European Journal of Preventive Cardiology

Background Improved endothelial function may contribute to the beneficial effects of cholesterol lowering therapy in patients with coronary artery disease (CAD), but results of the effect of statin therapy on endothelial function are disparate in these patients. Exercise training has been reported to improve endothelial function of patients at risk of or with established CAD. The goal of the study was to compare the effect of mild exercise training or statin therapy on forearm endothelial function in CAD patients with average cholesterol levels.

Design and methods Twenty-eight sedentary male patients with angiographically documented CAD and average pretreatment total plasma cholesterol levels (5.1±0.9 mmol/l) aged 42–75 years were included. They were randomly assigned in a 2:1 order to either statin therapy (pravastatin, 40 mg daily) or exercise training therapy (mild endurance exercise three or more times a week). The effects of 10 weeks of either treatment on endothelium-dependent and independent vasodilation of forearm resistance vessels was assessed by plethysmography. Cardiopulmonary exercise testing was performed at baseline and after 10 weeks.

Results Ten weeks of pravastatin therapy significantly reduced low-density lipoprotein cholesterol (from 3.8±0.6 to 3.1±0.6 mmol/l at study end, P=0.04) and the ratio of total to high-density lipoprotein cholesterol (from 4.9±0.8 to 3.7±0.7 mmol/l, P=0.002). Exercise training did not significantly modify the lipid profile. Peak oxygen consumption, maximal achieved workload and exercise duration tended to improve in the exercise training group but remained unchanged in the pravastatin-treated group. Neither 10 weeks of pravastatin nor mild endurance exercise training improved endothelium-dependent or independent vasomotor function in forearm resistance vessels.

Conclusions In patients with CAD and average cholesterol levels, 10 weeks of treatment with mild endurance exercise training or with pravastatin failed to improve endothelium-dependent or independent vasomotor function in forearm resistance vessels.

Background Chronic heart failure (CHF) is a serious condition that is associated with impaired health status and a high prevalence of depressive symptoms. To date, little is known about the determinants of health status and depressive symptoms in CHF. Therefore, the aim of this study was to assess whether Type D personality is associated with impaired health status and increased depressive symptoms in heart failure patients, independent of disease characteristics.

Methods Eighty-four patients (63 men and 21 women, mean age=65.9±12.1 years) with systolic CHF completed four questionnaires to assess Type D personality (14-item Type D Personality Scale [DS14]), health status (Minnesota Living with Heart Failure Questionnaire [MLWHFQ]), depressive symptoms (Center for Epidemiological Studies Depression Scale [CES-D]) and mood status (Global Mood Scale [GMS]) when visiting an outpatient heart failure clinic. Information on clinical variables was obtained from patients’ medical records.

Results Type D patients were more likely to experience impairment in health status (18/38=47%) as compared to non-Type Ds (11/46=24%), P=0.027. They also more often reported symptoms of depression; namely 18 of 38=47% versus 6 of 46=13%, P=0.001. When controlling for severity and etiology of CHF, age and gender, Type D remained a significant associate of impaired health status [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.12–7.78] and depressive symptoms (OR 6.3, 95% CI 2.08–19.12).

Conclusions Type D was associated with impaired health status and increased depressive symptoms in CHF patients. These preliminary findings demonstrate the value of including personality factors in CHF research.

Background To determine the prevalence and associated risk factors of cardiovascular diseases in a rural adult black population from Limpopo Province in South Africa.

Design A cross-sectional study.

Methods A sample of 1608 women and 498 men aged 30 years and above participated in the study. Sociodemographic data, anthropometric measures (body mass index, waist/hip ratio), blood pressure and biochemical risk factors were measured. A global cardiovascular disease (CVD) risk profile was developed.

Results There was a high prevalence of tobacco use for men (57%) and women (35.4%), with women (28.1%) predominantly using smokeless tobacco. Alcohol use was very common in men (57.2%). Women weighed a great deal more than men, and 51.7% were either overweight or obese. Diabetes was diagnosed in 8.8 and 8.5% of women and men, respectively. High-density lipoprotein-cholesterol was relatively high, whereas 42.3% of women and 28.5% of men had low-density lipoprotein-cholesterol levels of 3 mmol/l or more. Hypertension (blood pressure ≥ 140/90 mmHg) was found in 25.5% of women and 21.6% of men. According to the Framingham formulae, 18.9% of women and 32.1% of men had a 20% or higher chance of having a CVD event in the next 10 years.

