Evert G. Schouten

Low Heart Rate Variability in a 2-Minute Rhythm Strip Predicts Risk of Coronary Heart Disease and Mortality From Several Causes The ARIC Study

BackgroundLow heart rate variability (HRV) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease (CHD) in the general population. Methods and ResultsWe studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD, aged 45 to 65, by using the case-cohort design. At baseline, in 1987 to 1989, 2-minute rhythm strips were recorded. Time-domain measures of HRV were determined in a random sample of 900 subjects, for all subjects with incident CHD (395 subjects), and for all deaths (443 subjects) that occurred through 1993. Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design. Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death. The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors. ConclusionsLow HRV was associated with increased risk of CHD and death from several causes. It is hypothesized that low HRV is a marker of less favorable health.

QT interval prolongation predicts cardiovascular mortality in an apparently healthy population.

BackgroundIn myocardial infarction patients, heart rate-adjusted QT interval (QT), an electrocardiographic indicator of sympathetic balance, is prognostic for survival. Methods and ResultsIn a 28-year follow-up, the association between QT, and all-cause, cardiovascular, and ischemic heart disease mortality was studied in a population of 3,091 apparently healthy Dutch civil servants and their spouses, aged 40–65 years, who participated in a medical examination during 1953–1954. Moderate (QTc, 420–440 msec) and extensive (QTc, more than 440 msec) QTc prolongations significantly predict all-cause mortality during the first 15 years among men (adjusted respective relative risks [RRs], 1.5 and 1.7) and among women (RRs, 1.7 and 1.6). In men, cardiovascular (RRs, 1.6 and 1.8) and ischemic heart disease mortality (RRs, 1.8 and 2.1) mainly account for this association. In women, the association cannot be attributed specifically to cardiovascular and ischemic heart disease mortality. RRs for a subpopulation without any sign of heart disease at baseline are similar. The same is observed for QT, prolongation after light exercise, although in this situation most associations are not statistically significant, probably because of smaller numbers in the QTc prolongation categories. ConclusionsOur results suggest that QT, contributes independently to cardiovascular risk. If autonomic imbalance is an important mechanism, it might be speculated that changes in life-style (e.g., with regard to physical exercise and smoking) may have a preventive impact.

Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised double blind, controlled trial

BACKGROUND Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the effect of folic acid on markers of atherosclerosis in men and women aged 50-70 years with raised plasma total homocysteine and normal serum vitamin B12 at screening, we report here the findings for the secondary endpoint: the effect of folic acid supplementation on cognitive performance. METHODS Our randomised, double blind, placebo controlled study took place between November, 1999, and December, 2004, in the Netherlands. We randomly assigned 818 participants 800 mug daily oral folic acid or placebo for 3 years. The effect on cognitive performance was measured as the difference between the two groups in the 3-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov with trial number NCT00110604. FINDINGS Serum folate concentrations increased by 576% (95% CI 539 to 614) and plasma total homocysteine concentrations decreased by 26% (24 to 28) in participants taking folic acid compared with those taking placebo. The 3-year change in memory (difference in Z scores 0.132, 95% CI 0.032 to 0.233), information processing speed (0.087, 0.016 to 0.158) and sensorimotor speed (0.064, -0.001 to 0.129) were significantly better in the folic acid group than in the placebo group. INTERPRETATION Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.

Validity of the Physical Activity Scale for the Elderly (PASE): according to energy expenditure assessed by the doubly labeled water method.

The study investigates the validity of the Physical Activity Scale for the Elderly (PASE) in 21 Dutch elderly men and women. The PASE is an easily scored, brief questionnaire for elderly, suitable for large epidemiologic studies. The PASE score was compared with physical activity measured with the doubly labeled water method. The correlation coefficient of the PASE score with the residuals from the regression analysis using total energy expenditure as dependent and resting metabolic rate as independent variate was 0.58 (95% CI = 0.50-0.81). Women had greater engagement in extremely high scoring activities as housework and taking care of others, resulting in higher PASE scores than men (97.9 and 71.9). The higher scores in women were not linked to higher activity levels, which suggests that the mentioned activities may be overvalued. Sex specific correlation coefficients were 0.79 (CI = 0.32-0.95) and 0.68 (CI = 0.15-0.90) for men and women, respectively. In conclusion, the PASE proved to be a reasonable valid method to classify healthy elderly men and women into categories of physical activity. Some possible refinements were suggested, which may improve the accuracy of the PASE questionnaire.

Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study.

BackgroundHeart-rate-adjusted QT-interval (QTc) is prognostic of sudden death in myocardial infarction patients. So far, population studies have yielded conflicting results on the predictive value of QTc for coronary heart disease morbidity and mortality. Therefore, we investigated this in a longitudinal study of middle-aged and elderly men. Methods and ResultsFrom 1960 to 1985, 877 middle-aged men were followed and repeatedly examined in the Zutphen Study. In 1985 the remaining cohort was extended to 835 elderly men from the same birth cohort and followed until 1990. Men with prolonged QTc (420 ms1/2 or more) had a higher risk of myocardial infarction and coronary heart disease death relative to men with QTc less than 385 ms1/2. Ageadjusted coronary heart disease mortality rate ratios were 4.3 (95% confidence interval, 1.3 to 13.8) in middle-aged men and 3.3 (95% confidence interval, 1.0 to 11.6) in elderly men. These associations could not be attributed to prevalent heart disease and were independent of other cardiovascular risk factors. ConclusionsThese results indicate that within the normal range of QTc in the general population, men with long QTc are at higher risk for coronary heart disease. Because QTc is easily determined, it may provide a valuable contribution to risk stratification.

