Men Hazard Ratio Research Articles

Early loss to follow-up and mortality of HIV-infected patients diagnosed after the era of antiretroviral treatment scale up: a call for re-invigorating the response in Iran

In Iran, the HIV/AIDS epidemic is growing during an era of scaling up the national surveillance system and antiretroviral therapy programs. We examined the early loss to follow-up and mortality rates in a retrospective cohort of 1495 HIV-infected patients by survival proportional hazard Cox model. We also conducted a data abstraction sub-study in a systematic random sample of 147 patients to assess the association between mortality and predictor factors. Overall, 17.3% patients were not seen after their first visit and 17.4% more were lost by 6 months. The overall mortality rate was 7.0 (95% CI 6.1-8.1) per 100 person-years. Moreover, crude mortality rate was higher in men (8.6) than in women (1.7), with an age-adjusted hazard ratio for men compared to women of 4.55 (95% CI 2.31-8.93). Lastly, history of tuberculosis and not being on antiretroviral therapy were significantly associated with higher mortality in the patient sub-sample.

21st-Century Hazards of Smoking and Benefits of Cessation in the United States

Jha, Prabhat*; Ramasundarahettige, Chinthanie*; Landsman, Victoria*; Rostron, Brain†; Thun, Michael‡; Anderson, Robert N.§; Mcafee, Tim∥; Peto, Richard¶ Author Information

Impact of Hip Fracture on Mortality: A Cohort Study in Hip Fracture Discordant Identical Twins

Several studies have shown a long-lasting higher mortality after hip fracture, but the reasons for the excess risk are not well understood. We aimed to determine whether a higher mortality after hip fracture exists when controlling for genetic constitution, shared environment, comorbidity, and lifestyle by use of a nationwide cohort study in hip fracture discordant monozygotic twins. All 286 identical Swedish twin pairs discordant for hip fracture (1972 to 2010) were identified. Comorbidity and lifestyle information was retrieved by registers and questionnaire information. We used intrapair Cox regression to compute multivariable-adjusted hazard ratios (HRs) for death. During follow-up, 143 twins with a hip fracture died (50%) compared with 101 twins (35%) without a hip fracture. Through the first year after hip fracture, the rate of death increased fourfold in women (HR = 3.71; 95% confidence interval [CI] 1.32-10.40) and sevenfold in men (HR = 6.67; 95% CI 1.47-30.13). The increased rate in women only persisted during the first year after hip fracture (HR after 1 year = 0.99; 95% CI 0.66-1.50), whereas the corresponding HR in men was 2.58 (95% CI 1.02-6.62). The higher risk in men after the hip fracture event was successively attenuated during follow-up. After 5 years, the hazard ratio in men with a hip fracture was 1.19 (95% CI 0.29-4.90). On average, the hip fracture contributed to 0.9 years of life lost in women (95% CI 0.06-1.7) and 2.7 years in men (95% CI 1.7-3.7). The potential years of life lost associated with the hip fracture was especially pronounced in older men (>75 years), with an average loss of 47% (95% CI 31-61) of the expected remaining lifetime. We conclude that both women and men display a higher mortality after hip fracture independent of genes, comorbidity, and lifestyle.

Resting Heart Rate and the Risk of Heart Failure in Healthy Adults

Background— An elevated resting heart rate is associated with rehospitalization for heart failure and is a modifiable risk factor in heart failure patients. We aimed to examine the association between resting heart rate and incident heart failure in a population-based cohort study of healthy adults without pre-existing overt heart disease. Methods and Results— We studied 4768 men and women aged ≥55 years from the population-based Rotterdam Study. We excluded participants with prevalent heart failure, coronary heart disease, pacemaker, atrial fibrillation, atrioventricular block, and those using β-blockers or calcium channel blockers. We used extended Cox models allowing for time-dependent variation of resting heart rate along follow-up. During a median of 14.6 years of follow-up, 656 participants developed heart failure. The risk of heart failure was higher in men with higher resting heart rate. For each increment of 10 beats per minute, the multivariable adjusted hazard ratios in men were 1.16 (95% confidence interval, 1.05–1.28; P =0.005) in the time-fixed heart rate model and 1.13 (95% confidence interval, 1.02–1.25; P =0.017) in the time-dependent heart rate model. The association could not be demonstrated in women ( P for interaction=0.004). Censoring participants for incident coronary heart disease or using time-dependent models to account for the use of β-blockers or calcium channel blockers during follow-up did not alter the results. Conclusions— Baseline or persistent higher resting heart rate is an independent risk factor for the development of heart failure in healthy older men in the general population.