Conclusions There was a high prevalence of chronic disease risk factors in the rural, poor black community in Limpopo, South Africa. Consequently, the population had a higher than expected risk of developing a CVD event in the following 10 years when compared with similar studies in black Africans.

Objectives To determine any differences in the urinary excretion and dietary intake of sodium, potassium, magnesium and calcium intake in three South African ethnic groups, and to assess whether the blood pressure–cation association varies according to ethnic status.

Design A cross-sectional study of 325 black, white and mixed-ancestry men and women, conveniently sampled in Cape Town. Twenty-four-hour urine samples were collected on three separate occasions for assessment of urinary electrolytes, and three 24-h dietary recalls for the corresponding urine collection times were administered by two trained fieldworkers. Para-amino benzoic acid was used as a marker of the completeness of urine collection.

Results Mean urinary sodium values equate to a daily salt (sodium chloride) intake of 7.8, 8.5 and 9.5 g in black, mixed-ancestry and white individuals, respectively. In normotensive individuals, black and mixed-ancestry subjects had significantly lower median urinary sodium concentrations than white subjects, but these differences were not evident between black and white hypertensive subjects. No ethnic differences were found for urinary potassium, except for mixed-ancestry normotensive individuals having a lower excretion than white normotensive individuals. Urinary magnesium excretion did not differ across ethnic groups. In both normotensive and hypertensive individuals, urinary calcium concentrations differed between all three groups, with black subjects having the lowest values, approximately less than half those of white subjects.

Conclusion White normotensive subjects in Cape Town have higher habitual intakes of sodium, but also higher calcium intakes than their black and mixed-ancestry counterparts. Dietary differences may contribute to ethnic-related differences in blood pressure.

Background QT interval prolongation can lead to torsades de pointes, a potentially fatal arrhythmia. Although research exists on the relationship between QT prolongation and clinical outcome, few studies have described risk factors for prolonged QT interval in the general population.

Methods The Third National Health and Nutrition Examination Survey (NHANES III) collected electrocardiogram interval data on 8561 subjects over 40 years of age and projected results to the US population. QT was corrected for heart rate using Fridericia's formula. Logistic regression analyses were performed to identify factors independently associated with prolonged QTc interval, defined as being in the upper 5% of the population QTc interval distribution. Analyses were conducted separately for women and men as a result of differences in the QT distribution between the sexes and also because of potential effect modification. Analytical variables included age, race/ethnicity, electrolyte measurements, body mass index, the recent use of QT-prolonging drugs and past medical histories of stroke, thyroid disease, hypertension, diabetes and myocardial infarction.

Results Age, female sex, hypocalcemia (men), hypokalemia (women), and a history of thyroid disease and myocardial infarction (men) were associated with a prolonged QTc interval. In addition, taking QT-prolonging medications in the past month was associated with more than a twofold increase in the odds of prolonged QTc interval in both men and women.

Conclusions Healthcare practitioners should be aware that a prolonged QTc interval is a potential indicator of cardiovascular risk, and should exercise caution in prescribing potentially QT-prolonging medications to certain patients.

Background Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial.

Design and methods The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46–64 years and free of prior stroke, examined in 1991–1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

Results At baseline the mean serum tHcy concentration was 10.9 μmol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23–6.24] for any stroke and 2.61 (95% CI: 1.02–6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (> 11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14–0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15–1.09), compared with men in the lowest third.

Conclusion Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.

Background Gender differences in presentation and management of acute coronary syndromes (ACS) are well established internationally. This study investigated differences in a national Irish sample.

Design Cross-sectional survey.

Methods All centres (n = 39) admitting cardiac patients to intensive/coronary care provided information on 25 consecutive acute myocardial infarction patients and other ACS patients admitted concurrently (n = 1365 episodes). Patient data was analyzed in terms of those with prior ACS/revascularization, and those without.

