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Purpose: Cardiometabolic multimorbidity (CMM) is a major public health challenge. This study investigated the prospective relationships between diet quality, dietary components, and risk of CMM in older British men., Methods: We used data from the British Regional Heart Study of 2873 men aged 60-79 free of myocardial infarction (MI), stroke, and type 2 diabetes (T2D) at baseline. CMM was defined as the coexistence of two or more cardiometabolic diseases, including MI, stroke, and T2D. Sourcing baseline food frequency questionnaire, the Elderly Dietary Index (EDI), which was a diet quality score based on Mediterranean diet and MyPyramid for Older Adults, was generated. Cox proportional hazards regression and multi-state model were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: During a median follow-up of 19.3 years, 891 participants developed first cardiometabolic disease (FCMD), and 109 developed CMM. Cox regression analyses found no significant association between baseline EDI and risk of CMM. However, fish/seafood consumption, a dietary component of the EDI score, was inversely associated with risk of CMM, with HR 0.44 (95% CI 0.26, 0.73) for consuming fish/seafood 1-2 days/week compared to less than 1 day/week after adjustment. Further analyses with multi-state model showed that fish/seafood consumption played a protective role in the transition from FCMD to CMM., Conclusions: Our study did not find a significant association of baseline EDI with CMM but showed that consuming more fish/seafood per week was associated with a lower risk of transition from FCMD to CMM in older British men., (© 2023. The Author(s).)

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke., Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank., Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min -1 ·1.73 m -2 , compared with those with eGFR between 60 and 105 mL·min -1 ·1.73 m -2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min -1 ·1.73 m -2 , with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min -1 ·1.73 m -2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min -1 ·1.73 m -2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD., Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Aims: Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke., Methods: Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure., Results: The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke., Conclusions: Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

Background We aimed at investigating the association of circulating fatty acids with coronary heart disease (CHD) and stroke risk. Methods and Results We conducted an individual-participant data meta-analysis of 5 UK-based cohorts and 1 matched case-control study. Fatty acids (ie, omega-3 docosahexaenoic acid, omega-6 linoleic acid, monounsaturated and saturated fatty acids) were measured at baseline using an automated high-throughput serum nuclear magnetic resonance metabolomics platform. Data from 3022 incident CHD cases (13 104 controls) and 1606 incident stroke cases (13 369 controls) were included. Logistic regression was used to model the relation between fatty acids and odds of CHD and stroke, adjusting for demographic and lifestyle variables only (ie, minimally adjusted model) or with further adjustment for other fatty acids (ie, fully adjusted model). Although circulating docosahexaenoic acid, but not linoleic acid, was related to lower CHD risk in the fully adjusted model (odds ratio, 0.85; 95% CI, 0.76-0.95 per standard unit of docosahexaenoic acid), there was evidence of high between-study heterogeneity and effect modification by study design. Stroke risk was consistently lower with increasing circulating linoleic acid (odds ratio for fully adjusted model, 0.82; 95% CI, 0.75-0.90). Circulating monounsaturated fatty acids were associated with higher CHD risk across all models and with stroke risk in the fully adjusted model (odds ratio, 1.22; 95% CI, 1.03-1.44). Saturated fatty acids were not related to increased CHD risk in the fully adjusted model (odds ratio, 0.94; 95% CI, 0.82-1.09), or stroke risk. Conclusions We found consistent evidence that linoleic acid was associated with decreased risk of stroke and that monounsaturated fatty acids were associated with increased risk of CHD. The different pattern between CHD and stroke in terms of fatty acids risk profile suggests future studies should be cautious about using composite events. Different study designs are needed to assess which, if any, of the associations observed is causal.

