Risk of stroke in people with type 2 diabetes in the UK: a study using the General Practice Research Database

Aims/hypothesis Risk estimates for stroke in patients with diabetes vary. We sought to obtain reliable risk estimates for stroke and the association with diabetes, comorbidity and lifestyle in a large cohort of type 2 diabetic patients in the UK.Materials and methods Using the General Practice Research Database, we identified all patients who had type 2 diabetes and were aged 35 to 89 years on 1 January 1992. We also identified five comparison subjects without diabetes and of the same age and sex. Hazard ratios (HRs) for stroke between January 1992 and October 1999 were calculated, and the association with age, sex, body mass index, smoking, hypertension, atrial fibrillation and duration of diabetes was investigated.Results The absolute rate of stroke was 11.91 per 1,000 person-years (95% CI 11.41–12.43) in people with diabetes (n = 41,799) and 5.55 per 1,000 person-years (95% CI 5.40–5.70) in the comparison group (n = 202,733). The age-adjusted HR for stroke in type 2 diabetic compared with non-diabetic subjects was 2.19 (95% CI 2.09–2.32) overall, 2.08 (95% CI 1.94–2.24) in men and 2.32 (95% CI 2.16–2.49) in women. The increase in risk attributable to diabetes was highest among young women (HR 8.18; 95% CI 4.31–15.51) and decreased with age. No investigated comorbidity or lifestyle characteristic emerged as a major contributor to risk of stroke.Conclusions/interpretation This study provides risk estimates for stroke for an unselected population from UK general practice. Patients with type 2 diabetes were at an increased risk of stroke, which decreased with age and was higher in women. Additional risk factors for stroke in type 2 diabetic patients included duration of diabetes, smoking, obesity, atrial fibrillation and hypertension.     

All-cause mortality rates in patients with type 1 diabetes mellitus compared with a non-diabetic population from the UK general practice research database, 1992–1999

Aims/hypothesis We compiled up to date estimates of the absolute and relative risk of all-cause mortality in patients with type 1 diabetes in the UK. Materials and methods We selected patients with type 1 diabetes (n=7,713), and for each of these diabetic subjects five age- and sex-matched control subjects without diabetes (n=38,518) from the General Practice Research Database (GPRD). Baseline was 1 January 1992; subjects were followed until 1999. The GPRD is a large primary-care database containing morbidity and mortality data of a large sample representative of the UK population. Deaths occurring in the follow-up period were identified. Results The study comprised 208,178 person-years of follow-up. The prevalence of type 1 diabetes was 2.15/1,000 subjects in 1992 (mean age 33 years, SD 15). Annual mortality rates were 8.0 per 1,000 person-years (95% CI 7.2-8.9) in type 1 diabetic subjects compared with 2.4 per 1,000 person−years (95% CI 2.2-2.6) in those without diabetes (hazard ratio [HR]=3.7, 95% CI 3.2-4.3). The increased mortality rates in patients with type 1 diabetes were apparent across all age-bands. The HR was higher in women (HR=4.5, 95% CI 3.5-5.6 compared with non-diabetic women) than men (HR=3.3, 95% CI 2.7-4.0), such that the sex difference (p<0.0001) in mortality in the non-diabetic population was abolished (p=0.3) in the type 1 diabetic patients. The predominant cause of death in patients with type 1 diabetes was cardiovascular disease. Conclusions/interpretation Despite advances in care, UK mortality rates in the past decade continue to be much greater in patients with type 1 diabetes than in those without diabetes.     

Type 2 diabetes mellitus is a risk factor for the development of hypertension in postmenopausal women

OBJECTIVE: Hypertension and type 2 diabetes mellitus are common diseases that are frequently found concomitantly in postmenopausal women. These findings suggest a close and/or synergistic nature in the relationship between the two disease processes; however, no prospective data exist on the incidence rate of hypertension in postmenopausal women with type 2 diabetes mellitus. METHODS: The present study assessed the risk of developing hypertension in 840 postmenopausal women: 102 women (12.1% of the cohort) with type 2 diabetes mellitus and 738 (87.9%) free of diabetes. The mean +/- SD follow-up was 3.2 +/- 0.9 years (range 0.5-6.0 years). RESULTS: The incidence rate (cases of hypertension per 100 person-years) was 1.1 for the group of women without diabetes versus 5.6 in women with diabetes (P < 0.0001). Compared with the non-diabetic group, women with type 2 diabetes mellitus had a statistically significant higher risk of developing hypertension. The relative risks for women with diabetes was 5.09 [crude: 95% confidence interval (CI) = 3.52-7.36; P < 0.0001]; 3.43 (adjusted for body mass index and waist circumference: 95% CI = 2.25-5.14; P < 0.001); and 2.95 (adjusted for all potential confounders: 95% CI = 1.86-4.32; P < 0.01). CONCLUSION: In our prospective study, on the incidence of hypertension, the presence of type 2 diabetes was found to be a potent independent risk determinant. This suggests that postmenopausal women affected by type 2 diabetes mellitus comprise a population at high risk for the subsequent development of hypertension.     

