Is early life body weight a predictor of longevity and tumor risk in rats?

Heavy body weight (BW) is thought to be associated with reduced longevity and age-associated diseases, including cancer, both in laboratory rodents and humans. To further investigate the interactions between BW, longevity and spontaneous tumor development, we measured the correlations between BW in early life, BW in middle life, and parameters of life span and tumorigenesis in male and female outbred rats. The data show that BW at the ages of both 3 and 12 months are significant predictors of longevity in rats. Heavier female rats tend to live longer than the lighter female rats, while in male those who were light at 3 months but heavy at 12 month had the best longevity. BW at the age 3 months was not predictive of tumor growth but being heavier at the age of 1 year did confer an increased risk of tumor development for both male and female rats.     

Is the relationship of body mass index to severity of coronary artery disease different from that of waist-to- hip ratio and severity of coronary artery disease? Paradoxical findings

Although obesity has been regarded as an independent risk factor for coronary artery disease (CAD) by the American Heart Association (AHA) and investigators of the Framingham Heart study in the 1980s and 1990s,1-3 this has not been supported by recent clinical trials. Moreover, the positive linear relationships between obesity and CAD, as reported by some studies, were as a result of univariate analysis of their data. However, by using multivariate analysis of these study data, which included other cardiovascular risk factors such as diabetes mellitus (DM), hypertension (HTN) and hyperlipidaemia, this relationship was shown to be dramatically reduced.4,5In the Munster Heart study (PROCAM) and similar studies, the positive relationship between body mass index (BMI) and cardiovascular risk factors, with cardiac mortality, which attributed obesity as an independent risk factor, appeared to be due to the associated cardiovascular risk factors that usually accompany obesity.6-10 In these studies there was also a strong positive correlation between high BMI and other cardiovascular risk factors.However, findings of recent studies in this regard were opposite to those of previous studies. According to their findings, not only was obesity not a risk factor for CAD but it also had a protective effect on the progression of CAD, which is known as the ‘obesity paradox’.11,12 On the other hand, abdominal adiposity has always been associated with increased cardiovascular disease and mortality rate, independent of patients’ weight.13,14This study was designed to evaluate not only the impact of BMI but also waist-to-hip ratio (WHR) on the severity of CAD, based on angiographic findings.     

Is serum uric acid a risk factor for coronary heart disease?

The role of uric acid as an independent risk factor in the development of coronary heart disease (CHD) has been questioned as serum urate is related to many of the established etiological risk factors for cardiovascular disease which could confound the observed association. This review assesses the role of elevated serum uric acid as an independent role for coronary heart disease.     

Do coronary heart disease risk factors change over time?

The stability over a 12-year period of several coronary heart disease (CHD) risk factors was evaluated in 348 individuals who had remained healthy following baseline measurements made of the same variables in 1981. CHD risk factors evaluated were fasting and post-glucose challenge (120-minute) plasma glucose and insulin concentrations, plasma triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) concentrations, and the ratio of LDL/HDL cholesterol concentrations. Approximately 40% to 60% of individuals in the highest CHD risk quartile (or lowest in the case of HDL cholesterol concentrations) in 1981 were still at highest risk in 1993. A similar proportion of individuals at lowest risk in 1981 were still in that category in 1993. At least 50% of the participants in this prospective analysis experienced a change by 1 quartile or more in each of the metabolic CHD risk factors measured, and these differences were highly statistically significant for all variables measured with the exception of the TG and HDL cholesterol concentrations. These results demonstrate that the implicit assumption in epidemiological studies that CHD risk factors at baseline remain stable may require examination.     

Is the apoE4 allele an independent predictor of coronary events?

PURPOSE: Although the apolipoprotein E genotype epsilon4 (apoE4) has been associated with high cholesterol levels, whether it is an independent predictor of coronary events is not certain. SUBJECTS AND METHODS: We measured apoE genotypes in 730 participants in the Baltimore Longitudinal Study of Aging (421 men and 309 women, mean [+/- SD] age of 52+/-17 years) who were free of preexisting coronary heart disease. A proportional hazards regression model was used to study the association between risk factors and the occurrence of coronary events, defined as angina pectoris, documented myocardial infarction by history or major Q waves on the electrocardiogram (Minnesota Code 1:1 or 1:2), or coronary death, adjusted for other risk factors, including total plasma cholesterol level. RESULTS: The apoE4 allele was observed in 200 subjects (27%), including 183 heterozygotes and 17 homozygotes. Coronary risk factor profiles were similar in those with and without apoE4. Coronary events developed in 104 (14%) of the 730 subjects, including 77 (18%) of the 421 men during a mean follow-up of 20 years and 27 (9%) of the 309 women during a mean follow-up of 13 years. Coronary events occurred significantly more frequently in subjects with apoE4 (n = 40, 20%) than in those without this allele (64, 12%, P <0.05). In a multivariate model, apoE4 was an independent predictor of coronary events in men (risk ratio [RR]= 2.9, 95% confidence interval [CI]: 1.8 to 4.5, P<0.0001) but not in women (RR = 0.9, 95% CI: 0.4 to 1.9, P = 0.62). CONCLUSION: The apoE4 genotype is a strong independent risk factor for coronary events in men, but not women. The association does not appear to be mediated by differences in total cholesterol levels.     

Hyperhomocystinemia: a risk factor or a consequence of coronary heart disease?

