circulating insulin and HDL-cholesterol, and low triglyceride and C-reactive protein concentrations. We examined whether corresponding ethnic differences were apparent in childhood.
Methods and Findings
We performed a cross-sectional survey of 4,796 children aged 9–10 y in three UK cities who had anthropometric measurements (68% response) and provided blood samples (58% response); ethnicity was based on parental definition. In age-adjusted comparisons with white Europeans (n = 1,153), South Asian children (n = 1,306) had higher glycated haemoglobin (HbA1c) (% difference: 2.1, 95% CI 1.6 to 2.7), fasting insulin (% difference 30.0, 95% CI 23.4 to 36.9), triglyceride (% difference 12.9, 95% CI 9.4 to 16.5), and C-reactive protein (% difference 43.3, 95% CI 28.6 to 59.7), and lower HDL-cholesterol (% difference −2.9, 95% CI −4.5 to −1.3). Higher adiposity levels among South Asians (based on skinfolds and bioimpedance) did not account for these patterns. Black African-Caribbean children (n = 1,215) had higher levels of HbA1c, insulin, and C-reactive protein than white Europeans, though the ethnic differences were not as marked as in South Asians. Black African-Caribbean children had higher HDL-cholesterol and lower triglyceride levels than white Europeans; adiposity markers were not increased.
Ethnic differences in type 2 diabetes precursors, mostly following adult patterns, are apparent in UK children in the first decade. Some key determinants operate before adult life and may provide scope for early prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Worldwide, nearly 250 million people have diabetes, and the number of people affected by this chronic disease is increasing rapidly. Diabetes is characterized by dangerous amounts of sugar (glucose) in the blood. Blood sugar levels are normally controlled by insulin, a hormone that the pancreas releases when blood sugar levels rise after eating (digestion of food produces glucose). In people with type 2 diabetes (the most common type of diabetes), blood sugar control fails because the fat and muscle cells that usually respond to insulin by removing sugar from the blood become less responsive to insulin (insulin resistant). Type 2 diabetes can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. Long-term complications of diabetes include kidney failure, blindness, nerve damage, and an increased risk of developing cardiovascular problems, including heart disease and stroke.
Why Was This Study Done?
South Asians and African-Caribbeans living in Western countries tend to have higher rates of type 2 diabetes than host populations. South Asian adults living in the UK, for example, have a 3-fold higher risk of developing type 2 diabetes than white Europeans. They also have higher fasting blood levels of glucose, insulin and triglycerides (a type of fat), higher blood levels of “glycated hemoglobin” (HbA1c; an indicator of average of blood-sugar levels over time), more body fat (increased adiposity), raised levels of a molecule called C-reactive protein, and lower levels of HDL-cholesterol (another type of fat) than white Europeans. Most of these “diabetes precursors” (risk factors) are also seen in black African-Caribbean adults living in the UK except that individuals in this ethnic group often have raised HDL-cholesterol levels and low triglyceride levels. Ethnic differences in type 2 diabetes precursors are also present in adolescents, but the extent to which they are present in childhood remains unclear. Knowing this information could have implications for diabetes prevention. In this population-based study, therefore, the researchers investigate patterns of diabetes precursors in 9- to 10-year-old UK children of white European, South Asian, and black African-Caribbean origin.
What Did the Researchers Do and Find?
The researchers enrolled nearly 5,000 children (including 1,153 white European, 1,306 South Asian and 1,215 black African-Caribbean children) from primary schools with high prevalences of ethnic minority pupils in London, Birmingham, and Leicester in the Child Heart and Health study in England (CHASE). They measured and weighed more than two-thirds of the enrolled children and determined their adiposity. They also took blood samples for measurement of diabetes precursors from nearly two-thirds of the children. The recorded ethnicity of each child was based on parental definition. The researchers' analysis of these data showed that, compared with white Europeans, South Asian children had higher levels of HbA1c, insulin, triglycerides, and C-reactive protein but lower HDL-cholesterol levels. In addition, they had higher adiposity levels than the white European children, but this did not account for the observed differences in the other diabetes precursors. Black African-Caribbean children also had higher levels of HbA1c, insulin, and C-reactive protein than white European children, although the differences were smaller than those between South Asians and white Europeans. Similar to black African-Caribbean adults, however, children of this ethnic origin had higher HDL-cholesterol and lower triglyceride levels than white Europeans.
What Do These Findings Mean?
These findings indicate that ethnic differences in diabetes precursors are already present in apparently healthy children before they are 10 years old. Furthermore, most of the ethnic differences in diabetes precursors seen among the children follow the pattern seen in adults. Although these findings need confirming in more children, they suggest that the ethnic differences in type 2 diabetes susceptibility first described in immigrants to the UK are persisting in UK-born South Asian and black African-Caribbean children. Most importantly, these findings suggest that some of the factors thought to be responsible for ethnic differences in type 2 diabetes—for example, varying levels of physical activity and dietary differences—are operating well before adult life. Interventions that target these factors early could, therefore, offer good opportunities for diabetes prevention in high-risk ethnic groups, provided such interventions are carefully tailored to the needs of these groups.