Impact of gender on relative rates of cardiovascular events in patients with diabetes

AimTo investigate whether diabetes confers higher relative risks of cardiovascular events in women compared with men using contemporary data and also whether such gender-differences are dependent on age.MethodsAll patients discharged from French hospitals in 2013 with at least 5 years of follow-up and no history of major adverse cardiovascular events including heart failure (MACE-HF; heart failure, myocardial infarction, ischaemic stroke, cardiovascular death) were identified and categorized by diabetes status. Overall and age-stratified incidence rates, hazard ratios (HRs) and women-to-men ratios (WMRs) for MACE-HF leading to hospitalization were also calculated. Adjustments were then made for age and baseline characteristics according to cardiovascular risk factors and non-cardiovascular comorbidities.ResultsThe study included 2,953,816 subjects, among whom 349,928 (11.9%) had diabetes. Of those with diabetes, the absolute rate of MACE-HF was higher in men than in women (96 vs 66 per 1000 person-years); corresponding absolute rates in men and women without diabetes were 44 vs 27 per 1000 person-years. Comparing those with and without diabetes, women had a higher unadjusted HR of MACE-HF (2.45, 95% CI: 2.42–2.47) than men (2.15, 95% CI: 2.14–2.17), with an adjusted WMR of 1.13 (95% CI: 1.12–1.15). HRs of MACE-HF related to diabetes were highest in women aged around 45 years and in the youngest men and decreased with advancing age in both these groups. However, HRs were higher in women of all ages > 40 years. After adjustment, this effect was more apparent for myocardial infarction (adjusted WMR: 1.43, 95% CI: 1.38–1.48) than for either ischaemic stroke (adjusted WMR: 1.10, 95% CI: 1.07–1.14) or heart failure (adjusted WMR: 1.13, 95% CI: 1.11–1.14).ConclusionAlthough men have higher absolute risks of cardiovascular complications, the relative risks of cardiovascular complications associated with diabetes are higher in women than in men.     

Incidence and predictors of drug-treated diabetes in elderly French subjects. The PAQUID Epidemiological Survey.

AIMS: To estimate the incidence and predictors of drug-treated diabetes in elderly subjects. METHODS: The PAQUID epidemiological survey, a population-based study, has followed up 3,777 subjects older than 65 years since 1988. At each visit (baseline, 1, 3, 5 and 8 years), treatment regimen was used to identify new drug-treated diabetic subjects. Potential predictors of drug-treated diabetes were collected during the baseline visit (body mass index (BMI), educational level, cigarette smoking and wine consumption, physical activity, depressive symptomatology, subjective health, treatment, and hypertension) and analysed by using a multivariate backward stepwise regression Cox model with delayed entry. RESULTS: The prevalence rate of drug-treated diabetes was 7.5% at baseline and 7.1% after 8 years' follow-up. The incidence rate of drug-treated diabetes was 3.8/1,000 person-years, 5.9/1,000 person-years in men and 2.4/1,000 person-years in women, with no significant variation according to age group. Male sex (relative risk (RR) 2.4, 95% confidence interval (CI) 1.4-4.0, P < 0.001, attributable risk (AR) 0.36), elevated BMI (for one point increase, RR 1.1, 95% CI 1.1-1.1, P < 0.001, > or = 25 vs. < 25, RR 2.1, 95% CI 1.2-3.5, AR 0.33), thiazide diuretics used alone (RR 5.9, 95% CI 1.8-19.6, P = 0.02), and poorer subjective health ('the same' vs. 'better' RR 1.8, 95% CI 1.0-3.1, P = 0.04; 'worse' vs. 'better' RR 2.3, 95% CI 0.9-5.7, P = 0.06) were independent predictors of drug-treated diabetes in this population. CONCLUSIONS: In older French individuals, men seem to be particularly exposed to drug-treated diabetes although being overweight was found to be a strong predictor as in younger populations.     