Duration of shiftwork related to body mass index and waist to hip ratio

OBJECTIVE: An elevated cardiovascular disease risk for shiftworkers has frequently been reported, however, the mechanism is still unknown. Changes in eating habits, in physical activity or metabolic factors could be involved. In this study we assessed the relationship between body mass index (BMI) as a possible indicator of changed eating habits or metabolic involvement and duration of shiftwork.DESIGN: Data from an ongoing cohort study among 377 shiftworkers and non-shiftworking controls, all starting in a new job were used. Anthropometric measurements were carried out at the start of the assignment. Job history was obtained by a questionnaire.RESULTS: A positive relationship was observed between BMI and waist to hip ratio (WHR) and duration of shiftwork experience, with an adjustment for age. The linear regression coefficients, with additional adjustments for sex, smoking status, physical activity and educational level were 0.12 kg/m2 per y in shiftwork for BMI (P<0.05) and 0.0016 per y in shiftwork for WHR (P<0.05).CONCLUSIONS: These results suggest a relationship between years worked in shifts with BMI and WHR for both males and females. Whether this might reflect an effect of changed dietary habits or a metabolic effect is not yet clear.

Within-subject variability of flow-mediated vasodilation of the brachial artery in healthy men and women: implications for experimental studies

Flow-mediated vasodilation (FMD) of the brachial artery is used as a marker of cardiovascular disease risk. It is defined as the percentage dilation from the baseline diameter in response to a provoked increase in blood flow. The within-subject variability, crucial in the design of trials with FMD as an endpoint, appears to vary widely between studies. We assessed the analytical and within-subject variability of FMD in healthy subjects and estimated the number of subjects needed to detect various treatment effects in intervention trials and observational studies. FMD was assessed with B-mode high-resolution ultrasound (US). A total of 13 volunteers were measured on six occasions, after they had fasted overnight. Within-subject variability was assessed from all six scans per subject. Analytical variation or reading variation was assessed by reading one scan of each subject twice by one observer. The mean (+/-SD) FMD was 5.60 +/- 2.15 FMD% of the baseline diameter. The within-subject SD was 2.8 FMD%, resulting in a coefficient of variation (CV) of 2.8/5.6 x 100% = 50.3%. The CVs for the baseline and maximum diameter were much smaller: 4.8% (SD 0.193 mm at a mean of 4.060 mm) for the baseline and 5.2% (SD 0.222 mm at a mean of 4.285 mm) for the maximum. The CV for reading variation was 34%. The number of subjects needed to detect a treatment difference of 2 FMD% with a probability of 0.05 and a power of 0.80 would be 31 in a crossover design and 62 per group in a parallel design for comparison of group changes. We conclude that the within-subject variability of FMD is large, about 50% of the mean response. This includes biologic and reading variation. Repeated measurements and repeated readings of recorded measurements are recommended to reduce variability.

Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators

AIMS To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. METHODS AND RESULTS We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79). CONCLUSION These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.

Plasminogen activator inhibitor-type 1: its plasma determinants and relation with cardiovascular risk

The habitual level of PAI-1 is influenced by many factors, of which obesity and insulin resistance are the most important. It is possible to reduce plasma PAI-1 by changes in life style, e.g. weight reduction and physical activity. Data on potential interactions between environmental and metabolic variables on one hand, and the 4G/5G-polymorphism on the other hand, are still scarce. It becomes more and more clear that PAI-1 may possibly not be a major (causal) factor in cardiovascular disease, but its role in inflammation deserves further attention. In the presence of the 4G-allele not only the PAI-1 response was more pronounced, but also the response of other acute-phase reactants, which implies that the increases of these reactants are secondary to the increase in PAI-1. A myocardial infarction also provokes an acute phase response. It can thus be hypothesized that the 4G-allele might exacerbate tissue injury during the acute phase after a myocardial infarction, and thereby negatively affect the prognosis.

Inverse association between dairy intake and hypertension: the Rotterdam Study

BACKGROUND Little is known about the effect of different types of dairy food products on the development of hypertension. OBJECTIVE The objective was to determine whether the incidence of hypertension in older Dutch subjects is associated with intake of dairy products. DESIGN We examined the relation between dairy intake and incident hypertension in 2245 participants of the Rotterdam Study aged > or =55 y with complete dietary and blood pressure data, who were free of hypertension at baseline (1990-1993). Blood pressure was reexamined in 1993-1995 and in 1997-1999. Hazard ratios (HRs) with 95% CIs for 2- and 6-y incidence of hypertension were obtained in quartiles of energy-adjusted dairy intake, with adjustment for age, sex, BMI, smoking, educational level, dietary factors, and intake of alcohol and total energy. RESULTS Risk of hypertension after 2 y of follow-up (664 incident cases) was inversely associated with dairy product intake. After adjustment for confounders, HRs (95% CIs) were 1.00, 0.82 (0.67, 1.02), 0.67 (0.54, 0.84), and 0.76 (0.61, 0.95) in consecutive quartiles of total dairy product intake (P for trend = 0.008). Corresponding HRs for low-fat dairy products were 1.00, 0.75 (0.60, 0.92), 0.77 (0.63, 0.96), and 0.69 (0.56, 0.86) (P for trend = 0.003). Analysis of specific types of dairy products showed an inverse association with milk and milk products (P for trend = 0.07) and no association with high-fat dairy or cheese (P > 0.6). After 6 y of follow-up (984 incident cases), the associations with hypertension were attenuated to risk reductions of approximately 20% for both total and low-fat dairy products between the extreme quartiles of intake (P for trend = 0.07 and 0.09, respectively). CONCLUSION Intake of low-fat dairy products may contribute to the prevention of hypertension at an older age.