The metabolic syndrome and coronary heart disease in older women: findings from the British Women's Heart and Health Study.

AIMS: To compare two proposed definitions of the metabolic syndrome and to determine the clinical importance of the syndrome with respect to its association with coronary heart disease (CHD). METHODS: Cross-sectional study of 3770 women aged 60-79 years randomly selected from 23 British towns. RESULTS: The prevalence of the metabolic syndrome was high in this population and similar with both definitions: 28.2% (95% confidence interval 26.8, 29.7%) of the women had metabolic syndrome according to a modified version of the WHO definition, and 29.2% (27.7, 30.7%) had the ATP III-defined syndrome. There was reasonable agreement between the two definitions, with 79% of the participants being similarly classified by both definitions. The syndrome was associated with prevalent CHD, with the magnitude of the association with CHD being similar for both definitions. The odds ratio (95% confidence interval) for the age, smoking, physical activity, adult and childhood social class adjusted association of the WHO defined syndrome with prevalent CHD was 1.45 (1.19, 1.75) and for the ATP III-defined syndrome was 1.53 (1.27, 1.85). Insulin resistance alone, hypertension alone and dyslipidaemia alone were all associated with CHD, with the magnitudes of these associations being similar to those for the WHO and ATP III-defined syndrome with CHD. CONCLUSIONS: The prevalence of the metabolic syndrome is high in older British women and is associated with CHD. There is reasonable agreement between a modified version of the WHO definition and the ATP III definition of the syndrome, and both are similarly associated with CHD. Single components of the syndrome are associated with CHD to a similar magnitude as the syndrome.     

Interleukin-6 and incident coronary heart disease: results from the British Women's Heart and Health Study

IntroductionInflammatory mechanisms may play a role in the pathogenesis of atherosclerosis and its complications. Interleukin-6 (IL-6) is an ‘upstream’ pro-inflammatory cytokine that stimulates hepatocytes to synthesize acute phase response proteins such as C-reactive protein (CRP) and fibrinogen. The purpose of this study was to determine whether IL-6 is associated with incident coronary heart disease (CHD) events independently of established risk factors and to examine its predictive ability for future CHD events.MethodsData from the British Women's Heart and Health Study, a prospective cohort of randomly sampled British women 60–79 years old at baseline was used. Three thousand five hundred and eighty-one women had no evidence of coronary heart disease at baseline and were followed up for a median of 4.6 years. Cox proportional hazard models were used to estimate the association of IL-6 with incident CHD.ResultsThe age-adjusted association of IL-6 with the risk of CHD (hazard ratio, HR per doubling of IL-6 = 1.26, 95% CI 1.10, 1.43) was attenuated when adjusting for established CHD risk factors (HR per doubling of IL-6 = 1.13, 95% CI 0.97, 1.31). The main confounders of the association of IL-6 and CHD risk were smoking and forced expiratory volume (FEV₁). Further attenuation was observed when additional terms for components of the metabolic syndrome were added into the model (HR = 1.08, 95% CI 0.93, 1.27).ConclusionsThere was no strong evidence of an association between IL-6 and incident CHD in older British women after controlling for established CHD risk factors. Studies with measures of lung function and socio-economic position are needed to further investigate the role of IL-6 in CHD etiology.     

Avoiding milk is associated with a reduced risk of insulin resistance and the metabolic syndrome: findings from the British Women's Heart and Health Study.

OBJECTIVE: To examine the association of milk consumption with insulin resistance and the metabolic syndrome. METHODS: The association was examined in 4024 British women aged 60-79 who were randomly selected from primary care centres in 23 towns. RESULTS: Women who never drank milk had lower homeostasis model assessment insulin resistance (HOMA) scores, triglyceride concentrations and body mass indices, and higher high-density lipoprotein (HDL)-cholesterol concentrations, than those who drank milk. The age-adjusted odds ratio for the metabolic syndrome comparing non-milk drinkers with drinkers was 0.55 (0.33, 0.94), which did not attenuate with adjustment for potential confounders. Diabetes was less common in non-milk drinkers. CONCLUSION: Individuals who do not drink milk may be protected against insulin resistance and the metabolic syndrome. However, randomized controlled trials are required to establish whether milk avoidance is causally associated with these outcomes.     