Finnish Diabetes Risk Score to predict type 2 diabetes in the Isfahan diabetes prevention study

Aim

The strong association between the Finnish Diabetes Risk Score (FINDRISC) and risk of diabetes reported in European populations cannot necessarily be generalized to other populations. The aim of this study was to evaluate the ability of FINDRISC to predict progression to diabetes in an Iranian population without diabetes.

Methods

A total of 1537 first-degree relatives (FDR) without diabetes of consecutive people with type 2 diabetes 30–70 years old (376 men and 1161 women) were examined and followed for a mean (SD) of 7.8 (1.7) years for diabetes incidence. We examined the incidence of diabetes across quartiles of FINDRISC and plotted a receiver operating characteristic (ROC) curve to assess discrimination. At baseline and through follow-up, participants underwent a standard 75-g 2-h oral glucose tolerance test. Data for the FINDRISC were available from each participant.

Results

During 12,046 person-years of follow-up, 41 men and 154 women developed diabetes. The incidence of type 2 diabetes was 14.0 per 1000 person-years in men and 16.9 in women. Those in the top quartile of FINDRISC were 21.7 times more likely to develop diabetes than those in the bottom quartile (relative risk 21.7; 95% CI 9.90, 47.39). The area under the ROC was 75.1% (95% CI 71.3, 78.8).

Conclusions

The results of this study show that FINDRISC is a robust predictor of type 2 diabetes in high-risk individuals in Iran.     

Excess risk of diabetes in persons with hypertension

ProblemPersons with hypertension appear to be at increased risk of diabetes, an important predictor of cardiovascular disease. Whether, and to what extent, this risk may vary across subgroups defined on the basis of important clinical characteristics has not been well characterized.MethodsStudy population included members of Kaiser Permanente Northwest Region, a large health maintenance organization, aged ≥35 years and free of diabetes in 1998. Persons in the study population were stratified based on whether or not they had hypertension, and onset of diabetes was ascertained over a 6-year period beginning January 1999. Excess risk of diabetes was characterized in terms of risk differences between persons with and without hypertension, and was estimated on an overall basis and for subgroups defined on the basis of age, sex, and body mass index (BMI).ResultsStudy population totaled 104,368; 44% had hypertension. Relative risk (RR) of developing diabetes was 2.7 (95% CI: 2.6–2.8) for those with vs. without hypertension [21.0 (95% CI: 20.7–21.4) vs. 7.8 (95% CI: 7.6–8.0) per 1000 person-years, respectively]. Adjusted for age, sex, and BMI, RR of diabetes was 1.8 (95% CI: 1.7–1.9). With one exception (men, aged ≥75 years), risk of diabetes was higher across all age and BMI strata for both men and women with vs. without hypertension; differences in risk were greatest among those with high BMI (≥35 kg/m²). Across BMI strata, RR of developing diabetes was generally higher at younger ages.ConclusionAll persons with hypertension, irrespective of age, sex, and BMI, are at elevated risk of developing diabetes. Men and women with hypertension who are overweight or obese are at substantially elevated risk of diabetes, regardless of age, and should be monitored especially closely for the development of this disease.     

Alcohol consumption and risk of coronary heart disease among men with type 2 diabetes mellitus

OBJECTIVES

The goal of this study was to examine the relationship between alcohol intake and risk of coronary heart disease (CHD) among men with type 2 diabetes.

BACKGROUND

Type 2 diabetes is associated with an increased risk of CHD. Emerging evidence suggests that moderate alcohol intake is associated with an important reduction in risk of CHD in individuals with type 2 diabetes.

METHODS

We studied 2,419 men who reported a diagnosis of diabetes at age 30 or older in the Health Professionals’ Follow-up study (HPFS). During 11,411 person-years of follow-up after diagnosis, we documented 150 new cases of CHD (81 nonfatal myocardial infarction [MI] and 69 fatal CHD). Relative risks (RR) were estimated from pooled logistic regression adjusting for potential confounders.