21st-Century Hazards of Smoking and Benefits of Cessation in the United States

BackgroundExtrapolation from studies in the 1980s suggests that smoking causes 25% of deaths among women and men 35 to 69 years of age in the United States. Nationally representative measurements of the current risks of smoking and the benefits of cessation at various ages are unavailable.MethodsWe obtained smoking and smoking-cessation histories from 113,752 women and 88,496 men 25 years of age or older who were interviewed between 1997 and 2004 in the U.S. National Health Interview Survey and related these data to the causes of deaths that occurred by December 31, 2006 (8236 deaths in women and 7479 in men). Hazard ratios for death among current smokers, as compared with those who had never smoked, were adjusted for age, educational level, adiposity, and alcohol consumption.ResultsFor participants who were 25 to 79 years of age, the rate of death from any cause among current smokers was about three times that among those who had never smoked (hazard ratio for women, 3.0; 99% confidence interval [CI], 2.7 to 3.3; hazard ratio for men, 2.8; 99% CI, 2.4 to 3.1). Most of the excess mortality among smokers was due to neoplastic, vascular, respiratory, and other diseases that can be caused by smoking. The probability of surviving from 25 to 79 years of age was about twice as great in those who had never smoked as in current smokers (70% vs. 38% among women and 61% vs. 26% among men). Life expectancy was shortened by more than 10 years among the current smokers, as compared with those who had never smoked. Adults who had quit smoking at 25 to 34, 35 to 44, or 45 to 54 years of age gained about 10, 9, and 6 years of life, respectively, as compared with those who continued to smoke.ConclusionsSmokers lose at least one decade of life expectancy, as compared with those who have never smoked. Cessation before the age of 40 years reduces the risk of death associated with continued smoking by about 90%.

Work and health among immigrants and native Swedes 1990–2008: a register-based study on hospitalization for common potentially work-related disorders, disability pension and mortality

BackgroundThere are many immigrants in the Swedish workforce, but knowledge of their general and work-related health is limited. The aim of this register-based study was to explore whether documented migrant residents in Sweden have a different health status regarding receipt of a disability pension, mortality and hospitalization for lung, heart, psychiatric, and musculoskeletal disorders compared with the native population, and if there were variations in relation to sex, geographical origin, position on the labor market, and time since first immigration.MethodsThis study included migrants to Sweden since 1960 who were 28–47 years old in 1990, and included 243 860 individuals. The comparison group comprised a random sample of 859 653 native Swedes. These cohorts were followed from 1991 to 2008 in national registers. The immigrants were divided into four groups based on geographic origin. Hazard ratios for men and women from different geographic origins and with different employment status were analyzed separately for the six outcomes, with adjustment for age, education level, and income. The influence of length of residence in Sweden was analyzed separately.ResultsNordic immigrants had increased risks for all investigated outcomes while most other groups had equal or lower risks for those outcomes than the Swedes. The lowest HRs were found in the EU 15+ group (from western Europe, North America, Australia and New Zealand). All groups, except Nordic immigrants, had lower risk of mortality, but all had higher risk of disability pension receipt compared with native Swedes. Unemployed non-Nordic men displayed equal or lower HRs for most outcomes, except disability pension receipt, compared with unemployed Swedish men. A longer time since first immigration improved the health status of men, while women showed opposite results.ConclusionsEmployment status and length of residence are important factors for health. The contradictory results of low mortality and high disability pension risks need more attention. There is great potential to increase the knowledge in this field in Sweden, because of the high quality registers.