The association of life course socio-economic position with diagnosis, treatment, control and survival of women with diabetes: findings from the British Women's Heart and Health Study.

OBJECTIVES: To examine the association of socio-economic position (SEP) with the diagnosis, treatment and control of diabetes, and with survival in women with and without Type 2 diabetes. METHODS: Prospective cohort study of 4277 women from 23 centres in Great Britain, aged 60-79 years at baseline. RESULTS: Of the 4277 women, 220 (5.1%) were known to have Type 2 diabetes and a similar number [n = 188 (4.4%)] had undiagnosed diabetes based on a single fasting glucose level > or = 7.0 mmol/l. Neither childhood nor adult SEP was associated with being correctly diagnosed amongst the 408 women with either diagnosed or undiagnosed diabetes. In both women with and without diabetes, SEP was associated with more adverse levels of fasting insulin, triglycerides, high-density lipoprotein cholesterol and body mass index, but was not associated with glycated haemoglobin in either group. Over the follow-up period, 395 women died. The hazard ratio for all-cause mortality per additional indicator of adverse SEP in adulthood in women with diabetes [1.40 (1.05, 1.85)] was similar to that in women without diabetes [1.26 (1.12, 1.41], P for difference in the two estimates = 0.70). Childhood SEP was not associated with survival. CONCLUSION/INTERPRETATION: A considerable number of older women with Type 2 diabetes are not diagnosed, but SEP is not related to being correctly diagnosed. The marked socio-economic gradient for all-cause mortality is the same for women with and without diabetes and is not fully explained by conventional risk factors.     

Life‐course socio‐economic position,area deprivation and Type 2 diabetes: findings from the British Women's Heart and Health Study

Objectives We examined whether area deprivation influenced risk of Type 2 diabetes, fasting blood glucose and insulin resistance over and above the effect of individual socio‐economic position (SEP) measured across the life course. Methods A cross‐sectional analysis of 4286 women aged 60 to 79 years from 457 British electoral wards in 23 towns. Results Area deprivation was positively associated with diagnosed [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.13, 1.53, per quintile of area deprivation, n = 2895], but not undiagnosed Type 2 diabetes after adjustment for individual life‐course SEP. This association was robust to adjustment for adult health behaviours and physiological risk factors. Insulin resistance [homeostasis model assessment (HOMA) score] increased by 1.90% (95% CI 0.01, 3.82, n = 2526) per quintile of area deprivation after adjustment for individual SEP, while fasting blood glucose increased by 0.69% (95% CI 0.16, 1.22, n = 2875) after adjustment for individual SEP. Conclusions Area level deprivation independently influences diagnosed Type 2 diabetes, insulin resistance and fasting blood glucose. Examination of more specific characteristics of places is needed to understand the mechanisms by which these effects arise.     

A kinesin family member 6 variant is associated with coronary heart disease in the Women's Health Study.