Additional Information
Please access these Web sites via the online version of this summary at
The International Diabetes Federation provides information about all aspects of diabetes (in English, French and Spanish)
The US National Diabetes Information Clearinghouse provides detailed information about diabetes for patients, health-care professionals and the general public, including information on diabetes in specific US populations (in English and Spanish)
The UK National Health Service also provides information for patients and carers about type 2 diabetes (in several languages)
MedlinePlus provides links to further resources and advice about diabetes (in English and Spanish)
The US Agency for Healthcare Research and Quality has a fact sheet on diabetes disparities among racial and ethnic minorities
PMCID: PMC2857652  PMID: 20421924
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.  Prehypertension and Cardiovascular Risk Factors in Children and Adolescents Participating in the Community-Based Prevention Education Program Family Heart Study 
Because prehypertension identifies children most at risk for the development of future hypertensive disease, the purpose of this study was, to examine the association of prehypertension with risk factors for cardiovascular disease (CVD) in a large sample of youths participating in the community-based prevention education program family heart study.
We estimated blood pressure and body mass index (BMI) for age and the lipid profile in terms of total cholesterol (TC), low-density-lipoprotein-cholesterol (LDL-C), high-density-lipoprotein-cholesterol (HDL-C), non-HDL-C, triglycerides (TG) and the LDL-C to HDL-C ratio.
Among 10,841 (5,628 males) children and adolescents 1,587 (14.6%) had prehypertension (85th to <95th percentile). This was strongly affected by weight, resulting in 19.7% in overweight (BMI ≥85th percentile) and 23.7% in obese (>95th percentile) youth. The prevalence of dyslipidemia was similar in prehypertensive boys and girls in terms of LDL-C 11.2% versus 11.8%, non HDL-C 11.9% versus 14.3%, TG 2.4% versus 2.7% and for low HDL-C 2.1% versus 2.3%. The prevalence of low HDL-C increased from 2.1% in non-overweight, through 3.9% in overweight to 5.2% in obese youth and of elevated TG from 1.2% via 4.5% to 6.5% respectively. The number of risk factors is affected by BMI. Significant associations between prehypertension and CVD risk factors were observed in boys and girls for overweight/obesity odds ratios (OR 2.0/2.4), for hypertriglyceridemia (OR 1.9/2.0), for high non HDL-C (OR 1.4/1.4) and for elevated LDL-C (OR 1.3/1.1).
Prehypertension was significantly associated with overweight, obesity and dyslipidemia in 10,841 children and adolescents.
PMCID: PMC3990916  PMID: 24791192
Cardiovascular risk factors; prehypertension; urban children and adolescents
24.  Association between general and central adiposity in childhood, and change in these, with cardiovascular risk factors in adolescence: prospective cohort study 
Objectives To examine the prospective associations between body mass index (BMI), waist circumference, and fat mass in childhood and cardiovascular risk factors at age 15-16.
Design Prospective cohort study.
Setting Avon Longitudinal Study of Parents and Children.
Participants 5235 children aged 9-12 at start of study.
Main exposures BMI, waist circumference, and fat mass determined by dual energy x ray absorptiometry, assessed at age 9-12 and at age 15-16.
Main outcome measures Systolic and diastolic blood pressure and concentrations of fasting glucose, insulin, triglycerides, low density lipoprotein cholesterol, and high density lipoprotein cholesterol assessed at age 15-16.
Results In girls a 1 SD greater BMI at age 9-12 was associated with cardiovascular risk factors at age 15-16 in fully adjusted models: odds ratio 1.23 (95% confidence interval 1.10 to 1.38) for high systolic blood pressure (≥130 mm Hg); 1.19 (1.03 to 1.38) for high concentration of low density lipoprotein cholesterol (≥2.79 mmol/l); 1.43 (1.06 to 1.92) for high concentration of triglycerides (≥1.7 mmol/l); 1.25 (1.08 to 1.46) for low concentration of high density lipoprotein cholesterol (<1.03 mmol/l); and 1.45 (1.22 to 1.73) for high concentration of insulin (≥16.95 IU/l). Equivalent results in boys were 1.24 (1.13 to 1.37) for systolic blood pressure; 1.30 (1.07 to 1.59) for low density lipoprotein cholesterol; 1.96 (1.51 to 2.55) for triglycerides; 1.39 (1.22 to 1.57) for high density lipoprotein cholesterol, and 1.84 (1.56 to 2.17) for insulin. BMI was associated with high fasting glucose (≥5.6 mmol/l) only in boys (1.18, 1.03 to 1.36). With these binary outcomes there was statistical evidence that associations differed between girls and boys for fasting glucose (P=0.03) and insulin (P<0.001). When risk factors were examined as continuous outcomes there was evidence for stronger associations of BMI with more adverse levels in boys than girls for fasting insulin, glucose, and triglyceride concentrations (all interaction P≤0.03). BMI, waist circumference, and fat mass were all strongly correlated with each other (r=0.89-0.94), and associations of the three with cardiovascular outcomes were of similar magnitude with statistical evidence of consistency in associations (all P>0.2 for heterogeneity). When waist circumference or fat mass or both were added to models including BMI they did not increase the variation in cardiovascular risk factors already explained by BMI and confounders alone. Girls who were overweight/obese at age 9-12 but were normal weight by 15-16 had similar odds of adverse levels of risk factors to those who were normal weight at both ages. In boys odds of high systolic blood pressure, high concentrations of triglycerides and insulin, and low concentrations of high density lipoprotein cholesterol remained higher in this group compared with those who were normal weight at both ages but were lower than in those who remained overweight/obese at both ages.
