Sarah H. Wild

Cardiovascular disease in women with polycystic ovary syndrome at long‐term follow‐up: a retrospective cohort study

Polycystic ovary syndrome (PCOS) is associated with higher prevalence of cardiovascular risk factors but the relative prevalence of cardiovascular disease in women with PCOS has not previously been reported. We have compared cardiovascular mortality and morbidity in middle‐aged women previously diagnosed with PCOS and age‐matched control women.

Mortality of Women with Polycystic Ovary Syndrome at Long-term Follow-up

Metabolic disturbances associated with insulin resistance are present in most women with polycystic ovary syndrome. This has led to suggestions that women with polycystic ovary syndrome may be at increased risk of cardiovascular disease in later life. We undertook a long-term follow-up study to test whether cardiovascular mortality is increased in these women. A total of 786 women diagnosed with polycystic ovary syndrome in the United Kingdom between 1930 and 1979 were traced from hospital records and followed for an average of 30 years. Standardized mortality ratios (SMRs) were calculated to compare the death rates of these women with national rates. The SMR for all causes was 0.90 (95% CI, 0.69-1.17), based on 59 deaths. There were 15 deaths from circulatory disease, yielding an SMR of 0.83 (95% CI, 0.46-1.37). Of these 15 deaths, 13 were from ischemic heart disease (SMR 1.40; 95% CI, 0.75-2.40) and two were from other circulatory disease (SMR 0.23; 95% CI, 0.03-0.85). There were six deaths from diabetes mellitus as underlying or contributory cause, compared with 1.7 expected (odds ratio 3.6; 95% CI, 1.5-8.4). Breast cancer was the commonest cause of death (SMR 1.48 based on 13 deaths; 95% CI, 0.79-2.54). We conclude that women with polycystic ovary syndrome do not have markedly higher than average mortality from circulatory disease, even though the condition is strongly associated with diabetes, lipid abnormalities, and other cardiovascular risk factors. The characteristic endocrine profile of women with polycystic ovary syndrome may protect against circulatory disease in this condition.

Long-term consequences of polycystic ovary syndrome: Results of a 31 year follow-up study

A cohort of 786 women who received a diagnosis of polycystic ovary syndrome (PCOS) in the United Kingdom before 1979 was traced to investigate the long-term consequences of the syndrome. Data were obtained from death certificates for 70 women. Morbidity data were collected from general practice records and questionnaires for 319 women diagnosed with PCOS an average of 31 years previously and for 1060 age-matched control women. The proportion of women with involuntary infertility was 17.5% in the PCOS group compared with 1.3% in the control group. All-cause mortality in the cohort did not differ from that of the general population of women. Women with PCOS were not at significantly increased risk of mortality or morbidity from breast cancer but were at increased risk of endometrial cancer. Women with a history of PCOS had higher levels of several cardiovascular risk factors including diabetes, hypertension, raised plasma cholesterol and body mass index > 30 kg m-2. Mortality and morbidity from coronary heart disease did not differ significantly between the women with PCOS and comparison groups. Control of obesity is likely to be particularly important for women with a history of PCOS.

A Prospective Case-Control Study of Lipoprotein(a) Levels and Apo(a) Size and Risk of Coronary Heart Disease in Stanford Five-City Project Participants

Lipoprotein(a) [Lp(a)] is formed by the assembly of LDL particles and a carbohydrate-rich protein, apolipoprotein(a) [apo(a)], which has a high degree of structural homology with plasminogen. While the majority of retrospective studies have found an association between Lp(a) level and cardiovascular disease (CVD), the few prospective studies to date have reported contradictory results. We conducted a nested case-control study using the participants in the Stanford Five-City Project, a long-term CVD prevention trial. Participants with an incident possible or definite myocardial infarction or coronary death were matched to a single control subject for age, sex, ethnicity, residence in a treatment or control city, and time of survey. This process yielded 134 case-control pairs, 90 male and 44 female, for whom plasma was available for analysis of Lp(a). Lp(a) values in nanomoles per liter were determined by an enzyme-linked immunoassay that measures Lp(a) independently of apo(a) size polymorphism. Apo(a) size isoforms were determined by SDS-agarose gel electrophoresis. Median Lp(a) level in male cases was almost double that in control subjects (41.8 versus 21.2 nmol/L; P < .01); in female cases, median Lp(a) was 34% higher than in control subjects (32.5 versus 21.2 nmol/L), but this difference was not statistically significant. Among the male cases, there was an increased frequency of small apo(a) isoforms, while no significant difference was found in apo(a) size between female cases and control subjects. The association between Lp(a) level and case-control status in men was independent of total, HDL, and non-HDL cholesterol levels, as well as apo(a) size isoform, cigarette smoking, blood pressure, and obesity. In men, the most efficient threshold value of Lp(a) concentration for separating cases and control subjects was 35 nmol/L; the odds ratio for being a case above this level compared with below was 2.84 (95% confidence interval: 1.53-5.27, P < .001). This study provides strong evidence that Lp(a) level is a prospective, independent risk factor for developing coronary artery disease in men and indicates that the size of apo(a) may also play a role. The lack of a significant association in women deserves further evaluation in larger studies.