Results Men with prior established ACS/revascularization were twice as likely to have received revascularization procedures (coronary artery bypass graft or percutaneous coronary intervention) prior to admission when controlling for age, total cholesterol and insurance status [odds ratio (OR) 1.97, 95% confidence interval (CI) 1.18–3.29, P=0.011]. No gender differences were seen in acute-phase reperfusion (OR 0.96, 95% CI 0.76–1.24, P>0.05) or antiplatelet therapy (OR 0.99, 95% CI 0.69–1.41, P>0.05). For patients with prior ACS/revascularization, men were twice as likely to receive statins on discharge after adjustment for age and total cholesterol (OR 1.94, 95% CI 1.02–3.71, P=0.045).

Conclusions Women were treated differently to men. Fewer women with a positive history of ACS received revascularization prior to current admission and fewer women were prescribed lipid-lowering medications on discharge. Acute phase hospital treatment was not gender determined. These findings have implications for secondary prevention in Ireland.

Background Causes of variation in cardiovascular risk factors include biological variation within individuals, and more permanent differences between individuals, which are at least partly genetic in origin. We have compared the magnitude of genetic and non-genetic factors within and across occasions through repeated measures of plasma cholesterol in twin subjects, and have also determined how far the same genes affect cholesterol levels at different ages.

Methods Data on plasma total cholesterol were extracted for 208 twin pairs who had provided blood on up to six occasions across a period of 17 years. They were aged 18–30 years at the time of first study and 30–47 at the time of the last. Multivariate models of variation due to genetic, shared environmental and unique environmental factors were fitted to the multi-occasion data and the proportions of variation due to these factors were estimated.

Results One genetic factor influenced plasma cholesterol on all occasions and a second genetic factor only influenced cholesterol results on the fifth and sixth occasions 10–17 years after the first. Environmental factors did not have significant long-term effects.

Conclusions We conclude that individuals’ long-term mean plasma cholesterol values are strongly genetically determined, but that some of these genes are age-specific in their effects.

Background Cigarette smoking has declined whereas the use of smokeless tobacco is increasing. There is an ongoing debate as to whether smokeless tobacco is a recommendable strategy to help smokers to quit. However, very few studies have examined the association between smokeless tobacco, namely snuff, and coronary heart disease, which implies that it has not been possible to provide scientific results for public health policies and clinical guidelines concerning the use of smokeless tobacco.

Design A follow-up study.

Methods A random sample of 3120 healthy men aged 30–74 years was interviewed in 1988 and 1989 and followed up to the year 2000 with regard to coronary heart disease. Cox regression was used to estimate the relative risk of coronary heart disease in six categories of smoking and snuffing habits, after adjustment for established risk factors for coronary heart disease.

Results Smokers, former smokers, and those who combined smoking and snuffing had significantly higher hazard ratios than never-smokers. The very highest hazard ratio was found among individuals combining smoking and snuffing. Daily snuffers had a hazard ratio of 1.62 (95% confidence interval 0.70–3.03) after adjustment for age.

Conclusions Even though the association between daily snuffing and coronary heart disease was non-significant, the hazard ratio was markedly increased. Therefore, smokers should not use smokeless tobacco in order to quit smoking, especially as safer alternatives are available. Further studies in different settings are required to provide scientific results for public health policies and clinical guidelines.

Background Chronic heart failure (CHF) is accompanied by an inflammatory activation which occurs both systemically and in the skeletal muscle. Exercise training has been shown to reduce the local expression of cytokines and inducible nitric oxide synthase (iNOS) in muscle biopsies of CHF patients. INOS-derived NO can inhibit oxidative phosphorylation and contribute to skeletal muscle dysfunction in CHF.

Design To investigate the correlation between changes in local iNOS expression associated with regular exercise and changes in aerobic enzyme activities in the skeletal muscle of patients with CHF. Twenty male CHF patients [ejection fraction 25% (SE 2), age 54 (SE 2) years] were randomized to a training (n = 10) or a control group (C, n = 10).

Methods At baseline and after 6 months skeletal muscle iNOS expression was measured by real-time polymerase chain reaction. INOS protein and protein nitrosylation were assessed by immunohistochemistry. Cytochrome c oxidase (COX) activity was quantified electrochemically using the Clark oxygen electrode.