Aims/hypothesis: This study aimed to examine the association between copeptin (a surrogate marker of arginine vasopressin) and incident stroke, CHD and cardiovascular mortality in older men with and without diabetes., Methods: We conducted a prospective study of 3536 men aged 60-79 years who were followed for an average of 13 years. During this period, there were 437 major CHD events (fatal and non-fatal myocardial infarction [MI]), 323 stroke events (fatal and non-fatal) and 497 cardiovascular disease (CVD) deaths. Prevalent diabetes was defined on the basis of a history of doctor-diagnosed diabetes or fasting blood glucose ≥7.0 mmol or HbA1c ≥6.5% (48 mmol/mol) (n = 428)., Results: No association was seen between copeptin and incident stroke or CVD mortality in men without diabetes after adjustment for conventional cardiovascular risk factors, renal dysfunction, and insulin and N-terminal pro B-type natriuretic peptide levels. In contrast, elevated copeptin levels were associated with an increased risk of stroke and CVD mortality in men with diabetes after these adjustments. Compared with those in the lowest tertile of copeptin, men in the top tertile had adjusted relative HRs for stroke and CVD death of 2.34 (95% CI 1.04, 5.27) and 2.21 (1.12, 4.36), respectively. The risk of stroke and CVD mortality remained increased after the exclusion of men with prevalent stroke or MI. Higher levels of copeptin were associated with increased risk of CHD in the diabetic and non-diabetic groups, but these associations were attenuated after exclusion of individuals with a previous stroke or MI., Conclusions/interpretation: Copeptin was independently associated with an increased risk of incident stroke and CVD mortality in men with diabetes, but not in men without diabetes. Targeting the arginine vasopressin system might have beneficial effects on CVD mortality and stroke risk in older men with diabetes.

Objectives: Adiposity in middle age is an established risk factor for cardiovascular disease and type 2 diabetes; less is known about the impact of adiposity from early adult life. We examined the effects of high body mass index (BMI) in early and middle adulthood on myocardial infarction (MI), stroke and diabetes risks., Design: A prospective cohort study., Participants: 7735 men with BMI measured in middle age (40-59 years) and BMI ascertained at 21 years from military records or participant recall., Primary and Secondary Outcome Measures: 30-year follow-up data for type 2 diabetes, MI and stroke incidence; Cox proportional hazards models were used to examine the effect of BMI at both ages on these outcomes, adjusted for age and smoking status., Results: Among 4846 (63%) men (with complete data), a 1 kg/m(2) higher BMI at 21 years was associated with a 6% (95% CI 4% to 9%) higher type 2 diabetes risk, compared with a 21% (95% CI 18% to 24%) higher diabetes risk for a 1 kg/m(2) higher BMI in middle age (hazard ratio (HR) 1.21, 95% CI 1.18 to 1.24). Higher BMI in middle age was associated with a 6% (95% CI 4% to 8%) increase in MI and a 4% (95% CI 1% to 7%) increase in stroke; BMI at 21 years showed no associations with MI or stroke risk., Conclusions: Higher BMI at 21 years of age is associated with later diabetes incidence but not MI or stroke, while higher BMI in middle age is strongly associated with all outcomes. Early obesity prevention may reduce later type 2 diabetes risk, more than MI and stroke., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease., Design: Mendelian randomisation meta-analysis of 56 epidemiological studies., Participants: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers., Main Outcome Measures: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption., Results: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95))., Conclusions: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health., (© Holmes et al 2014.)