BACKGROUND: Mild hyperhomocystinemia has been suggested as an indicator of an increased risk of cardiovascular disease. OBJECTIVE: To examine whether serum homocysteine concentration is a predictor of coronary heart disease (CHD) events. METHODS: A case-control study, nested in a population-based cohort study was used. During a follow-up of 13 years, 166 major coronary events (death from CHD or nonfatal myocardial infarction) occurred in men with evidence of heart disease at baseline and 272 events in men without a history of heart disease. Two controls per case were selected by individual matching. RESULTS: Among men with known heart disease at baseline, the relative risk (95% confidence interval) of CHD events adjusted for age, smoking, hypertension, diabetes mellitus, serum cholesterol level, body mass index, and alcohol consumption was 2.23 (95% confidence interval, 1.03-4.85) in the highest serum homocysteine quintile compared with the lowest quintile. Among the men free of heart disease at baseline, the corresponding relative risk was 0.90 (95% confidence interval, 0.51-1.60). CONCLUSIONS: This prospective study does not support the hypothesis that a high concentration of serum homocysteine is a risk factor for coronary events in a population free of heart disease. However, it does suggest that mild hyperhomocystinemia predicts secondary coronary events in men with heart disease, possibly as a consequence of atherosclerotic changes.     

Is Helicobacter pylori infection a risk factor for disease severity in systemic sclerosis?

Helicobacter pylori (H. pylori) is suspected to be one of the factors triggering systemic sclerosis (SSc). Data on the possible role of H. pylori are lacking. The aim of this study was to assess the effect of H. pylori infection in SSc patients. Forty-two SSc patients without dyspeptic symptoms were recruited—26 were H. pylori-positive and 16 were H. pylori-negative on the basis of invasive test. We evaluated the disease severity using clinical and laboratory parameters according to the Medsger Severity Scale. The level of SSc activity was evaluated according to Valentini activity score. The prevalence of H. pylori infection in population of SSc patients is 62 %. Severity of skin, gastrointestinal, and joint/tendon involvement was different between H. pylori-positive and -negative SSc patients (p < 0.001 for skin involvement, p = 0.002 and p = 0.03 for gastrointestinal and joint/tendon involvement, respectively) as well as erythrocyte sedimentation rate (p = 0.002). Severity score according to Medsger was higher in the H. pylori-positive than in the H. pylori-negative SSc patients (p < 0.001). Our data suggest that H. pylori infection correlates with severity of skin, gastrointestinal, and joint/tendon involvement in SSc patients. H. pylori-positive SSc patients showed higher severity score compared to H. pylori-negative. Therefore, H. pylori infection may play a role in the pathogenesis of SSc and also can provide some prognostic information.     

Population-attributable risk of coronary heart disease risk factors during long-term follow-up: the Malmö Preventive Project

AIMS: To calculate the population-attributable risk (PAR) of coronary events (CE) from 10 risk factors, during long-term follow-up. METHODS: We used both case-cohort and case-control analyses for calculation of PAR in relation to 10 baseline risk factors. First CE (fatal or nonfatal, n=3072) in 22,444 males and 10,902 females was recorded during a mean follow-up of 20 years by use of national registers. RESULTS: Using a Cox regression analysis in a case-cohort design, smoking (prevalence in men 49%, women 37%) was the strongest risk factor, RR 2.29 (95% CI 2.09-2.52; PAR 39%), followed by hypercholesterolaemia, RR 1.70 (95% CI 1.56-1.86; PAR 18%), and diabetes, RR 1.67 (95% CI 1.41-1.99; PAR 3%). For women the strongest risk factors were smoking, RR 3.16 (95% CI 2.50-3.98; PAR 44%), diabetes, RR 2.59 (95% CI 1.78-3.76; PAR 6%), and hypertension, RR 2.47 (95% CI 1.94-3.14; PAR 23%). In men, smoking was the strongest predictor both after 10 years [RR 2.69 (95% CI 2.23-3.24)] and 20 years [RR 2.45 (95% CI 2.15-2.79)], followed by hypercholesterolaemia (RR 2.16-1.63), hypertension (RR 2.04-1.51), and diabetes (RR 1.85 -1.47). The case-control design gave very similar results. Total PAR varied from 74% (fully adjusted Cox regression, case-control, in men) to 116% in women (case-cohort). CONCLUSION: Smoking is the most important long-term risk factor for CE in both genders, based on data from a population with a high proportion of smokers. Ten measured variables explained almost all variation in risk and could be used as a basis for intervention programmes.     

Is there a 'window of opportunity' for intervention to reduce risk of coronary artery disease in SLE?

Patients with systemic lupus erythematosus (SLE) have a substantially enhanced risk for cardiovascular complications, especially coronary artery disease (CAD). Evidence from a recent study by Urowitz et al. indicates that the incidence not only of classic CAD risk factors but also of nontraditional CAD risk factors increases within the first 3 years after onset of SLE. The data indicate that patients with SLE require careful management of hypertension and hypercholesterolemia, smoking cessation, and increased physical activity in order to reduce the risk of CAD. Intensive immune intervention is likely to be related to reduction of risk from nontraditional CAD risk factors, but it is not known if this treatment approach also affects classic CAD risk factors. Although established in patients with rheumatoid arthritis in recent years, the effect of immune intervention on classic risk factors for CAD needs to be evaluated in patients with SLE, through either clinical studies or international registries.     

Is alcohol anti-inflammatory in the context of coronary heart disease?

Although the cardioprotective effect of alcohol has been primarily explained by its effect on blood lipids and platelets, could an anti-inflammatory mechanism be involved?