Participation, characteristics and retention rates of HIV‐positive immigrants in the Swiss HIV Cohort Study*

Data from observational cohorts may be influenced by population structure and loss to follow-up (LTFU). Quality of care may be associated with participation in cohort networks. We aimed to study the participation, characteristics and retention rates of immigrants in the Swiss HIV Cohort Study (SHCS). We compared enrolment over time (1996-1999, 2000-2003 and 2004-2008) and LTFU between individuals from different geographical regions. In 2008, we performed a cross-sectional survey to investigate the proportion of individuals not participating in the SHCS but who were in care at SHCS institutions. Predictors for LTFU were analysed using Cox proportional hazard models, and those for nonparticipation using logistic regression. A total of 7840 individuals entered the SHCS during the observation period. The proportion of immigrants increased over time, especially the proportion of women from sub-Saharan Africa, which increased from 21 to 48% during the observation period. Overall LTFU was 3.76 [95% confidence interval (CI) 3.58-3.95]/100, with the highest hazard ratio in men from sub-Saharan Africa (2.82/100 patient-years; 95% CI 2.30-3.46/100), compared with men from northwestern countries. Other predictors for LTFU were age <30 years, lower education, injecting drug use, and higher baseline CD4 cell counts. Participants taking antiretroviral therapy had reduced LTFU. The survey showed that 84% of HIV-infected patients in care at SHCS institutions were enrolled in the cohort. Nonparticipation was more likely among men from non-European regions (odds ratio 2.73; 95% CI 2.29-3.24), women from sub-Saharan Africa (odds ratio 3.01; 95% CI 2.40-3.77) and women from Latin America/Caribbean (odds ratio 2.10; 95% CI 1.30-3.39). Numbers of HIV-infected immigrants are increasing but they are underrepresented in the SHCS, and immigrants are more likely to be lost to follow-up.

Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population. A total of 7,579 women and 6,372 men from the Copenhagen City Heart Study with measurements of nonfasting triglycerides and cholesterol at baseline in 1976-1978 were followed for up to 33 years; of these, 837 women and 837 men developed ischemic stroke during follow-up, which was 100% complete. The fluctuation of nonfasting triglycerides and cholesterol over 15 years was similar. In both women and men, stepwise increasing levels of nonfasting triglycerides were associated with increased risk of ischemic stroke. Compared to women with triglycerides <1 mmol/liter, multivariate adjusted hazard ratios ranged from 1.2 (95% confidence interval [CI], 0.9-1.7) for triglyceride levels of 1.00-1.99 mmol/liter to 3.9 (95%CI, 1.3-11.1) for triglyceride levels ≥ 5 mmol/liter (trend: p < 0.001); corresponding hazard ratios in men ranged from 1.2 (95%CI, 0.8-1.7) to 2.3 (95%CI, 1.2-4.3) (p = 0.001). Increasing cholesterol levels were not associated with risk of ischemic stroke except in men with cholesterol levels ≥ 9.00 mmol/liter vs < 5.00 mmol/liter, with a hazard ratio of 4.4 (95%CI, 1.9-10.6). In women, stepwise increasing levels of nonfasting triglycerides were associated with increasing risk of ischemic stroke while increasing cholesterol levels were not. In men, these results were similar except that cholesterol ≥ 9.00 mmol/liter was associated with increased risk of ischemic stroke.

Nonfasting cholesterol and triglycerides and association with risk of myocardial infarction and total mortality: the Copenhagen City Heart Study with 31 years of follow-up

We compared the ability of very high levels of nonfasting cholesterol and triglycerides to predict risk of myocardial infarction and total mortality. Prospective study from 1976 to 1978 until 2007. Danish general population. Randomly selected population of 7581 women and 6391 men, of whom 768 and 1151 developed myocardial infarction and 4398 and 4416 died, respectively. Participation rate was 72%, and follow-up was 100% complete. Less than 2% of participants were taking lipid-lowering therapy. Compared to women with cholesterol <5 mmol L(-1) , multivariate-adjusted hazard ratios for myocardial infarction ranged from 1.3 [95% confidence interval (CI): 0.9-1.8] for a cholesterol level of 5.0-5.99 mmol L(-1) to 2.5 (95%CI: 1.6-4.0) for cholesterol ≥ 9 mmol L(-1) (trend: P < 0.0001). Compared with women with nonfasting triglycerides <1 mmol L(-1) , hazard ratios for myocardial infarction ranged from 1.5 (95%CI: 1.2-1.8) for triglycerides of 1.0-1.99 mmol L(-1) to 4.2 (95%CI: 2.5-7.2) for triglycerides ≥ 5 mmol L(-1) (p<0.0001). In men, corresponding hazard ratios ranged from 1.2 (95%CI: 1.0-1.5) to 5.3 (95%CI: 3.6-8.0) for cholesterol (P < 0.0001) and from 1.3 (95%CI: 1.0-1.6) to 2.1 (95%CI: 1.5-2.8) for triglycerides (P < 0.0001). Increasing cholesterol levels were not consistently associated with total mortality in women (trend: P = 0.39) or men (P = 0.02). By contrast, compared with women with triglycerides <1 mmol L(-1) , multivariate-adjusted hazard ratios for total mortality ranged from 1.1 (95%CI: 1.0-1.2) for triglycerides of 1.0-1.99 mmol L(-1) to 2.0 (95%CI: 1.5-2.9) for triglycerides ≥5 mmol L(-1) (trend: P < 0.0001); corresponding hazard ratios in men ranged from 1.1 (95%CI: 1.0-1.2) to 1.5 (95%CI: 1.2-1.7) (P < 0.0001). Stepwise increasing levels of nonfasting cholesterol and nonfasting triglycerides were similarly associated with stepwise increasing risk of myocardial infarction, with nonfasting triglycerides being the best predictor in women and nonfasting cholesterol the best predictor in men. Even more surprisingly, only increasing levels of nonfasting triglycerides were associated with total mortality, whereas increasing cholesterol levels were not.