RESULTS

Alcohol use was inversely associated with risk of CHD in men with type 2 diabetes. The age-adjusted RRs corresponding to intakes of ≤0.5 drinks/day, 0.5 to 2 drinks/day and >2 drinks/day were 0.76 (95% confidence interval: [CI]: 0.52 to 1.12), 0.64 (95% CI: 0.40 to 1.02) and 0.59 (95% CI: 0.32 to 1.09), respectively, as compared with nondrinkers (p for TREND = 0.06). When we controlled for body mass index, smoking, family history of MI, hypertension, hypercholesterolemia, duration of diabetes, physical activity level, vitamin E supplements and intake of trans fat, polyunsaturated fat, fiber and folate, RRs were 0.78 (95% CI: 0.52 to 1.15), 0.62 (95% CI: 0.40 to 1.00) and 0.48 (95% CI: 0.25 to 0.94) (p for TREND = 0.03). The benefits of moderate consumption did not statistically differ by beverage type.

CONCLUSIONS

Moderate alcohol consumption is associated with lower risk of CHD in men with type 2 diabetes.     

Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup

Background and Aim: The question of whether fatty liver might predict impaired fasting glucose or type 2 diabetes mellitus in a longitudinal manner was assessed in Japanese subjects undergoing a health checkup. Methods: A total of 12 375 individuals (6799 men and 5576 women) without hyperglycemia or type 2 diabetes mellitus in 2000 and participating in 2005 were included. Multiple logistic regression analyses were performed for both sexes, adjusted for age, body mass index, elevated blood pressure or hypertension, family history of diabetes mellitus, alcohol drinking and smoking. Results: Impaired fasting glucose and type 2 diabetes mellitus were newly diagnosed in 7.6% and 1.0% of men and 3.8% and 0.5% of women, respectively, within the 5‐year period. The prevalence of newly diagnosed impaired fasting glucose and type 2 diabetes mellitus was significantly higher in the participants with fatty liver than without fatty liver in both sexes. Fatty liver adjusted for the other factors was thus a risk factor for impaired fasting glucose and/or type 2 diabetes mellitus in both sexes (men odds ratio [OR] 1.91, 95% confidence interval [CI] 1.56–2.34 and women OR 2.15, 95% CI 1.53–3.01). The impact of fatty liver was stronger among the participants with a lower body mass index (men OR 0.92, 95% CI 0.86–0.99 and women OR 0.90, 95% CI 0.81–0.99, for one increment of body mass index). Conclusion: Fatty liver is an independent risk factor for impaired fasting glucose and type 2 diabetes mellitus, having a stronger impact in those Japanese with a lower body mass index undergoing a health checkup.     

Sex differences in risk for coronary heart disease mortality associated with diabetes and established coronary heart disease

BACKGROUND: The sex-specific independent effect of diabetes mellitus and established coronary heart disease (CHD) on subsequent CHD mortality is not known. METHODS: This is an analysis of pooled data (n = 5243) from the Framingham Heart Study and the Framingham Offspring Study with follow-up of 20 years. At baseline (1971-1975), 134 men and 95 women had diabetes, while 222 men and 129 women had CHD. Risk for CHD death was analyzed by proportional hazards models, adjusting for age, hypertension, serum cholesterol levels, smoking, and body mass index. The comparative effect of established CHD vs diabetes on the risk of CHD mortality was tested by testing the difference in log hazards. RESULTS: The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for death from CHD were 2.1 (95% CI, 1.3-3.3) in men with diabetes only, and 4.2 (95% CI, 3.2-5.6) in men with CHD only compared with men without diabetes or CHD. The HR for CHD death was 3.8 (95% CI, 2.2-6.6) in women with diabetes, and 1.9 (95% CI, 1.1-3.4) in women with CHD. The difference between the CHD and the diabetes log hazards was +0.73 (95% CI, 0.72-0.75) in men and -0.65 (95% CI, -0.68 to -0.63) in women. CONCLUSIONS: In men, established CHD signifies a higher risk for CHD mortality than diabetes. This is reversed in women, with diabetes being associated with greater risk for CHD mortality. Current treatment recommendations for women with diabetes may need to be more aggressive to match CHD mortality risk.     