Background and Purpose: Older adults have the highest risks of stroke and the lowest physical activity levels. It is important to quantify how walking (the predominant form of physical activity in older age) is associated with stroke., Methods: A total of 4252 men from a UK population-based cohort reported usual physical activity (regular walking, cycling, recreational activity, and sport) in 1998 to 2000. Nurses took fasting blood samples and made anthropometric measurements., Results: Among 3435 ambulatory men free from cardiovascular disease and heart failure in 1998 to 2000, 195 first strokes occurred during 11-year follow-up. Men walked a median of 7 (interquartile range, 3-12) hours/wk; walking more hours was associated with lower heart rate, D-dimer, and higher forced expiratory volume in 1 second. Compared with men walking 0 to 3 hours/wk, men walking 4 to 7, 8 to 14, 15 to 21, and >22 hours had age- and region-adjusted hazard ratios (95% confidence intervals) for stroke of 0.89 (0.60-1.31), 0.63 (0.40-1.00), 0.68 (0.35-1.32), and 0.36 (0.14-0.91), respectively, P (trend)=0.006. Hazard ratios were somewhat attenuated by adjustment for established and novel risk markers (inflammatory and hemostatic markers and cardiac function [N-terminal pro-brain natriuretic peptide]) and walking pace, but linear trends remained. There was little evidence for a dose-response relationship between walking pace and stroke; comparing average pace or faster to a baseline of slow pace, the hazard ratio for stroke was 0.65 (95% confidence interval, 0.44-0.97), which was fully mediated by time spent walking., Conclusions: Time spent walking was associated with reduced risk of onset of stroke in dose-response fashion, independent of walking pace. Walking could form an important part of stroke-prevention strategies in older people.

Background and Purpose: The association between adiposity and adipocytes and risk of stroke in older adults is uncertain. We have examined the association between adiposity measures and adipocytes (adiponectin and leptin) with incident stroke events in older men., Methods: Prospective study of 3411 men aged 60 to 79 years with no previous diagnosis of myocardial infarction, heart failure, or stroke followed-up for an average of 9 years, during which there were 192 incident major stroke events., Results: In age-adjusted analyses, body mass index and waist circumference were not significantly associated with risk of stroke in older men, although obese men (body mass index >30 kg/m(2)) showed the lowest risk of stroke. Despite the strong positive correlation between leptin and body mass index and waist circumference, risk of stroke was significantly increased in those in the top quartile of the leptin distribution. The increased risk remained after adjustment for potential confounders, including systolic blood pressure (adjusted hazard ratios top quartile versus bottom quartile: 2.03; confidence interval, 1.27-3.27]). Further adjustment for markers of inflammation (c-reactive protein), endothelial dysfunction (von Willebrand factor), fibrinolytic activity (d-dimer), and γ-glutamyl transferase attenuated the increased risk, but risk remained significantly increased (adjusted hazard ratios, 1.73; confidence interval, 1.06-2.83]). By contrast, no association was seen between adiponectin and risk of stroke., Conclusions: Conventional adiposity measures were not associated with increased stroke risk in older men. However, leptin (a good marker of percent fat mass), but not adiponectin, predicted stroke, suggesting a link between fat mass and stroke risk.

Background and Purpose: Abnormalities in blood coagulation and the fibrinolytic system have been associated with increased risk of stroke, but few prospective studies have studied the associations in older adults. We have examined the associations between fibrin D-dimer, tissue-type plasminogen activator, and von Willebrand factor (vWF) and risk of stroke in older men and examined their predictive roles separately in normotensive and hypertensive men., Methods: Prospective study of 3358 men aged 60 to 79 years with no previous diagnosis of myocardial infarction or stroke and without atrial fibrillation followed-up for an average of 9 years, during which there were 187 incident stroke events., Results: Increased levels of D-dimer and vWF were associated with significantly increased risk of major stroke events after adjustment for potential confounders, including systolic blood pressure (adjusted hazard ratios and 95% confidence interval per standard deviation increase in D-dimer and vWF were 1.24 [95% confidence interval, 1.08-1.44] and 1.25 [95% confidence interval, 1.09-1.45], respectively). No associations were seen with tPA after adjustment. The positive associations between D-dimer and vWF and incident stroke remained after additional adjustment for markers of inflammation (C-reactive protein, IL-6). D-dimer was associated with stroke in both normotensive and hypertensive men; vWF showed stronger associations in normotensive than in hypertensive men (test for interaction: P=0.52 for D-dimer; P<0.01 for vWF)., Conclusions: Fibrin D-dimer and vWF are associated with increased risk of stroke in older men. These associations were not explained by their associations with inflammation. D-dimer may be a useful marker to identify those at high risk for stroke among hypertensive men.

