Summary Background Around 80% of all cardiovascular deaths occur in developing countries. Assessment of those patients at high risk is an important strategy for prevention. Since developing countries ...have limited resources for prevention strategies that require laboratory testing, we assessed if a risk prediction method that did not require any laboratory tests could be as accurate as one requiring laboratory information. Methods The National Health and Nutrition Examination Survey (NHANES) was a prospective cohort study of 14 407 US participants aged between 25–74 years at the time they were first examined (between 1971 and 1975). Our follow-up study population included participants with complete information on these surveys who did not report a history of cardiovascular disease (myocardial infarction, heart failure, stroke, angina) or cancer, yielding an analysis dataset N=6186. We compared how well either method could predict first-time fatal and non-fatal cardiovascular disease events in this cohort. For the laboratory-based model, which required blood testing, we used standard risk factors to assess risk of cardiovascular disease: age, systolic blood pressure, smoking status, total cholesterol, reported diabetes status, and current treatment for hypertension. For the non-laboratory-based model, we substituted body-mass index for cholesterol. Findings In the cohort of 6186, there were 1529 first-time cardiovascular events and 578 (38%) deaths due to cardiovascular disease over 21 years. In women, the laboratory-based model was useful for predicting events, with a c statistic of 0·829. The c statistic of the non-laboratory-based model was 0·831. In men, the results were similar (0·784 for the laboratory-based model and 0·783 for the non-laboratory-based model). Results were similar between the laboratory-based and non-laboratory-based models in both men and women when restricted to fatal events only. Interpretation A method that uses non-laboratory-based risk factors predicted cardiovascular events as accurately as one that relied on laboratory-based values. This approach could simplify risk assessment in situations where laboratory testing is inconvenient or unavailable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Galectin-3 is an emerging biomarker of myocardial fibrosis, inflammation, and immune response. We sought to examine the relation of plasma galectin-3 with cardiovascular (CVD) mortality, ...all-cause mortality and incident heart failure. We performed a literature search for all relevant publications using Ovid MEDLINE, Google Scholar and other databases up to January 2016. Two reviewers independently extracted data and assessed risk of bias. We extracted hazard ratios from regression models that adjusted for age, sex, race, body mass index, smoking, hypertension, hyperlipidemia, diabetes, natriuretic peptides, and renal function, when available. A total of 18 studies with 32,350 participants (323,090 person-years of follow-up) met criteria for analysis. The mean age was 57.3 years and 47.2% of participants were women, with a follow-up duration median of 5 years, IQR: 2.9-10 years. Of the 18 studies, 13 (72%) adjusted for NT-proBNP and renal function in the multivariable adjusted models. Using a random effects meta-analysis, we found a HR of 1.10 (95% CI: 1.05-1.14) for all-cause mortality, 1.22 (95% CI: 1.05-1.39) for CVD mortality, and 1.12 (95% CI: 1.04-1.21) for heart failure risk for each one standard deviation increase in galectin-3 level. In a subgroup analysis of CVD mortality, the HR was 1.44 (1.09-1.79) for patients with heart failure, and 1.09 (0.91-1.27) for the general population. In conclusion, our results suggest that elevated plasma galectin-3 is associated with a higher risk of all-cause mortality, CVD mortality and heart failure. It may add prognostic value beyond that provided by traditional CVD risk factors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Limited data suggest that athletes may have a higher risk of developing atrial fibrillation (AF); however, there has been no large prospective assessment of the relation between vigorous exercise and ...AF. Logistic regression analyses stratified by time were used to assess the association between frequency of vigorous exercise and risk of developing AF in 16,921 apparently healthy men in the Physicians' Health Study. During 12 years of follow-up, 1,661 men reported developing AF. With increasing frequency of vigorous exercise (0, 1, 1 to 2, 3 to 4, 5 to 7 days/week), multivariate relative risks for the full cohort were 1.0 (referent), 0.90, 1.09, 1.04, and 1.20 (p = 0.04). This risk was not significantly increased when exercise habits were updated or in models excluding variables that may be in the biological pathway through which exercise influences AF risk. In subgroup analyses, this increased risk was observed only in men <50 years of age (1.0, 0.94, 1.20, 1.05, 1.74, p <0.01) and joggers (1.0, 0.91, 1.03, 1.30, 1.53, p <0.01), where risks remained increased in all analyses. In conclusion, frequency of vigorous exercise was associated with an increased risk of developing AF in young men and joggers. This risk decreased as the population aged and was offset by known beneficial effects of vigorous exercise on other AF risk factors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Background Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about possible cancer risks. We aimed to assess any ...effects on site-specific cancer rates in the randomised trials of folic acid supplementation, at doses higher than those from fortification. Methods In these meta-analyses, we sought all trials completed before 2011 that compared folic acid versus placebo, had scheduled treatment duration at least 1 year, included at least 500 participants, and recorded data on cancer incidence. We obtained individual participant datasets that included 49 621 participants in all 13 such trials (ten trials of folic acid for prevention of cardiovascular disease n=46 969 and three trials in patients with colorectal adenoma n=2652). All these trials were evenly randomised. The main outcome was incident cancer (ignoring non-melanoma skin cancer) during the scheduled treatment period (among participants who were still free of cancer). We compared those allocated folic acid with those allocated placebo, and used log-rank analyses to calculate the cancer incidence rate ratio (RR). Findings During a weighted average scheduled treatment duration of 5·2 years, allocation to folic acid quadrupled plasma concentrations of folic acid (57·3 nmol/L for the folic acid groups vs 13·5 nmol/L for the placebo groups), but had no significant effect on overall cancer incidence (1904 cancers in the folic acid