OBJECTIVES: We asked if carriers of the 719Arg allele of kinesin family member 6 (KIF6) have increased risk of coronary heart disease (CHD) in a cohort of initially healthy Caucasian American women. BACKGROUND: The 719Arg allele of KIF6 (rs20455) has been reported to be associated with increased risk of CHD in a large population-based prospective study, ARIC (Atherosclerosis Risk in Communities), and in the placebo arms of 2 statin trials, CARE (Cholesterol and Recurrent Events) and WOSCOPS (West of Scotland Coronary Prevention Study). However, this KIF6 variant was not specifically investigated in the female subgroup in the ARIC study, and the CARE and WOSCOPS trials included only a small number of female patients. METHODS: Genotypes of the rs20455 single nucleotide polymorphism (SNP) were determined among 25,283 initially healthy Caucasian women, age 45 years and older, participating in the WHS (Women's Health Study) who were prospectively followed over a 12-year period for incident cardiovascular events. The risk associated with the 719Arg allele of KIF6 was estimated using Cox proportional hazards models that adjusted for age and traditional risk factors. RESULTS: During follow-up, 953 women suffered a first-ever CHD event (myocardial infarction, coronary revascularization, or cardiovascular death) or first-ever ischemic stroke. Compared with noncarriers, carriers of the 719Arg allele had an increased risk of CHD (hazard ratio [HR] = 1.24 [95% confidence interval (CI) 1.04 to 1.46, p = 0.013]) and myocardial infarction (HR = 1.34 [95% CI 1.02 to 1.75, p = 0.034]) but not ischemic stroke. CONCLUSIONS: Confirming and extending previous reports, carriers of the 719Arg allele of KIF6 have 34% higher risk of myocardial infarction and 24% higher risk of CHD compared with noncarriers among 25,283 women from the WHS.     

Alcohol dehydrogenase type 1C (ADH1C) variants, alcohol consumption traits, HDL-cholesterol and risk of coronary heart disease in women and men: British Women's Heart and Health Study and Caerphilly cohorts

The alcohol dehydrogenase 1C gene (ADH1C) gamma2gamma2 variant reportedly interacts with moderate alcohol consumption to increase HDL-cholesterol levels and reduce coronary heart disease (CHD). We undertook replication studies in two large population cohorts of women and men. 3234 women and 1313 men with relevant genotypic and phenotypic data from two prospective population cohorts were genotyped for ADH1C variants. No association was found between ADH1C variants and HDL-cholesterol, blood pressure or incident CHD, although ADH1C was associated with alcohol consumption. There was no evidence of interactions between ADH1C variants and moderate alcohol intake on HDL-cholesterol, blood pressure or CHD incidence. Life-long women abstainers had adverse risk factor profiles. Our findings do not support the hypothesis that ADH1C variants are associated with CHD risk in people who drink moderately.     

The detection, treatment and control of high blood pressure in older British adults: cross-sectional findings from the British Women's Heart and Health Study and the British Regional Heart Study

Among older people, the detection and control of hypertension is particularly important to reduce cardiovascular disease risk. This cross-sectional survey aimed to describe the detection, treatment and control of hypertension in older British adults. A total of 3059 women and 3007 men aged 60-79 years were randomly selected from general practice age/sex registers in 24 British towns and examined from 1998 to 2001. Of these, 52.6% women and 47.9% men had at least one indicator of hypertension (high blood pressure on examination, or taking antihypertensive medication or recalled a doctor diagnosis of high blood pressure). Among women, 50% of those with any indication of hypertension were on treatment and 29% were well controlled, and among men 45% were on treatment and 16% were well controlled. With the exception of alcohol use in men (adjusted odds ratio 0.67 (0.46, 0.98)), socioeconomic factors, area of residence and behavioural risk factors were not associated with good control among those with hypertension in either sex. Of those on treatment, 20.7% of women and 28% of men were on two classes of antihypertensive medication and 3.5 and 4.9%, respectively, were on three or more classes of antihypertensive medication. Among those with a doctor diagnosis of hypertension and taking antihypertensive medication, the proportion with well controlled blood pressure did not differ between those on more than one antihypertensive and those on just one in either sex. We conclude that targets of good control are rarely met in older individuals, who would benefit from the associated reduction in cardiovascular disease risk.     

Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study

OBJECTIVE: Vitamin D is a potent regulator of calcium homeostasis and may have immunomodulatory effects. The influence of vitamin D on human autoimmune disease has not been well defined. The purpose of this study was to evaluate the association of dietary and supplemental vitamin D intake with rheumatoid arthritis (RA) incidence. METHODS: We analyzed data from a prospective cohort study of 29,368 women of ages 55-69 years without a history of RA at study baseline in 1986. Diet was ascertained using a self-administered, 127-item validated food frequency questionnaire that included supplemental vitamin D use. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards regression, adjusting for potential confounders. RESULTS: Through 11 years of followup, 152 cases of RA were validated against medical records. Greater intake (highest versus lowest tertile) of vitamin D was inversely associated with risk of RA (RR 0.67, 95% CI 0.44-1.00, P for trend = 0.05). Inverse associations were apparent for both dietary (RR 0.72, 95% CI 0.46-1.14, P for trend = 0.16) and supplemental (RR 0.66, 95% CI 0.43-1.00, P for trend = 0.03) vitamin D. No individual food item high in vitamin D content and/or calcium was strongly associated with RA risk, but a composite measure of milk products was suggestive of an inverse association with risk of RA (RR 0.66, 95% CI 0.42-1.01, P for trend = 0.06). CONCLUSION: Greater intake of vitamin D may be associated with a lower risk of RA in older women, although this finding is hypothesis generating.     

Geographical clustering of risk factors and lifestyle for coronary heart disease in the Scottish Heart Health Study

A large cross sectional study, the Scottish Heart Health Study, of 10,359 men and women from 22 districts of Scotland was undertaken to try to explain the geographical variation of coronary heart disease mortality. Analysis by district showed that of the classic risk factors only cigarette smoking was strongly associated with heart disease mortality among both men and women. Mean diastolic blood pressure was weakly associated with rates among men and high density lipoprotein cholesterol showed a strong negative association among women. Total cholesterol showed a weak negative association with heart disease mortality, but, because the serum concentrations of cholesterol were uniformly high in all districts, a strong association with mortality would not be expected. In both men and women many dietary factors showed moderate or strong associations with mortality from coronary heart disease in a district--of these a low consumption of vitamin C was most notable. Other factors associated with heart disease included alcohol consumption and serum triglycerides among men, and obesity, physical activity, and serum triglycerides among women. Many factors associated with heart disease showed strong intercorrelations. Clustering of risk factors (including smoking, alcohol, and diet among men, and smoking, diet, and obesity among women) was associated with much of the regional variation in heart disease mortality in Scotland.     

Geographical clustering of risk factors and lifestyle for coronary heart disease in the Scottish Heart Health Study.

A large cross sectional study, the Scottish Heart Health Study, of 10,359 men and women from 22 districts of Scotland was undertaken to try to explain the geographical variation of coronary heart disease mortality. Analysis by district showed that of the classic risk factors only cigarette smoking was strongly associated with heart disease mortality among both men and women. Mean diastolic blood pressure was weakly associated with rates among men and high density lipoprotein cholesterol showed a strong negative association among women. Total cholesterol showed a weak negative association with heart disease mortality, but, because the serum concentrations of cholesterol were uniformly high in all districts, a strong association with mortality would not be expected. In both men and women many dietary factors showed moderate or strong associations with mortality from coronary heart disease in a district--of these a low consumption of vitamin C was most notable. Other factors associated with heart disease included alcohol consumption and serum triglycerides among men, and obesity, physical activity, and serum triglycerides among women. Many factors associated with heart disease showed strong intercorrelations. Clustering of risk factors (including smoking, alcohol, and diet among men, and smoking, diet, and obesity among women) was associated with much of the regional variation in heart disease mortality in Scotland.     