Progression Rate From New-Onset Pre-Hypertension to Hypertension in Korean Adults

There are limited studies conducted in Asia to investigate the progression rate to hypertension (HTN). This study was done to estimate the progression rate of new-onset pre-HTN (PreHTN) to HTN during an 8-year follow-up period, and to compare the impact of PreHTN on progression to HTN. A total of 49,228 participants, aged 30 to 54 years with new-onset PreHTN at baseline (1994-1996) from a biennial national medical exam were enrolled and followed up every 2 years until 2004. The incidence rate recorded at each interval and the cumulative incidence rate of HTN were analyzed. Hazard ratio of high-normal and high blood pressure (BP) in men and women was calculated. The cumulative incidence rate for high-normal BP was 27.6% and 26.4% at 2-year follow-up, increased to respectively 64.1% and 55.8% in men and women at the 8-year follow-up. Compared to optimal BP, hazard ratios for men with high-normal BP across all age groups were 3- to 4-fold higher at 2-year, and 2- to 3-fold higher at 8-year follow-up. Hazard ratios for women were about 6-fold higher at 2-year and around 4-fold higher at 8-year follow-up. New PreHTN was a significant predisposing factor for future HTN, in young adults and the effect is more prominent in women.

Measures of overweight and obesity and risk of cardiovascular disease: a population-based study

Although overweight and obesity are associated with cardiovascular disease (CVD), it is unclear which clinical measure of overweight and obesity is the strongest predictor of CVD, and it is unclear whether the various measures of overweight and obesity are indeed independent predictors of CVD. This study was a prospective population-based study of 2493 Danish men and women, age 41-72 years, without major CVD at baseline. At baseline, body mass index, waist circumference, hip circumference, waist-to-hip ratio (WHR), and traditional and new risk factors were recorded. Over a median follow-up of 12.6 years, the incidence of a combined CV event (CV death, nonfatal ischemic heart disease, and nonfatal stroke) amounted to 328 cases. Of the various measures of overweight and obesity, in Cox-proportional hazard models, adjusted for age, only WHR was significantly associated with incident CVD with a hazard ratio (95% confidence interval) in women of 2.22 (1.31-3.77; P=0.0032) in the highest compared with the lowest quartile, and a hazard ratio in men of 1.73 (1.12-2.66; P=0.014) in the highest compared with the lowest quartile. However, when adjustments were made for the presence of diabetes, dyslipidemia, hypertension, hyperinsulinemia, and inflammation, WHR was no longer significantly (P>0.41) associated with incident CVD. In this study, of the various measures of overweight and obesity, WHR was the only significant predictor of incident CVD, and the relationship between WHR and risk of CVD was mediated by well-known risk factors of CVD.