groups vs 1809 cancers in the placebo groups, RR 1·06, 95% CI 0·99–1·13, p=0·10). There was no trend towards greater effect with longer treatment. There was no significant heterogeneity between the results of the 13 individual trials (p=0·23), or between the two overall results in the cadiovascular prevention trials and the adenoma trials (p=0·13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast, or any other specific site. Interpretation Folic acid supplementation does not substantially increase or decrease incidence of site-specific cancer during the first 5 years of treatment. Fortification of flour and other cereal products involves doses of folic acid that are, on average, an order of magnitude smaller than the doses used in these trials. Funding British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Background Excess body-mass index (BMI) has been associated with adverse outcomes in prostate cancer, and hyperinsulinaemia is a candidate mediator, but prospective data are sparse. We ...assessed the effect of prediagnostic BMI and plasma C-peptide concentration (reflecting insulin secretion) on prostate cancer-specific mortality after diagnosis. Methods This study involved men diagnosed with prostate cancer during the 24 years of follow-up in the Physicians' Health Study. BMI measurements were available at baseline in 1982 and eight years later in 1990 for 2546 men who developed prostate cancer. Baseline C-peptide concentration was available in 827 men. We used Cox proportional hazards regression models controlling for age, smoking, time between BMI measurement and prostate cancer diagnosis, and competing causes of death to assess the risk of prostate cancer-specific mortality according to BMI and C-peptide concentration. Findings Of the 2546 men diagnosed with prostate cancer during the follow-up period, 989 (38·8%) were overweight (BMI 25·0–29·9 kg/m2 ) and 87 (3·4%) were obese (BMI ≥30 kg/m2 ). 281 men (11%) died from prostate cancer during this follow-up period. Compared with men of a healthy weight (BMI <25 kg/m2 ) at baseline, overweight men and obese men had a significantly higher risk of prostate cancer mortality (proportional hazard ratio HR 1·47 95% CI 1·16–1·88 for overweight men and 2·66 1·62–4·39 for obese men; ptrend <0·0001). The trend remained significant after controlling for clinical stage and Gleason grade and was stronger for prostate cancer diagnosed during the PSA screening era (1991–2007) compared with during the pre-PSA screening era (1982–1990) or when using BMI measurements obtained in 1990 compared with those obtained in 1982. Of the 827 men with data available for baseline C-peptide concentration, 117 (14%) died from prostate cancer. Men with C-peptide concentrations in the highest quartile (high) versus the lowest quartile (low) had a higher risk of prostate cancer mortality (HR 2·38 95% CI 1·31–4·30; ptrend =0·008). Compared with men with a BMI less than 25 kg/m2 and low C-peptide concentrations, those with a BMI of 25 kg/m2 or more and high C-peptide concentrations had a four-times higher risk of mortality (4·12 1·97–8·61; pinteraction =0·001) independent of clinical predictors. Interpretation Excess bodyweight and a high plasma concentration of C-peptide both predispose men with a subsequent diagnosis of prostate cancer to an increased likelihood of dying of their disease. Patients with both factors have the worst outcome. Further studies are now needed to confirm these findings. Funding The National Institutes of Health research grants CA42182, CA90598, CA58684, CA34944, CA40360, HL26490, HL34595, the National Cancer Institute of Canada, and the Prostate Cancer Foundation, Santa Monica, CA, USA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Measures of Obesity and Cardiovascular Risk Among Men and Women Rebecca P. Gelber, J. Michael Gaziano, E. John Orav, JoAnn E. Manson, Julie E. Buring, Tobias Kurth Controversy exists regarding the ...optimal approach to measure adiposity. Using data from 2 large prospective cohorts (the Physicians' Health Study and Women's Health Study), we examined associations between various anthropometric indexes (body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio WHtR) and the risk of developing cardiovascular disease (CVD). While the WHtR demonstrated statistically the best model fit and strongest associations with CVD among both men and women, differences in cardiovascular risk assessment using other indexes were small and likely not clinically consequential. Our findings emphasize that higher levels of adiposity, however measured, confer an increased risk of CVD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background The prevalence of vascular risk factors, cardiovascular disease, and restless legs syndrome increases with age. Prior studies analyzing the associations between vascular risk ...factors, cardiovascular disease, and restless legs syndrome found controversial results. We therefore aim to evaluate the associations between prevalent vascular risk factors, prevalent cardiovascular disease, and restless legs syndrome. Methods We conducted a cross-sectional study among 22,786 participants of the US Physicians' Health Studies I and II. Restless legs syndrome was classified according to the 4 minimal diagnostic criteria. Vascular risk factors and restless legs syndrome symptoms were self-reported. Prevalent cardiovascular disease events, including major cardiovascular disease, stroke, and myocardial infarction, were confirmed by medical record review. Age- and multivariable-adjusted logistic regression models were used to evaluate the association among vascular risk factors, prevalent cardiovascular disease events, and restless legs syndrome. Results The mean age of the cohort was 67.8 years. The prevalence of restless legs syndrome was 7.5% and increased significantly with age. Diabetes significantly increased the odds of restless legs syndrome (odds ratio OR, 1.41; 95% confidence interval CI, 1.21-1.65), whereas frequent exercise (OR, 0.78; 95% CI, 0.67-0.91) and alcohol consumption of 1 or more drinks per day (OR, 0.80; 95% CI, 0.69-0.92) significantly reduced the odds of restless legs syndrome in multivariable-adjusted models. Prevalent stroke showed an increased multivariable-adjusted OR of 1.40 (1.05-1.86), whereas men with prevalent myocardial infarction had a decreased OR of 0.73 (0.55-0.97) for restless legs syndrome. Conclusions The restless legs syndrome prevalence among US male physicians is similar to that of men of the same age group in other western countries. A history of diabetes is the most consistent risk factor associated with restless legs syndrome. Prevalent stroke and myocardial infarction are related to restless legs syndrome prevalence.