Evaluation of the Finnish Diabetes Risk Score (FINDRISC) as a Screening Tool for the Metabolic Syndrome

OBJECTIVES: Traditionally, the Finnish Diabetes Risk Score (FINDRISC) questionnaire is a screening tool to estimate risk of type 2 diabetes. In this study, we evaluated the ability of FINDRISC to predict the development of the metabolic syndrome (MetS) in an Iranian population without diabetes and MetS. METHODS: A total of 1,010 first-degree relatives of consecutive patients with type 2 diabetes, 30-70 years old (274 men and 736 women), without diabetes and MetS, were examined and followed up over 8.0 ± 1.6 years (mean ± SD) for MetS incidence. The incidence of MetS was examined across quartiles of FINDRISC, and a receiver operating characteristic (ROC) curve was plotted to assess the discrimination. At baseline and through follow-ups, participants underwent a standard 75 g 2-hour oral glucose tolerance test (OGTT). Data for determining FINDRISC were available from each participant. RESULTS: During 8,089 person-years of follow-up, 69 men and 209 women without MetS and diabetes at baseline subsequently developed MetS. The incidence of MetS was 31.4 per 1000 person-years in men and 35.5 in women. The FINDRSC at baseline was significantly associated with MetS evolution. Participants in the top quartile of FINDRISC were 4.4 times more likely to develop MetS than those in the bottom quartile (rate ratio 4.4; 95% CI 2.7-7.0). The area under the ROC curve was 65.0% (95% CI 61.3-68.7). CONCLUSION: The results of this study suggest that FINDRISC can be applied to detect MetS in a high-risk population.     

Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors

The extent to which sodium-glucose co-transporter-2 (SGLT2) inhibitors increase the risk of genital infections in routine clinical care, compared with other antidiabetic medications, is not clear, or whether the increased risk is consistent across gender or age subgroups, within individual SGLT2 agents, or if it is more pronounced at a particular time after treatment initiation. We conducted a retrospective cohort study using two US commercial claims databases (2013-2017). In the primary analysis, 1:1 propensity score-matched cohorts of female and male subjects with type 2 diabetes mellitus initiating SGLT2 versus dipeptidyl peptidase-4 inhibitors were created. The outcome was a composite of genital candidal infections, vaginitis or vulvovaginitis in women, and genital candidal infections, balanitis, balanoposthitis, phimosis or paraphimosis in men. Among propensity score-matched cohorts of 129 994 women and 156 074 men, the adjusted hazard ratio (HR) and excess risk per 1000 person-years for SGLT2 versus DPP-4 inhibitors was 2.81 (95% confidence interval [CI], 2.64, 2.99) and 87.4 (95% CI, 79.1, 96.2) respectively for women, and was 2.68 (95% CI, 2.31, 3.11) and 11.9 (95% CI, 9.3-15.0) for men. Findings were similar in the SGLT2 inhibitor versus GLP-1 agonist comparison, more pronounced in the subgroup of patients aged ≥60 (HR, 4.45 [95% CI, 3.83-5.17] in women and 3.30 [95% CI, 2.56-4.25] in men), and no meaningful difference across individual SGLT2 inhibitors was identified. This increase in risk was evident in the first month of treatment initiation and remained elevated throughout the course of therapy. SGLT2 inhibitors were associated with an approximately 3-fold increase in risk of genital infections.     

Incidence of cardiovascular disease in older Americans: the cardiovascular health study

OBJECTIVES: To estimate incidence rates of major cardiovascular disease (CVD) in older Americans. DESIGN: Longitudinal cohort study using prospectively collected data on cardiovascular events. SETTING: Four U.S. communities in the Cardiovascular Health Study (CHS). PARTICIPANTS: Five thousand eight hundred eighty-eight participants in CHS, aged 65 or older at enrollment, including 3,393 women (581 African American) and 2,495 men (343 African American). MEASUREMENTS: At semiannual contacts, participants reported any occurrence of clinical CVD. Medical records were obtained and adjudicated to confirm diagnosis of CVD. RESULTS: During 10 years of follow-up, incidence of coronary heart disease (CHD) per 1,000 person-years was 39.6 (95% confidence interval (CI)=36.4-43.1) in men and 22.3 (95% CI=20.4-24.2) in women. Cumulative event rates for CHD and myocardial infarction for women aged 75 and older at baseline were similar to those for men aged 65 to 74. The overall incidence of stroke was similar for men and women (14.7 (95% CI=13.0-16.6) and 13.7 (95% CI=12.4-15.1) per 1,000 person-years, respectively), but the risk of stroke increased with age more rapidly in women, resulting in a greater cumulative event rate for stroke in women than in men aged 75 and older. The incidence of congestive heart failure increased 9% with each year of age over 65 and was greater than 6% per year in Caucasian men and women aged 85 and older at baseline. Rates were similar in African Americans and Caucasians. CONCLUSION: The occurrence of new CVD in older Americans is high, indicating that preventive efforts need to be maintained into older ages.     