Conclusions Measurements of waist circumference or directly assessed fat mass in childhood do not seem to be associated with cardiovascular risk factors in adolescence any more strongly than BMI. Girls who favourably alter their overweight status between childhood and adolescence have cardiovascular risk profiles broadly similar to those who were normal weight at both time points, but boys who change from overweight to normal show risk factor profiles intermediate between those seen in boys who are normal weight at both ages or overweight at both ages.
PMCID: PMC2992109  PMID: 21109577
25.  The relationship between walking speed and changes in cardiovascular risk factors during a 12-day walking tour to Santiago de Compostela: a cohort study 
BMJ Open  2012;2(3):e000875.
Physical exercise has beneficial effects on cardiovascular risk factors. Knowledge about the effect of exercise intensity, specifically walking speed, on cardiovascular risk factors is limited. We report the relationship between walking speed and changes in cardiovascular risk factors in participants of a 12-day walking tour to Santiago de Compostela.
Prospective cohort study.
Single-centre study with healthy middle-aged volunteers.
Healthy middle-aged men (n=15) and women (n=14). Subjects using lipid-lowering medication were excluded.
Participants walked 281±10 km of the classical route to Santiago de Compostela in 12 days in 2009.
Primary and secondary outcome measures
Walking speed was recorded and blood pressure, weight, waist circumference, lipids and glucose were measured every other day. Changes in risk factors were compared between gender-pooled groups with faster and slower walking speed. Second, the relationship between walking speed and changes in risk factors was quantified using a linear mixed effects model.
In the faster walking speed (4.6±0.2 km/h) group, high-density lipoprotein cholesterol (HDL-c) increased more than in the slower walking speed (4.1±0.2 km/h) group (difference in change between groups: 0.20; 95% CI −0.02 to 0.42 mmol/l), while low-density lipoprotein cholesterol (LDL-c) and total cholesterol decreased more in the slower walking speed group (differences in changes between groups: LDL-c: −0.50; 95% CI −0.88 to −0.12 mmol/l and total cholesterol: −0.75; 95% CI −1.19 to −0.31 mmol/l). A 1 km/h higher walking speed was related to an increase in HDL-c (0.24; 95% CI 0.12 to 0.30 mmol/l), LDL-c (0.18; 95% CI −0.16 to 0.42 mmol/l) and total cholesterol (0.36; 95% CI 0.12 to 0.60 mmol/l), adjusted for age, gender, smoking, body mass index and heart rate, during the whole walking tour.
Walking the same distance faster improves HDL-c more, while LDL-c and total cholesterol decrease more with lower walking speed independent of changes in body weight in healthy middle-aged subjects.
Article summary
Article focus
Physical exercise has beneficial effects on cardiovascular risk factors; however, the knowledge about the effect of exercise intensity, specifically walking speed, on cardiovascular risk factors is limited.
We report the relationship between walking speed and changes in cardiovascular risk factors in participants of a 12-day walking tour to Santiago de Compostela.
Key messages
In subjects walking a 12-day walking tour to Santiago de Compostela, with long daily stages:walking the same distance with higher walking speed was related to a higher increase in HDL-c, while walking with lower walking speed was related to larger decreases in LDL-c and total cholesterol, adjusted for age, gender, smoking, body mass index and heart rate.there was no relationship between walking speed and changes in weight, waist circumference, blood pressure, triglycerides or glucose.
Strengths and limitations of this study
All subjects walked the same overall distance, walking speed was measured and measurements of cardiovascular risk factors were conducted every other day.
This is a small study with 29 participants walking 281 km in 12 days. Whether the results of this study can be extrapolated to less exercise, and other types of exercise is not known.
PMCID: PMC3353125  PMID: 22581795

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