Mortality from coronary heart disease and stroke for six ethnic groups in California, 1985 to 1990☆

Coronary heart disease and stroke death rates were compared for six ethnic groups (non-Hispanic white, Hispanic, African-American, Chinese, Japanese, and Asian Indian) by sex and age (25 to 44, 45 to 64, 65 to 84, and 25 to 84 years old) using California census and 1985 to 1990 death data. African-American men and women in all age groups had the highest rates of death from coronary heart disease, stroke, and all causes (except for coronary heart disease in the oldest men). Hispanics, Chinese, and Japanese in all age-sex groups had comparatively low death rates for coronary heart disease and stroke, although stroke was proportionally an important cause of death for Chinese and Japanese groups. Coronary heart disease was an important cause of death for Asian Indians although death rates were generally not higher than those for other ethnic groups. Ethnic differences were most marked for women and younger age groups.

All-cause and cardiovascular mortality among Koreans: effects of obesity and metabolic health

INTRODUCTION The effect of obesity on mortality in people with metabolic syndrome (MetS) risk factors, but without pre-existing diabetes; hypertension; or cardiovascular disease (CVD), is uncertain. The purpose of this study is to investigate the effect of obesity and MetS risk factors on CVD and all-cause mortality in an Asian cohort. METHODS This retrospective study included 275,867 Koreans (56.6% men) who participated in an occupational health program between 2002 and 2009. At baseline, four groups were defined, according to the absence/presence of obesity (defined by BMI < or ≥25, respectively) and zero or one or more MetS features, respectively: metabolically healthy non-obese (MHNO; reference group); metabolically healthy obese (MHO); metabolically unhealthy obese (MUO); and metabolically unhealthy non-obese (MUNO). Hazard ratios (HRs) and 95% CIs for CVD and all-cause mortality at follow-up were estimated using Cox proportional hazards models. RESULTS During follow-up, 1,060 deaths (187 from CVD) occurred. After adjusting for age, sex, alcohol intake, exercise, and educational status, CVD mortality risk was not increased in the MHO group (HR=0.50, 95% CI=0.15, 1.66), whereas risk was increased in the MUO and MUNO groups (HR=1.81, 95% CI=1.12, 2.91; HR=1.84, 95% CI=1.15, 2.92, respectively). HRs for all-cause mortality in both obese groups were not different from the reference group. When subjects with prior diabetes, CVD, and hypertension were excluded, CVD mortality was not significantly different in the MUO and MUNO groups from the reference group. CONCLUSIONS Comorbid diabetes, hypertension, or CVD explain much of the increased risk of CVD mortality in obese individuals.

Predicting incident fatty liver using simple cardio-metabolic risk factors at baseline

BackgroundNon alcoholic fatty liver disease (NAFLD) is associated with increased risk of type 2 diabetes and chronic liver disease but identifying patients who have NAFLD without resorting to expensive imaging tests is challenging. In order to help identify people for imaging investigation of the liver who are at high risk of NAFLD, our aim was to: a) identify easily measured risk factors at baseline that were independently associated with incident fatty liver at follow up, and then b) to test the diagnostic performance of thresholds of these factors at baseline, to predict or to exclude incident fatty liver at follow up.Methods2589 people with absence of fatty liver on ultrasound examination at baseline were re-examined after a mean of 4.4 years in a Korean occupational cohort study. Multi-variable logistic regression analyses were used to identify baseline factors that were independently associated with incident fatty liver at follow up. The diagnostic performance of thresholds of these baseline factors to identify people with incident fatty liver at follow-up was assessed using receiver operating characteristic (ROC) curves.Results430 incident cases of fatty liver were identified. Several factors were independently associated with incident fatty liver: increased triglyceride (per mmol/l increase) OR 1.378 [95%CIs 1.179, 1.611], p < 0.0001; glucose (per mmol/l increase) OR 1.215 [95%CIs 1.042, 1.416], p = 0.013; waist (per cm increase) OR 1.078 [95%CIs 1.057, 1.099], p < 0.001; ALT (per IU/L increase) OR 1.009 [95%CIs 1.002, 1.017], p = 0.016; and platelets (per 1x109/L increase) OR 1.004 [1.001, 1.006], p = 0.001; were each independently associated with incident fatty liver. Binary thresholds of the five factors were applied and the area under the ROC curve for incident fatty liver was 0.75 (95%CI 0.72–0.78) for the combination of all five factors above these thresholds.ConclusionSimple risk factors that overlap considerably with risk factors for type 2 diabetes allow identification of people at high risk of incident fatty liver at who use of hepatic imaging could be targeted.

LIPIDS AND SECONDARY PREVENTION OF ISCHAEMIC HEART DISEASE

Ischaemic heart disease remains the major cause of death for men and women in the developed world and, with stroke, is a key area for health promotion in The Health of the Nation.1 The importance of primary prevention (reducing risk in people with no evidence of disease) is highlighted by the fact that about a quarter of new cases of ischaemic heart disease present as sudden death.2 Secondary prevention (reducing risk in people with evidence of disease) should be approached with the same vigour as primary prevention because morbidity and mortality from ischaemic heart disease have considerable social and financial implications for individuals as well as communities. Measures that improve survival after myocardial infarction include treatment with thrombolytic agents, aspirin, and s adrenergic blockers, and stopping smoking. Lowering serum lipid concentrations in patients with ischaemic heart disease and hypercholesterolaemia has been shown to reduce the risk of subsequent cardiovascular death. Concerns have been raised that the cardiovascular benefits of lowering cholesterol concentrations might be outweighed by the increased risk of other causes of death. However, the Scandinavian simvastatin survival study (4S), a large randomised, placebo controlled trial of simvastatin in patients with ischaemic heart disease and total cholesterol concentrations of 5.5-8.0 mmol/l, showed significant improvements in mortality from ischaemic heart disease with no evidence of increased mortality from non-cardiovascular causes …