The Association Between Cancer Risk and Age at Onset of Smoking in Japanese

BackgroundYoung age at onset of smoking is a known risk factor for cancer; however, few studies have investigated the risk of cancer associated with onset of smoking during adolescence in Japan.MethodsWe analyzed a portion of the data from a population-based cohort of 40 897 subjects aged 40 to 69 years with a history of smoking and no history of cancer at baseline.ResultsDuring a 14-year follow-up period, 4386 total cancers and 681 lung cancers were newly diagnosed. As compared with smokers who started smoking after the age of 20 years, those who started before the age of 17 years smoked a significantly larger number of cigarettes per day for a significantly longer duration; they also had a significantly higher risk of lung cancer. The hazard ratios in men and women were 1.48 (95% confidence interval, 1.11–1.96) and 8.07 (2.34–27.85), respectively. After further adjustment for smoking amount, the associations remained significant. There was a statistically significant inverse correlation between lung cancer risk and age at onset of smoking in male current smokers whose baseline age was 50 to 59 years; no such association was detected among other age strata.ConclusionsThere was no clear evidence of increased risk of cancer due to adolescent smoking. However, adolescent smoking appeared to indirectly increase lung cancer risk because it was associated with a longer duration and larger amount of smoking.

Low Serum Bilirubin Level as an Independent Predictor of Stroke Incidence

Bilirubin is not only a waste end-product but also an antioxidant. Bilirubin is known to be associated with decrease in cardiovascular risk in men, but its relationship to stroke was not clearly understood. Serum bilirubin concentrations were measured in 78 724 health examinees (41 054 men, aged 30-89 years) from 1994 to 2001. The subjects with potential hepatobiliary diseases or Gilbert syndrome were excluded from analysis. Stroke incidence outcome was collected from hospital records of admission attributable to stroke from 1994 to 2007. Serum bilirubin measurements were divided into 4 levels: 0 to 10.2, 10.3 to 15.3, 15.4 to 22.1, and 22.2 to 34.2 micromol/L. The number of stroke cases was 1137 in men and 827 in women. In Cox proportional hazard models, participants with a higher level of bilirubin showed lower hazard ratios in men with ischemic stroke after adjustment for multiple confounding factors compared to the lowest level of bilirubin (hazard ratio [HR], 0.72; 95% CI, 0.58-0.90 in level 3; HR, 0.66; 95% CI, 0.49-0.89 in level 4; P for trend=0.016). The risk of all stroke types also decreased as bilirubin levels increased (HR, 0.81; 95% CI, 0.68-0.97 in level 3; HR, 0.74; 95% CI, 0.58-0.94 in level 4; P for trend=0.0071). However, these associations were not seen in hemorrhagic stroke or in women. These findings suggest that serum bilirubin might have some protective function against stroke risk in men.

Diabetes Patients Requiring Glucose-Lowering Therapy and Nondiabetics With a Prior Myocardial Infarction Carry the Same Cardiovascular Risk

Previous studies reveal major differences in the estimated cardiovascular risk in diabetes mellitus, including uncertainty about the risk in young patients. Therefore, large studies of well-defined populations are needed. All residents in Denmark > or = 30 years of age were followed up for 5 years (1997 to 2002) by individual-level linkage of nationwide registers. Diabetes patients receiving glucose-lowering medications and nondiabetics with and without a prior myocardial infarction were compared. At baseline, 71 801 (2.2%) had diabetes mellitus and 79 575 (2.4%) had a prior myocardial infarction. Regardless of age, age-adjusted Cox proportional-hazard ratios for cardiovascular death were 2.42 (95% confidence interval [CI], 2.35 to 2.49) in men with diabetes mellitus without a prior myocardial infarction and 2.44 (95% CI, 2.39 to 2.49) in nondiabetic men with a prior myocardial infarction (P=0.60), with nondiabetics without a prior myocardial infarction as the reference. Results for women were 2.45 (95% CI, 2.38 to 2.51) and 2.62 (95% CI, 2.55 to 2.69) (P=0.001), respectively. For the composite of myocardial infarction, stroke, and cardiovascular death, the hazard ratios in men with diabetes only were 2.32 (95% CI, 2.27 to 2.38) and 2.48 (95% CI, 2.43 to 2.54) in those with a prior myocardial infarction only (P=0.001). Results for women were 2.48 (95% CI, 2.43 to 2.54) and 2.71 (95% CI, 2.65 to 2.78) (P=0.001), respectively. Risks were similar for both diabetes types. Analyses with adjustments for comorbidity, socioeconomic status, and prophylactic medical treatment showed similar results, and propensity score-based matched-pair analyses supported these findings. Patients requiring glucose-lowering therapy who were > or = 30 years of age exhibited a cardiovascular risk comparable to nondiabetics with a prior myocardial infarction, regardless of sex and diabetes type. Therefore, requirement for glucose-lowering therapy should prompt intensive prophylactic treatment for cardiovascular diseases.

