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Background and purpose: Risk factors for stroke differ between women and men in general populations. However, little is known about sex differences in secondary prevention. We investigated if sex interacted with modifiable risk factors for stroke in a large arterial disease cohort. Methods: Within the prospective UCC-SMART study, 13,898 patients (35% women) with atherosclerotic disease or high-risk factor profile were followed up to 23 years for stroke incidence or recurrence. Hypertension, smoking, diabetes, overweight, dyslipidemia, high alcohol use, and physical inactivity were studied as risk factors. Association between these factors and ischemic and hemorrhagic stroke incidence or recurrence was studied in women and men using Cox proportional hazard models and Poisson regression models. Women-to-men relative hazard ratios (RHR) and rate differences (RD) were estimated for each risk factor. Left-truncated age was used as timescale. Results: The age-adjusted stroke incidence rate was lower in women than men (3.9 vs 4.4 per 1000 person-years), as was the age-adjusted stroke recurrence rate (10.0 vs 11.7). Hypertension and smoking were associated with stroke risk in both sexes. HDL cholesterol was associated with lower stroke incidence in women but not in men (RHR 0.49; CI 0.27–0.88; and RD 1.39; CI − 1.31 to 4.10). Overweight was associated with a lower stroke recurrence in women but not in men (RHR 0.42; CI 0.23–0.80; and RD 9.05; CI 2.78–15.32). Conclusions: In high-risk population, sex modifies the association of HDL cholesterol on stroke incidence, and the association of overweight on stroke recurrence. Our findings highlight the importance of sex-specific secondary prevention. [ABSTRACT FROM AUTHOR]

The purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28–4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59–0.72). Calibration for models II–V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59–29.39)) and model V (NRI 20.00% (95%CI 5.59–34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+. Addition of the TAC or heart valve score did not improve risk predictions. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess whether the association between angiotensin-converting enzyme (ACE) inhibitor use and the incidence of treated diabetes mellitus is modified by genetic polymorphisms in the renin-angiotensin system (RAS).In a nested case–control study, treated hypertensive patients were genotyped for ACE (insertion (I)/deletion (D)), angiotensinogen (AGT; M235T) and angiotensin II type 1 receptor (AGTR1; A1166C). Cases of newly treated diabetes were identified based on pharmacy records and controls were not yet drug treated for diabetes (case:control ratio 1:10). Self-administered questionnaires and physical examinations were used to assess risk factors for diabetes mellitus. Logistic regression was used to calculate the relative risk of diabetes associated with ACE inhibitor use relative to other antihypertensive treatment, stratified by the RAS genotypes. Among 205 cases and 2050 controls, homozygous 1166A carriers of the AGTR1 gene had a significantly decreased incidence of diabetes associated with current use of ACE inhibitors (odds ratio, OR: 0.47; 95% CI: 0.26–0.84), whereas this incidence was increased among 1166C allele carriers (OR: 1.32; 95% CI: 0.81–2.14). The interaction OR was 3.21 (95% CI: 1.53–6.75). ACE I allele carriers had a significantly reduced incidence of diabetes associated with ACE inhibitors use (OR: 0.63; 95% CI: 0.41–0.98), whereas DD homozygotes had no reduced risk (OR: 0.95; 95% CI: 0.46–1.96). The risk of diabetes associated with ACE inhibitor use was not significantly modified by the AGT-M235T polymorphism. Treatment with ACE inhibitors in hypertensive subjects significantly reduces the occurrence of diabetes in homozygous 1166A carriers of the AGTR1 gene and carriers of the ACE I allele, but not in 1166C allele carriers of the AGTR1 gene and in homozygous ACE D allele carriers.Journal of Human Hypertension (2008) 22, 774–780; doi:10.1038/jhh.2008.62; published online 19 June 2008 [ABSTRACT FROM AUTHOR]

Objective:Low B-vitamin status and high levels of serum homocysteine are found in depressed inpatients, but results of population-based studies of this association are inconclusive. We investigated whether a low dietary intake of B6-9-12 vitamins and high levels of serum homocysteine are associated with depressive symptoms in elderly men.Methods:The study sample included a total of 332 men aged 70–90 years who were free from cardiovascular diseases and diabetes at baseline in 1990. Depressive symptoms were measured with the Zung Self-rating Depression Scale at baseline in 1990 and dietary factors with the crosscheck dietary history method in 1985 and 1990. Serum levels of homocysteine were obtained in 1985. Multiple linear and logistic regression analyses were performed.Results:Dietary intake of folate (−1.19, 95% CI −2.03; −0.36) and vitamin B6 (−2.09, 95% CI −2.92; −1.26) per standard deviation increase was associated with lower levels of serum homocysteine, while vitamin B12 was not associated with serum homocysteine. Intake of folate, vitamin B6, vitamin B12 and levels of serum homocysteine were not related to depressive symptoms.Conclusions:Our results do not support the hypothesis that a low dietary intake of B6-9-12 vitamins and high levels of serum homocysteine are related to depression in healthy elderly men.European Journal of Clinical Nutrition (2008) 62, 939–945; doi:10.1038/sj.ejcn.1602804; published online 30 May 2007 [ABSTRACT FROM AUTHOR]