Background: CD40 ligand(CD40L) is implicated in atherosclerotic plaque formation., Objectives: We investigated prospective associations between circulating soluble CD40L and myocardial infraction (MI) or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors., Methods: Baseline serum CD40L (sCD40L) was measured in incident MI (n = 368) and stroke (n = 304) cases and two controls per case, 'nested' in prospective UK studies of 4252 men and 4286 women aged 60-79 years, sampled from general practices in Britain in 1998-2000, with 7-year follow-up for fatal and non-fatal MI and stroke., Results: sCD40L was higher in smokers and negatively associated with lung function and positively associated with total cholesterol and markers of inflammation, but not with other established cardiovascular disease (CVD) risk factors. Geometric mean sCD40L levels did not differ between MI cases and controls (5.94 ng mL(-1) vs. 5.82 ng mL(-1); P = 0.5) or between stroke cases and controls (5.61 ng mL(-1) vs. 5.28 ng mL(-1), P = 0.1). There was no strong evidence for elevated risk of MI or stroke in multivariable models comparing participants in the top to those in the bottom third of sCD40L. Age-adjusted odds ratios (ORs) were 1.39 [95% confidence interval (CI) 0.98, 1.96] for MI and 1.16 (0.78, 1.73) for stroke. These attenuated to 1.24 (95% CI 0.86, 1.79) and 1.18 (0.78, 1.78), respectively, after adjustment for established and novel CVD risk factors., Conclusions: sCD40L is associated with other inflammatory markers but is not itself a strong independent risk marker for either stroke or MI., (© 2011 International Society on Thrombosis and Haemostasis.)

Objectives: To examine whether second-hand smoke (SHS) exposure measured by serum cotinine is associated with increased coronary heart disease (CHD) and stroke risk among contemporary older British adults., Design: Prospective population-based study with self-reported medical history and health behaviours. Fasting blood samples were analysed for serum cotinine and cardiovascular disease (CVD) risk markers., Setting: Primary care centres in 25 British towns in 1998-2001., Patients: 8512 60-79-year-old men and women selected from primary care registers., Main Outcome Measures: Fatal and non-fatal myocardial infarction (MI; n=445) and stroke (n=386) during median 7.8-year follow-up., Main Exposure: Observational study of serum cotinine assayed from fasting blood sample using liquid chromatography tandem mass spectrometry method, and self-reported smoking history., Results: Among 5374 non-smokers without pre-existing CVD, geometric mean cotinine was 0.15 ng/ml (IQR 0.05-0.30). Compared with non-smokers with cotinine < or =0.05 ng/ml, higher cotinine levels (0.06-0.19, 0.2-0.7 and 0.71-15.0 ng/ml) showed little association with MI; adjusted HRs were 0.92 (95% CI 0.63 to 1.35), 1.07 (0.73 to 1.55) and 1.09 (0.69 to 1.72), p(trend)=0.69. Equivalent HRs for stroke were 0.82 (0.55 to 1.23), 0.74 (0.48 to 1.13) and 0.69 (0.41 to 1.17), p(trend)=0.065. The adjustment for sociodemographic, behavioural and CVD risk factors had little effect on the results. The HR of MI for smokers (1-9 cigarettes/day) compared with non-smokers with cotinine < or =0.05 ng/ml was 2.14 (1.39 to 3.52) and 1.03 (0.52 to 2.04) for stroke., Conclusions: In contemporary older men and women, SHS exposure (predominantly at low levels) was not related to CHD or stroke risks, but we cannot rule out the possibility of modest effects at higher exposure levels.