Results Exercise training led to a 27% increase in cytochrome c oxidase activity [from 21.8 (SE 3.2) to 27.7 (SE 3.5) nmol O₂/mg per min, P=0.02 versus baseline]. Changes in iNOS expression and iNOS protein content were inversely correlated with changes in COX-activity (r= −0.60, P=0.01; r= −0.71, P<0.001).

Conclusions The inverse correlation between iNOS expression/iNOS protein content and COX-activity indicates that local anti-inflammatory effects may contribute to improved muscular oxidative metabolism.

Background Chronic heart failure (CHF) is associated with progressive muscle atrophy and reduced local expression of insulin-like growth factor I (IGF-I).

Design The present study was designed to test the hypothesis that the local deficiency of IGF-I in the skeletal muscle of patients with CHF would respond to a 6-months aerobic training intervention. Therefore, 18 patients [mean age 52.4 (SD 4.8) years, left ventricular ejection function (LVEF) 27 (SD 6)%] were prospectively randomized to either 6 months of training or sedentary lifestyle.

Methods Serum levels of growth hormone (GH) were measured by immunofluorometric assay, IGF-I by competitive solid phase immunoassay. IGF-I expression was assessed in vastus lateralis biopsies by real-time PCR.

Results Exercise training led to a significant increase in peak oxygen uptake by 26% [from 20.3 (SD 3.3) ml/kg per min to 25.5 (SD 5.7) ml/kg per min, P=0.003 versus control]. Local expression of IGF-I increased significantly after exercise training by 81% [from 6.3 (SE 0.8) to 11.4 (SE 1.4) relative units, P=0.007 versus control] while IGF-I receptor expression was reduced by 33% [from 20.0 (SE 2.1) to 13.8 (SE 1.7) relative units, P=0.008 versus control]. Serum growth hormone (GH) rose modestly from 0.12 (SE 0.07) to 0.65 (SE 0.37) ng/ml in the training group (P=0.043 versus baseline), however, this change was not significant compared to the control group (P=0.848). IGF-I serum levels remained virtually unchanged.

Conclusions Exercise training improves local IGF-I expression without significant changes of systemic parameters of the GH/IGF-I axis. These findings indicate that exercise training has the therapeutic potential to attenuate peripheral skeletal muscle alterations in particular with respect to local IGF-I expression in patients with moderate CHF.

Background Increased numbers of circulating endothelial progenitor cells (EPC) are associated with improved vascular function. Exercise is a central component of the primary prevention of vascular diseases. The effect of physical activity on circulating EPC in healthy individuals is not known.

Design A prospective crossover study.

Methods and results In order to study a potential link between the extent of physical exercise and progenitor cells in humans, EPC were quantified by flow cytometry and cell culture in 25 healthy volunteers undergoing three protocols of running exercise. Intensive running, defined as 30 min at 100% of the velocity of the individual anaerobic threshold (IAT; ∼82% maximal oxygen consumption; VO₂max), as well as moderate running with 30 min at 80% of the velocity of the IAT (∼68% VO₂max), increased circulating EPC numbers to 235±93% and 263±106% of control levels, respectively. However, moderate short-term running for 10 min did not upregulate EPC counts. The maximum increase in circulating EPC numbers was observed 10–30 min after intensive running. Exercise increased EPC migratory and colony-forming capacity.

Conclusions Intensive and moderate exercising for 30 min, but not for 10 min, increased circulating levels of EPC, which may represent an important beneficial outcome of physical exercise. The data support the notion that increased numbers of EPC correlate with cardiovascular health and suggest EPC quantification as a novel surrogate parameter of the vascular effects of exercising.

In 927 biologically unrelated Caucasian patients with coronary artery disease it was investigated whether the NcoI restriction fragment length polymorphism of the muscle-specific creatine kinase (CKMM) gene is associated with aerobic power and with the response to physical training. Physical training significantly (P<0.001) increased peak oxygen consumption in the GG, AG and AA NcoI genotypes. Covariate-adjusted peak oxygen consumption at baseline, after training and the response to training were not different across CKMM NcoI genotypes.