Relation of Adult-Onset Asthma to Coronary Heart Disease and Stroke

Asthma was associated with atherosclerotic disease in several studies, with evidence that this association may be limited to women. However, most previous studies failed to account for the heterogeneity of asthma subtypes. We previously reported increased carotid intima-medial thickness in women with adult-onset asthma. In this study, the association of adult- and child-onset asthma with incident coronary heart disease (CHD) and stroke were examined. Subjects were classified according to self-report of physician-diagnosed asthma and age of asthma onset. Cox proportional hazards models were used to test the association of adult- and child-onset asthma with incident CHD and stroke, testing for gender interaction. Subanalysis was also performed using only never smokers. Women with adult-onset asthma experienced a 2-fold increase in incident CHD and stroke that was independent of other risk factors, including smoking, body mass index, and physical activity, and persisted when analysis was restricted to never smokers. No significant association was found in women with child-onset asthma or in men. In conclusion, adult-onset asthma may be a significant risk factor for CHD and stroke in women, but not men.

Prostate Cancer-Specific Survival and Clinical Progression-Free Survival in Men with Prostate Cancer Treated Intermittently with Testosterone Inactivating Pharmaceuticals

More than 85% of men with prostate cancer die of other causes. An effective method is needed to distinguish fatal forms of prostate cancer from benign variants. We performed a retrospective chart review from a medical oncology practice specializing in prostate cancer. All men with negative bone scans, prostate-specific antigen (PSA) level less than 100 ng/mL, adequate records for review, and who started taking testosterone inactivating pharmaceutical (TIP) agents before January 2000 were included in the study. Six factors were evaluated as potential predictors of prostate cancer-specific mortality: PSA nadir greater than 0.05 ng/mL while taking TIP, PSA doubling time of less than 12 months, Gleason score, stage, baseline PSA level greater than 20 ng/mL, and age. The study criteria were met by 160 men. The median follow-up was 10 years. The median age, PSA level, PSA nadir, and PSA doubling time was 65.6 years, 9.6 ng/mL, 0.03 ng/mL, and 10 months, respectively. Of the 160 men, 39 died of prostate cancer. Death from prostate cancer was far more common (78% versus 11%) and accelerated (median of 4 years versus 7 years) for men with a PSA nadir greater than 0.05 ng/mL than for those with a lower nadir. Multivariate Cox regression analysis indicated that the hazard ratio for prostate cancer-specific mortality in men with a PSA nadir greater than 0.05 ng/mL was 11.6 (P <0.0001). The hazard ratio for men with a PSA doubling time of less than 12 months was 2.9 (P = 0.04). Gleason score, stage, baseline PSA level greater than 20 ng/mL, and age were not statistically significant. Of the factors studied, the PSA nadir while taking a TIP was the best predictor of prostate cancer-specific mortality.

Unrecognized myocardial infarction and the risk of stroke

To investigate the relationship between unrecognized myocardial infarction and the risk of stroke in a population-based cohort study. We followed 6,439 participants from the Rotterdam Study for stroke until January 2002. Participants were free from stroke, and presence of myocardial infarction was assessed at baseline (1990-1993). We calculated hazard ratios of stroke for persons with unrecognized or recognized myocardial infarction compared with persons without myocardial infarction. Analyses were adjusted for age, sex, and cardiovascular risk factors. In 52,915 person-years of follow-up, 505 strokes occurred. Recognized myocardial infarction was only borderline associated with an increased risk of stroke. Unrecognized myocardial infarction increased the risk of stroke by 76% (age- and sex-adjusted hazard ratio 1.76, 95% CI 1.31 to 2.37). Stratification by sex showed that the increased risk was only found in men (hazard ratio for men 2.53, 95% CI 1.68 to 3.81; hazard ratio for women 1.27, 95% CI 0.82 to 1.96). After adjusting for cardiovascular risk factors at baseline, the risk remained significantly increased in men (hazard ratio for stroke 2.13, 95% CI 1.35 to 3.36). Subtyping of strokes revealed that unrecognized myocardial infarction was particularly associated with cortical ischemic strokes (hazard ratio for men 3.57, 95% CI 1.79 to 7.12). Men with unrecognized myocardial infarction have an increased risk of stroke.