Background: Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine implicated in atherosclerotic plaque formation. We investigated whether circulating TNFalpha is prospectively associated with myocardial infarction (MI) or stroke in the older general population, independently of established cardiovascular risk factors and other inflammatory markers related to CHD risk., Methods: We measured baseline TNFalpha concentrations in stored serum samples of 362 incident MI and 299 incident stroke cases and controls (2 per case, frequency matched by age, gender and town) who were 'nested' in parallel prospective studies of 4252 men and 4286 women aged 60-79 years assessed in general practices in 24 British towns in 1998-2000 and followed up for an average 7 years for fatal and non-fatal MI and stroke., Results: TNFalpha levels were 11.4% (95% CI 9.5, 13.3%) higher among MI cases than controls; geometric mean 1.84 pg/mL compared to 1.63 pg/mL, p (difference)<0.001. Participants in the top third of baseline TNFalpha levels had an age-adjusted odds ratio (OR) for MI of 1.75 (95%CI 1.22, 2.49) compared with those in the bottom third, which was reduced to 1.47 (95%CI 1.01, 2.14) after adjustment for established cardiovascular risk factors. However, further adjustment for C-reactive protein and interleukin-6 abolished the association OR 1.33 (95% CI 0.91, 1.66) and the linear trend. Excluding subjects with pre-existing CVD did not materially affect results. No significant association between TNFalpha and stroke was observed., Conclusions: This study suggests that TNFalpha is not a strong independent risk marker for MI, and is not associated with risk of stroke.

Objective: We examined patterns in medication use for secondary prevention of cerebrovascular disease in older British men from 1999 to 2005, and investigated socio-demographic and disease-related influences on medication use., Methods: Percentage use of antiplatelet drugs, blood pressure-lowering drugs and statins use was calculated in men, aged 65-87 years in 2005, who had been diagnosed with stroke or transient ischaemic attack (TIA) from a population-based cohort based in one general practice in each of 24 British towns., Results: In 1999, most men with cerebrovascular disease received antiplatelet drugs (67%). However, a few received blood pressure-lowering drugs (50%) and statins (13%). By 2005, the use of all drug types had increased; at least half of the patients received each type of drug. However, only one-third of patients received all three medication types and combined blood pressure treatment was limited. Older age, a diagnosis of TIA rather than stroke and absence of co-existing coronary heart disease were associated with lower rates of use of specific medication categories., Conclusion: Despite improvements in secondary prevention medication use, there is scope for achieving the full potential of these medications, particularly by increasing combination blood pressure treatment and statin use and ensuring that older patients receive the benefits of prevention.

Background: We sought to compare metabolic syndrome (MetS) with the Framingham Risk Score (FRS) as predictors of coronary heart disease (CHD), stroke, and type 2 diabetes mellitus (DM2) in middle-aged men., Methods: A prospective study of 5128 men aged 40 to 59 years with no history of cardiovascular disease (CVD) (CHD or stroke) or DM2 drawn from general practices in 24 British towns and observed for 20 years. Metabolic syndrome was defined as the presence of 3 or more metabolic abnormalities based on modified National Cholesterol Education Program criteria., Results: Men with MetS at baseline (26%) showed significantly higher relative risk (RR) than men without MetS of developing CHD (RR, 1.64; 95% confidence interval [CI], 1.41-1.90), stroke (RR, 1.61 95% CI, 1.26-2.06), and DM2 (RR, 3.57; 95% CI, 2.83-4.50). The probability of developing CVD or DM2 over 20 years increased from 11.9% in those with no abnormalities to 31.2% in those with 3 abnormalities to 40.8% in those with 4 or 5 abnormalities. The FRS was a better predictor of CHD and stroke than MetS but was less predictive of DM2. Areas under the receiver-operating characteristic curves for FRS vs the number of metabolic abnormalities were 0.68 vs 0.59 for CHD, 0.60 vs 0.70 for DM2, and 0.66 vs 0.55 for stroke (P< .001 for all)., Conclusions: Presence of MetS is a significant predictor of CVD and DM2 but is a stronger predictor of DM2 than of CHD. Although MetS does not predict CHD as well as the FRS, it serves well as a simple clinical tool for identifying high-risk subjects predisposed to CVD or DM2.

