Relationship Between Higher Estradiol Levels and 9-Year Mortality in Older Women: The Invecchiare in Chianti Study

OBJECTIVES: To investigate the relationship between total estradiol (E2) levels and 9-year mortality in older postmenopausal women not taking hormone replacement therapy (HRT).
DESIGN: Population-based study of persons living in the Chianti geographic area (Tuscany, Italy).
SETTING: Community.
PARTICIPANTS: A representative sample of 509 women aged 65 and older with measures of total E2.
MEASUREMENTS: Serum total E2 was measured at the University of Parma using ultrasensitive radioimmunoassay (RIA).
RESULTS: Women who died (n=135) during 9 years of follow up were older; had higher total E2 levels; and were more likely to have evidence of stroke, hypertension, diabetes mellitus, and congestive heart failure at baseline than survivors. Higher E2 levels were associated with a greater likelihood of death (hazard ratio (HR)=1.03, 95% confidence interval (CI)=1.01–1.06), and the relationship was independent of age, waist:hip ratio, C-reactive protein, education, cognitive function, physical activity, caloric intake, smoking, and chronic disease (HR=1.08 pg/mL, 95% CI=1.03–1.13, P =.003). The excessive risk of death associated with higher total E2 was not attenuated after adjustment for total testosterone (HR=1.12, 95% CI=1.02–1.18, P <.001) and after further adjustment for insulin resistance evaluated using the homeostasis model assessment (HR=1.07, 95% CI=1.03–1.17, P <.001).
Total E2 was highly predictive of death after more than 5 years (HR=1.42: CI 1.01–1.91, P =.04) and not predictive of death for less than 5 years ( P =.78).
CONCLUSION: Higher total E2 concentration predicts mortality in older women not taking HRT.     

Association between aortic calcification and total and cardiovascular mortality in older women

OBJECTIVES: To determine whether older women with abdominal aortic calcification had a greater cardiovascular and all-cause mortality, as such data are limited in older adults. DESIGN: Prospective cohort study with a mean follow-up of 13 years. SETTING: Community-based sample with four US clinical centres. SUBJECTS: A total of 2056 women aged > or =65 years with abdominal aortic calcification assessed on baseline radiographs. MAIN OUTCOME MEASURE: Mortality rate (all, cardiovascular, cancer or other cause) adjudicated from death certificates and hospital records. RESULTS: The prevalence of abdominal aortic calcification increased with age, ranging from 60% at age 65-69 years to 96% at 85 years and older. Participants with aortic calcification were more likely to die during follow-up of any cause (47% vs. 27%) or a cardiovascular-specific cause (18% vs. 11%, both P < 0.001) than those without aortic calcification. In age-adjusted analyses, aortic calcification was associated with a greater rate of all-cause and cause-specific mortality (cardiovascular, cancer, and other, all P < or = 0.01). In analyses adjusted for age and cardiovascular risk factors, aortic calcification was associated with an increased rate of all-cause mortality (HR: 1.37, 95% CI: 1.15-1.64), and noncardiovascular noncancer mortality (HR: 1.57, 95% CI: 1.17-2.11). The associations between aortic calcification and cancer mortality (HR: 1.44, 95% CI: 1.00-2.08) or cardiovascular mortality (HR: 1.18, 95% CI: 0.88-1.57) showed a similar pattern without reaching statistical significance, but was slightly stronger for mortality from coronary heart disease (HR: 1.53, 95% CI: 0.91-2.56). CONCLUSIONS: Abdominal aortic calcification in older women is associated with increased mortality. Future research should examine potential mechanisms for this association.     

The relationship between weight loss and all-cause mortality in older men and women with and without diabetes mellitus: the Rancho Bernardo study