Combined Cardiovascular Risk Factors and Outcome

To examine the prognostic significance of the high-risk group with combined cardiovascular risk factors in the Japanese, we analyzed the relationship between the high-risk group with combined risks and coronary heart disease (CHD) and stroke mortality using the NIPPON DATA80 database. At baseline in 1980, those of age>or=30 years were randomly selected and 4,144 men and 5,318 women without CHD and/or stroke at baseline were followed for 14 years. The cutoff values for risk components obtained heuristically by Cox analysis were hypertension (systolic>or=130, or diastolic>or=85 mmHg, or on antihypertensive drugs), hypercholesterolemia (total cholesterol>or=200 mg/dl), hyperglycemia (>or=130 mg/dl, or self-reported diabetes) and obesity (body mass index>or=27 kg/m2). Subjects were divided into 3 groups (0, 1-2 and 3-4 risks). Compared with those men in the risk 0 group, the hazard ratios in men in the risk 3-4 for CHD mortality was 8.04 (95% confidence interval: 1.03-62.6), and the stroke mortality was 5.06 (1.53-16.7). In women, no statistically significant difference was found due to a lesser number of events. The high-risk group with combined risk factors is important risk for Japanese men.

The Effect of Gender on Outcome in Digitalis-Treated Heart Failure Patients

Background The use of digitalis is recommended for the treatment of heart failure to reduce hospitalization. Recent data suggest that digitalis treatment may adversely affect survival in women but not in men. We studied patients with left ventricular dysfunction enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) to determine whether there was a gender-based survival difference in patients treated with digitalis. Methods and Results Symptomatic (n = 2569) and asymptomatic (n = 4228) patients with left ventricular ejection fraction ≤0.35 were studied. Digitalis use was assessed at baseline and baseline demographic variables were catalogued and compared. A multivariate analysis, incorporating known covariates of risk for adverse cardiovascular events, was used to examine the association of digitalis with all-cause mortality, cardiovascular death, death from heart failure, and arrhythmic death, with, or without, worsening heart failure in women compared with men. Analysis for an interaction between digitalis and gender on mortality was also performed. No interaction between gender and digitalis treatment on survival was found, and there was no significant difference in the hazard ratios for men and women on digitalis either with respect to all-cause mortality, cardiovascular mortality, heart failure mortality, or arrhythmic death with worsening heart failure. When mortality for arrhythmic death without worsening heart failure was adjusted for the probability of being treated with digitalis (propensity analysis), women fared better than men. Conclusion Data from the SOLVD trials suggest that digitalis treatment of heart failure does not result in a difference in survival between men and women. Because a randomized trial to definitively answer the question is unlikely, and perhaps inappropriate, examination of other heart failure populations for a gender-digitalis interaction is indicated.

Sleep disturbance as a predictor of type 2 diabetes mellitus in men and women from the general population

To examine gender specific associations between sleep disturbance and incident type 2 diabetes mellitus in a representative population sample in Germany. The study was based on 4,140 men and 4,129 women (aged 25-74 years) who participated in one of the three MONICA Augsburg surveys between 1984 and 1995, and who were free of diabetes at baseline. Incident cases of type 2 diabetes were assessed using a follow-up questionnaire in 1998. Gender specific hazard ratios were estimated from Cox proportional hazard models. A total of 119 cases of incident type 2 diabetes among men and 69 among women were registered during the mean follow-up period of 7.5 years. In both sexes, difficulty maintaining sleep was associated with a higher risk of type 2 diabetes. After adjustment for age, survey, hypertension, dyslipidemia, parental history of diabetes, history of angina pectoris, regular smoking, physical activity, alcohol intake, body mass index and education, the hazard ratio in men was 1.60 (95% CI: 1.05-2.45) and the hazard ratio in women was 1.98 (95% CI: 1.20-3.29). In contrast, difficulty initiating sleep was not associated with a significantly increased risk of developing type 2 diabetes mellitus after multivariable adjustment in both sexes in the present study. Difficulty maintaining sleep was associated with an increased risk of type 2 diabetes in men and women from the general population. Although, the causal pathway is not entirely clear, it seems that both insulin resistance and chronic low-grade systemic inflammation may be involved.