Moderate alcohol consumption is associated with a decreased risk of cardiovascular disease. However, the impact of variation in alcohol intake over time on estimated risk relations has not been adequately addressed. In this study, 6,544 middle-aged British men without previous cardiovascular disease were followed for cardiovascular events and all-cause mortality over 20 years from 1978/1980 to 1998/2000. Alcohol intake was ascertained at regular points throughout the study. A total of 922 men had a major coronary event within 20 years, 352 men had a stroke, and 1,552 men died of all causes. Baseline alcohol intake displayed U-shaped relations with cardiovascular disease and all-cause mortality, with light drinkers having the lowest risks and nondrinkers and heavy drinkers having similarly high risks. However, the nature of these relations changed after adjustment for intake variation; risks associated with nondrinking were lowered, and risks associated with moderate and heavy drinking increased. Regular heavy drinkers had a 74% higher risk of a major coronary event, a 133% higher risk of stroke, and a 127% higher risk of all-cause mortality than did occasional drinkers (these estimates were 8%, 54%, and 44% before adjustment for intake variation). The findings suggest that considerable caution may be needed before any recommendations regarding acceptable limits of alcohol consumption are made.

Objective: Lower levels of serum albumin are associated with increased risk of all-cause and cardiovascular mortality as well as with coronary heart disease and stroke incidence. These relationships have been examined with specific focus on the role of cigarette smoking., Study Design and Setting: A prospective study of 7,690 British men aged 40-59 years, with 16.8 years mean follow-up., Results: Cigarette smoking was strongly and inversely associated with serum albumin concentrations that reverted to levels seen in never smokers after 5 years' cessation. Only in current and former smokers were there significant inverse relationships between serum albumin and risk of major CHD and stroke events even after adjustment for potential confounders. Only in current smokers was a significant inverse relationship seen between serum albumin and mortality from cardiovascular disease, cancer, and all causes., Conclusion: The inverse association between serum albumin concentration and disease outcome appears to be related to the effects of cigarette smoking on serum albumin concentration.

Background and Purpose: The purpose of this study was to examine the relation between serum HDL cholesterol and total cholesterol and risk of stroke., Methods: We carried out a prospective study in 7735 men, 40 to 59 years of age, drawn from 1 group practice in each of 24 British towns. Men with history of stroke were excluded (n=52)., Results: During the mean follow-up period of 16.8 years, there were 343 stroke cases (fatal and nonfatal) in the 7683 men with no history of stroke. Higher levels of HDL cholesterol were associated with a significant decrease in risk of stroke even after adjustment for potential confounders (top fifth versus lowest fifth: adjusted relative risk=0.68, 95% CI 0.46 to 0.99). The inverse relation was seen only for nonfatal strokes (adjusted relative risk=0.59, 95% CI 0.39 to 0.90; top fifth versus lowest fifth). Total cholesterol showed no graded association with fatal strokes, but men with levels > or =8.1 mmol/L (top 5% of the distribution) showed increased risk of nonfatal stroke, although this was not statistically significant after adjustment (adjusted RR=1.46, 95% CI 0.91 to 2.32). The beneficial effects of elevated HDL cholesterol on nonfatal stroke were seen in both smokers and nonsmokers and were more evident in men with hypertension than in normotensives. In hypertensive men, elevated HDL cholesterol (top fifth) was associated with a significant 50% reduction in risk of nonfatal strokes compared with men in the lowest fifth., Conclusions: Higher levels of HDL cholesterol were associated with a significant decrease in risk of nonfatal stroke. In contrast, elevated total cholesterol showed a weak positive association with nonfatal strokes. The marked inverse association between HDL cholesterol and stroke seen in hypertensives emphasizes the importance of those modifiable risk factors for stroke known to lower the concentrations of HDL cholesterol.

Most prospective studies have shown physical activity to be associated with a reduced risk of stroke. The results of existing studies suggest that this benefit is seen in both men and women, in younger and older subjects and in subjects with and without pre-existing coronary heart disease. Sporting (vigorous) activity does not appear to be essential to achieve this benefit. Moderate levels of physical activity may be sufficient to achieve a significant reduction in stroke risk and overall cardiovascular risk.