A Prospective Study of Cigarette Smoking and Risk of Incident Hypertension in Women Thomas S. Bowman, J. Michael Gaziano, Julie E. Buring, Howard D. Sesso Few prospective studies have examined the ...relationship between smoking and hypertension. In a prospective cohort study among 28,236 women in the Women’s Health Study, there were 8,571 (30.4%) cases of incident hypertension during a median follow-up of 9.8 years. The multivariable-adjusted hazard ratios of developing hypertension among never, former, and current smokers of 1 to 14 and ≥15 cigarettes per day were 1.00 (reference), 1.03 (95% confidence interval CI 0.98 to 1.08), 1.02 (95% CI 0.92 to 1.13), and 1.11 (95% CI 1.03 to 1.21), respectively. In conclusion, cigarette smoking was modestly associated with an increased risk of developing hypertension, with an effect that was strongest among women smoking at least 15 cigarettes per day.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Comparative effectiveness research (CER) may be defined informally as an assessment of available options for treating specific medical conditions in selected groups of patients. In this ...context, the most prominent features of CER are the various patient populations, medical ailments, and treatment options involved in any particular project. Yet, each research investigation also has a corresponding study design or “architecture,” and in patient-oriented research a common distinction used to describe such designs are randomized controlled trials (RCTs) versus observational studies. The purposes of this overview, with regard to CER, are to (1) understand how observational studies can provide accurate results, comparable to RCTs; (2) recognize strategies used in selected newer methods for conducting observational studies; (3) review selected observational studies from the Veterans Health Administration; and (4) appreciate the importance of fundamental methodological principles when conducting or evaluating individual studies.
Abstract Background Previous studies evaluating the association of cardiovascular disease and vascular risk factors with restless legs syndrome showed inconsistent results, especially for the ...potential relation between various vascular risk factors and restless legs syndrome. We therefore aimed to analyze the relationships between vascular risk factors, prevalent cardiovascular disease, and restless legs syndrome. Methods This is a cross-sectional study of 30,262 female health professionals participating in the Women's Health Study (WHS). Restless legs syndrome was defined according to diagnostic criteria of the International Restless Legs Study Group. Information on vascular risk factors (diabetes, hypertension, hypercholesterolemia, body mass index BMI, alcohol, smoking, exercise, and family history of myocardial infarction) was self-reported. Cardiovascular disease events (coronary revascularization, myocardial infarction, and stroke) were confirmed by medical record review. Prevalent major cardiovascular disease was defined as nonfatal stroke or nonfatal myocardial infarction. Logistic regression models were used to evaluate the association between vascular risk factors, prevalent cardiovascular disease, and restless legs syndrome. Results Of the 30,262 participants (mean age: 63.6 years), 3624 (12.0%) reported restless legs syndrome. In multivariable-adjusted models, BMI (odds ratio OR for BMI ≥ 35 kg/m2 , 1.35; 95% confidence interval CI, 1.17-1.56), diabetes (OR, 1.19; 95% CI, 1.04-1.35), hypercholesterolemia (OR, 1.17; 95% CI, 1.09-1.26), smoking status (OR for ≥ 15 cigarettes/day, 1.41; 95% CI, 1.19-1.66), and exercise (OR for exercise ≥ 4 times/week, 0.84; 95% CI, 0.74-0.95) were associated with restless legs syndrome prevalence. We found no association between prevalent cardiovascular disease (major cardiovascular disease, myocardial infarction, and stroke) and restless legs syndrome prevalence. Women who underwent coronary revascularization had a multivariable-adjusted OR of 1.39 (1.10-1.77) for restless legs syndrome. Conclusions In this large cohort of female health professionals, various vascular risk factors are associated with the prevalence of restless legs syndrome. We could not confirm the results of previous reports indicating an association between prevalent cardiovascular disease and restless legs syndrome.
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