Anxiety characteristics independently and prospectively predict myocardial infarction in men the unique contribution of anxiety among psychologic factors.

OBJECTIVES: This study investigated whether anxiety characteristics independently predicted the onset of myocardial infarction (MI) over an average of 12.4 years and whether this relationship was independent of other psychologic variables and risk factors. BACKGROUND: Although several psychosocial factors have been associated with risk for MI, anxiety has not been examined extensively. Earlier studies also rarely addressed whether the association between a psychologic variable and MI was specific and independent of other psychosocial correlates. METHODS: Participants were 735 older men (mean age 60 years) without a history of coronary disease or diabetes at baseline from the Normative Aging Study. Anxiety characteristics were assessed with 4 scales (psychasthenia, social introversion, phobia, and manifest anxiety) and an overall anxiety factor derived from these scales. RESULTS: Anxiety characteristics independently and prospectively predicted MI incidence after controlling for age, education, marital status, fasting glucose, body mass index, high-density lipoprotein cholesterol, and systolic blood pressure in proportional hazards models. The adjusted relative risk (95% confidence interval [CI]) of MI associated with each standard deviation increase in anxiety variable was 1.37 (95% CI 1.12 to 1.68) for psychasthenia, 1.31 (95% CI 1.05 to 1.63) for social introversion, 1.36 (95% CI 1.10 to 1.68) for phobia, 1.42 (95% CI 1.14 to 1.76) for manifest anxiety, and 1.43 (95% CI 1.17 to 1.75) for overall anxiety. These relationships remained significant after further adjusting for health behaviors (drinking, smoking, and caloric intake), medications for hypertension, high cholesterol, and diabetes during follow-up and additional psychologic variables (depression, type A behavior, hostility, anger, and negative emotion). CONCLUSIONS: Anxiety-prone dispositions appear to be a robust and independent risk factor of MI among older men.     

Incident stroke after discharge from the hospital with a diagnosis of atrial fibrillation

PURPOSE: Atrial fibrillation is an important risk factor for stroke. We analyzed stroke risk over time in patients discharged from the hospital with a diagnosis of incident atrial fibrillation as compared with the risk of stroke in the Danish population. SUBJECTS AND METHODS: In a random sample of half of the Danish population, we identified 13,625 men and 13,577 women, aged 50 to 89 years, with a hospital diagnosis of atrial fibrillation and no prior diagnosis of stroke during 1980 to 1993. Data on other medical conditions were also available from 1977 to 1993, but medication data were not available. Patients were followed from the diagnosis of atrial fibrillation until the first diagnosis of stroke (nonfatal or fatal cerebral ischemic infarct and cerebral hemorrhage), death, or the end of 1993. The risk of stroke in these patients was compared with the risk in the Danish population using Poisson regression modeling to estimate relative risks (RR) and 95% confidence intervals (CI). RESULTS: For men with atrial fibrillation, the stroke rates increased by age, from 13 per 1,000 person-years in those ages 50 to 59 years, to 22 per 1,000 person-years in those ages 60 to 69 years, to 42 per 1,000 person-years in those ages 70 to 79 years, to 51 per 1,000 person-years in those ages 80 to 89 years. Age-specific stroke rates were similar in women with atrial fibrillation. Patients with a hospital diagnosis of atrial fibrillation had an increased risk of stroke (RR = 2.4; 95% CI, 2.3 to 2.5 in men and RR = 3.0; 95% CI, 2.9 to 3.2 in women) compared with the Danish population. Stroke risk was greatest during the first year after discharge and decreased thereafter. Hypertension, diabetes, and peripheral atherosclerosis were also associated with an increased risk of stroke among patients with atrial fibrillation. Ischemic heart disease and heart failure were risk factors in men only. There was no reduction in the risk of stroke from 1980 to 1993. CONCLUSIONS: Men and women with atrial fibrillation are at a substantially increased risk of stroke, particularly in the first year after the diagnosis.     