Frequent nut intake and risk of death from coronary heart disease and all causes in postmenopausal women: the Iowa Women's Health Study

BACKGROUND AND AIM: Recent epidemiological studies suggest that there is an inverse association between the frequent consumption of nuts and the risk of coronary heart disease (CHD), and clinical investigations suggest that diets high in nuts may reduce serum cholesterol levels. This study assessed whether the risk of death due to CHD and all causes is reduced in postmenopausal women who frequently consume nuts. METHODS AND RESULTS: In 1986, 34,111 postmenopausal women with no known cardiovascular disease reported the frequency of their consumption of nuts and other foods, as well as other CHD risk factors. During approximately 12 years of follow-up, 3726 women died, 657 from CHD. After adjustment for multiple risk factors for CHD and dietary variables, there was an inverse but not statistically significant association between frequent nut consumption (two or more 28.5 g servings per week compared with less than one serving per month) and death from CHD (relative risk 0.81; 95% confidence interval: 0.60-1.11). There was also a weak inverse association between frequent nut intake and all-cause mortality (relative risk 0.88; 95% confidence interval: 0.77-0.99, p for trend = 0.047). CONCLUSIONS: Frequent nut consumption may offer postmenopausal women modest protection against the risk of death from all causes and CHD.     

Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study

BACKGROUND: Depression leads to adverse outcomes in patients with coronary heart disease (CHD). Medication nonadherence is a potential mechanism for the increased risk of CHD events associated with depression, but it is not known whether depression is associated with medication nonadherence in outpatients with stable CHD. METHODS: We examined the association between current major depression (assessed using the Diagnostic Interview Schedule) and self-reported medication adherence in a cross-sectional study of 940 outpatients with stable CHD. RESULTS: A total of 204 participants (22%) had major depression. Twenty-eight (14%) of 204 depressed participants reported not taking their medications as prescribed compared with 40 (5%) of 736 nondepressed participants (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.7-4.7; P<.001). Twice as many depressed participants as nondepressed participants (18% vs 9%) reported forgetting to take their medications (OR, 2.4; 95% CI, 1.6-3.8; P<.001). Nine percent of depressed participants and 4% of nondepressed participants reported deciding to skip their medications (OR, 2.2; 95% CI, 1.2-4.2; P = .01). The relationship between depression and nonadherence persisted after adjustment for potential confounding variables, including age, ethnicity, education, social support, and measures of cardiac disease severity (OR, 2.2; 95% CI, 1.2-3.9; P = .009 for not taking medications as prescribed). CONCLUSIONS: Depression is associated with medication nonadherence in outpatients with CHD. Medication nonadherence may contribute to adverse cardiovascular outcomes in depressed patients.     

High molecular weight adiponectin is not associated with incident coronary heart disease in older women: a nested prospective case-control study

CONTEXT: Adiponectin levels appear weakly linked to incident vascular disease, but the high molecular weight (HMW) fraction may be more relevant. OBJECTIVE: Our objective was to test whether HMW adiponectin, the key biologically active fraction, is linked to incident coronary heart disease (CHD) events. DESIGN, PARTICIPANTS, AND MAIN OUTCOME MEASURES: We assessed the association between HMW adiponectin (measured by ELISA) and CHD risk in a prospective (4-yr) case-control study nested within the British Women's Heart and Health Study. All women were postmenopausal. SETTING: Women were seen in a primary care setting. RESULTS: Among both cases (n = 167) and controls (n = 333), HMW adiponectin positively correlated with age and high-density lipoprotein cholesterol and inversely correlated with waist to hip ratio, fasting insulin, fasting glucose, homeostasis model assessment for insulin resistance scores, C-reactive protein, and triglycerides, in similar fashion to total adiponectin. The age-adjusted relative risk ratio for a doubling of HMW adiponectin was 0.96 (95% confidence interval, 0.78-1.18), and adjustment for any of the potential confounding or mediating variables did not substantively alter this. Additional adjustments for childhood social class, alcohol consumption, hormone replacement therapy use, statin, aspirin, or blood pressure medication did not alter the null association. When we examined the effect of HMW adiponectin by quarters of its distribution, there was no evidence of any associations (P trend = 0.71). There was also no association of the ratio of HMW adiponectin to total adiponectin with CHD risk; age-adjusted relative risk per doubling of the ratio was 1.10 (95% confidence interval, 0.80-1.50). CONCLUSIONS: Despite associations with total adiponectin and insulin resistance, our data go against any apparent association between HMW adiponectin levels and incident CHD events.