Relation of increased leptin concentrations to history of myocardial infarction and stroke in the United States population

Leptin, an adipose tissue-derived hormone, has been linked to cardiovascular outcomes; however, data are limited in the United States population, especially women. To assess the association between leptin concentrations and history of myocardial infarction (MI) and stroke independently of traditional cardiovascular risk factors, we analyzed data from 6,239 subjects (mean age 47 years; 3,336 women) with measurements of serum leptin and full assessment of cardiovascular risk factors from the National Health and Nutrition Examination Survey (NHANES) III. Logistic regression was used to estimate the cross-sectional association of leptin concentrations (highest quartile versus lowest quartile) and history of MI, stroke, and the composite end point of MI or stroke (MI/stroke). Gender-specific models of leptin were adjusted for age, race, dyslipidemia, hypertension, diabetes, smoking, and obesity status. There were 212 men with MI/stroke (5.4%), 154 with MI (4.1%), and 82 with stroke (1.7%). There were 135 women with MI/stroke (2.6%), 74 with MI (1.5%), and 78 with stroke (1.4%). In multivariate analysis, high leptin level was significantly and independently associated with MI/stroke in men (odds ratio [OR] 2.41, 95% confidence interval [CI] 1.20 to 4.93) and women (OR 4.26, 95% CI 1.75 to 10.73); with MI in men (OR 3.16, 95% CI 1.40 to 7.37) and women (OR 3.96, 95% CI 1.29 to 12.72), and with stroke in women (OR 3.20, 95% CI 1.04 to 10.54) but not in men (OR 1.37, 95% CI 0.38 to 3.88). In conclusion, in the United States population, increased leptin concentrations are significantly associated with MI/stroke in men and women independently of traditional cardiovascular risk factors and obesity status.     

Sex differences in the effect of diabetes duration on coronary heart disease mortality

BACKGROUND: It is not known whether the coronary heart disease (CHD) mortality risk associated with recent (RDM; <10 years) or long-standing diabetes mellitus (LDM; > or =10 years) varies by sex. METHODS: The relationship between diabetes duration and CHD mortality was evaluated among 10 871 adults (aged 35-74 years at baseline) using the 1971-1992 National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. RESULTS: The CHD mortality rates per 1000 person-years in men with no myocardial infarction (MI) or diabetes, MI only, RDM only, LDM only, MI and RDM, and MI and LDM were 5.5 (95% confidence interval, 4.8-6.2), 15.2 (11.6-20.0), 13.2 (7.9-22.1), 11.4 (6.4-20.3), 36.0 (16.7-77.7), and 35.4 (14.0-89.7), respectively. The corresponding rates in women were 2.9 (2.5-3.3), 7.3 (5.0-10.8), 5.2 (3.5-7.7), 10.7 (7.5-15.5), 9.3 (4.3-19.9), and 21.6 (6.1-76.0), respectively. Compared with MI, the multivariate hazard ratios and their 95% confidence intervals (adjusted for age, race, smoking, hypertension, total cholesterol level, and body mass index) for fatal CHD in men with RDM, LDM, MI and RDM, and MI and LDM were 0.7 (0.3-1.3), 0.8 (0.4-1.4), 3.2 (1.4-7.4), and 2.4 (0.8-6.7), respectively. The corresponding ratios in women were 0.9 (0.6-1.3), 1.8 (1.1-3.2), 1.3 (0.5-3.5), and 1.6 (0.2-10.9), respectively. CONCLUSIONS: In men, RDM and LDM were associated with as high a risk for CHD death as MI. In women, although RDM had a CHD mortality risk similar to MI, LDM had an even greater risk. Because women with LDM are at very high risk for CHD mortality, current guidelines may need to be further refined to match intensity of treatment to risk in these women.     

The risk of myocardial infarction is enhanced by a synergistic interaction between serum insulin and smoking

OBJECTIVES: To evaluate the relationship between levels of serum insulin, the homeostasis model assessment (HOMA) and IGF-binding protein-1 (IGFBP-1) as factors related to myocardial infarction (MI) risk, and their interaction with lifestyle-related risk factors. DESIGN: The Stockholm epidemiology programme (SHEEP), a case-control study, consisting of 749 first-time MI cases (510 men, 239 women) and 1101 healthy controls (705 men, 396 women) was used. METHODS: The risk of developing MI was assessed by calculating odds ratios (OR) and synergistic interactions (SI) between serum insulin, IGFBP-1, HOMA and other variables related to MI risk (including smoking) in men and women. RESULTS: Subjects with elevated levels of insulin and HOMA (>75th percentile) had increased MI risks when compared with individuals with low levels. ORs for elevated insulin and HOMA (adjusted for age and residential area) for men: insulin 1.6 (95% confidence interval (CI) 1.3-2.1) and HOMA 1.5 (95% CI 1.1-1.9) and for women: insulin 2.1 (95% CI 1.5-2.9) and HOMA 1.9 (95% CI 1.3-2.8). Women with low levels of IGFBP-1 (<10th percentile) showed a tendency towards elevated MI risk even if this was not statistically significant (OR 1.5 (95% CI 0.9-2.6)). Smokers with high levels of serum insulin had greatly increased MI risk (OR for men: 4.7 (95% CI 3.0-7.2) and OR for women: 8.1 (95% CI 4.5-14.8)). SI scores based upon these interactions were statistically significant. CONCLUSIONS: These results might have preventive cardiovascular implications as they clearly suggest that subjects with insulin resistance are particularly susceptible to the hazards of smoking.     

Usefulness of fasting blood glucose to predict vascular outcomes among individuals without diabetes mellitus (from the Northern Manhattan Study)

It is still controversial whether fasting blood glucose (FBG) is associated with the risk of vascular outcomes among nondiabetic subjects. We sought to determine whether FBG is associated with vascular outcomes and whether this association differs among various racial or ethnic groups. In the Northern Manhattan Study, a total of 2,372 subjects (mean age 68.8 +/- 10.7 years, 36% men) without a history of diabetes mellitus, stroke, or myocardial infarction (MI) were followed for an average of 7.5 years for ischemic stroke, MI, and combined vascular events defined as either ischemic stroke, MI, or vascular death. Cox proportional-hazards models were used to calculate hazard ratios and 95% confidence intervals (CIs) of FBG-associated risk for vascular outcomes after adjusting for age, gender, race/ethnicity, education, body mass index, hypertension, current smoking, previous coronary artery disease, low-density lipoprotein cholesterol, alcohol intake, and physical activity. The incidences of MI, ischemic stroke, and combined vascular events were 5.5, 6.3, and 20.0 per 1,000 person-years, respectively. Each SD increase of FBG (27 mg/dl) was associated with statistically significantly increased risks of combined vascular events (hazard ratio 1.20, 95% CI 1.09 to 1.31) and MI (hazard ratio 1.21, 95% CI 1.02 to 1.44), but the effect was weaker, evident for ischemic stroke (hazard ratio 1.13, 95% CI 0.95 to 1.34). FBG was significantly associated with incident ischemic stroke among African-American subjects (hazard ratio 1.38, 95% CI 1.09 to 1.74) and incident MI among Hispanic subjects (hazard ratio 1.24, 95% CI 0.99 to 1.55). In conclusion, FBG was an independent predictor for vascular outcomes among individuals without history of diabetes from this multiethnic cohort. The effects were more apparent for MI than for ischemic stroke; however, FBG was a strong predictor of ischemic stroke among African-American subjects.     

Lack of excess maternal transmission of type 2 diabetes in a Korean population

The purpose of this study was to assess the familial clustering of type 2 diabetes and to investigate the presence of excess maternal transmission of type 2 diabetes in Korea. The medical records of 56,492 subjects (31,680 men and 24,812 women), who attended the Health Promotion Center were examined. The subjects were questioned about their parents' diabetes status. All study subjects were classified into the three groups (normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetes). Offspring with paternal diabetes (odds ratio 2.54, 95% CI 2.22-2.91, P < 0.001) and those with maternal diabetes (odds ratio 3.10, 95% CI 2.76-3.49, P < 0.001) were at increased risk for diabetes when compared to subjects without parental diabetes and adjusted for other clinical and biochemical variables. Offspring with bilineal parental diabetes were at a greater risk for diabetes (odds ratio 6.09, 95% CI 4.55-8.16, P < 0.001) when compared to subjects without parental diabetes. In both genders, offspring with maternal diabetes showed no increased risk for diabetes (odds ratio 1.22, 95% CI 0.92-1.37, P + 0.266 in men; odds ratio 1.31, 95% CI 0.95-1.81, P = 0.104 in women) when compared with those with paternal diabetes. The data suggested that parental type 2 diabetes was an independent risk factor for offspring type 2 diabetes in this Korean population. Excess maternal transmission of type 2 diabetes was not observed.