OBJECTIVES: To examine the relationship between measured weight change over an approximate 10-year time period on all-cause mortality over the following 12 years in 1,801 community-dwelling men and women (mean age 71 at the beginning of mortality follow-up) with and without diabetes mellitus. DESIGN: A longitudinal cohort study. SETTING: A geographically defined community in southern California. PARTICIPANTS: One thousand eight hundred one older men and women with and without diabetes mellitus. MEASUREMENTS: Weight, body mass index (BMI), blood pressure, and fasting plasma glucose were measured in 1972-74 (Visit 1) when participants were aged 40 to 79 and again in 1984-87 (Visit 2). Lifetime weight history and dieting for weight control were ascertained in 1985 using a mailed questionnaire. Vital status was determined for the next 12 years, from Visit 2 (1984-87) through 1996. The Cox proportional hazards model was used to assess the age- and multiply adjusted effect of weight change on mortality. RESULTS: At Visit 1, diabetic men (n = 140) and women (n = 90) were more overweight than nondiabetic men (n = 633) and women (n = 938). Weight gain between Visits 1 and 2 was not a significant predictor of mortality in this cohort. Men and women losing 10 or more pounds between visits had higher age-adjusted death rates during the following 12 years than those with stable weight or weight gain. Weight loss was associated with an increased hazard ratio (HR) for all-cause mortality in nondiabetic men (HR = 1.38, 95% confidence interval (CI) = 1.06-1.80) and women (HR = 1.76, 95% CI = 1.33-2.34) and diabetic men (HR = 3.66, 95% CI = 2.15-6.24) and women (HR = 1.65, 95% CI = 0.70-3.87) after adjustment for age, smoking, and sedentary lifestyle. Significant associations persisted in analyses excluding cigarette smokers and those with depressed mood and low baseline BMI. After excluding those who died within 5 years of the weight loss, the increased HR was statistically significant in men and women with and without diabetes mellitus. Stratified analyses comparing those who reported dieting for weight control with those not dieting showed similar trends, with a higher mortality risk for weight loss in those who lost weight without dieting. CONCLUSION: In this population of older individuals, weight loss predicted increased all-cause mortality risk not explained by covariates.     

Mortality among veterans with type 2 diabetes initiating metformin, sulfonylurea or rosiglitazone monotherapy

Aims/hypotheses

Despite oral hypoglycaemic medications being the most commonly used pharmacological treatments for type 2 diabetes, research is limited on their comparative safety, particularly their effects on overall mortality. We compared mortality risk with monotherapy initiation of four oral hypoglycaemic medications in a nationwide cohort of US veterans with type 2 diabetes.

Methods

We identified new users of oral hypoglycaemic medication monotherapy between 2004 and 2009 who received care for at least 1 year from the Veterans Health Administration. Patients were followed until initial monotherapy discontinuation, addition of another diabetes pharmacotherapy, death or end of follow-up. Mortality HRs were estimated using Cox regression adjusted for potential confounding factors.

Results

Among new users of metformin, sulfonylureas and rosiglitazone (185,360 men, 7,812 women), 4,256 (2.2%) died during follow-up. Average duration of medication use ranged from 1.4 to 1.7 years. Significantly higher mortality risk was seen for glibenclamide (known as glyburide in the USA and Canada) (HR 1.38, 95% CI 1.27, 1.50) or glipizide (HR 1.55, 95% CI 1.43, 1.67) compared with metformin monotherapy, and for glipizide compared with rosiglitazone (HR 1.27, 95% CI 1.01, 1.59) or glibenclamide monotherapy (HR 1.12, 95% CI 1.02, 1.23). A significant sex–rosiglitazone interaction was seen (p?=?0.034) compared with metformin monotherapy, with women having a higher HR (HR 4.36, 95% CI 1.34, 14.20) than men (HR 1.19, 95% CI 0.95, 1.49).

Conclusions/interpretations

Significantly higher mortality was associated with glibenclamide, glipizide and rosiglitazone use compared with metformin, and with glipizide use compared with rosiglitazone or glibenclamide. The potential for residual confounding by indication should be considered in interpreting these results.     

Correlates and outcomes of preserved left ventricular systolic function among older adults hospitalized with heart failure

Background Heart failure (HF) in older adults is often associated with preserved left ventricular systolic function (LVSF). The objective of this retrospective follow-up study was to determine the correlates and outcomes of preserved LVSF among older adults hospitalized with HF. Methods We studied older Medicare beneficiaries hospitalized with HF (n = 1091) who had documented LVSF evaluation (n = 438). LVSF was defined as preserved if left ventricular ejection fraction was ≥40%. The Fisher exact test and the Student t test were used to compare baseline characteristics between patients with preserved versus those with impaired LVSF. Multivariate logistic regression analysis was used to determine the correlates of preserved LVSF. Cox proportional hazards analyses were used to determine the associations between LVSF and both 4-year mortality rates and 6-month readmission rates and the associations between angiotensin-converting enzyme (ACE) inhibitor use and 4-year mortality rates, separately, in patients with preserved and impaired LVSF. Results Of the 438 patients, 200 (46%) had preserved LVSF. Women were more likely to have preserved LVSF (odds ratio [OR] = 2.44, 95% CI 1.57-3.81) than men. Preserved LVSF was associated with lower 4-year mortality rates (adjusted hazards ratio [HR] = 0.67, 95% CI 0.52-0.86) but not with 6-month readmission rates (adjusted HR = 0.66, 95% CI 0.41-1.09). The use of ACE inhibitors was associated with lower 4-year mortality rates in patients with impaired LVSF (adjusted HR = 0.61, 95% CI 0.43-0.86) but not in those with preserved LVSF (HR = 0.96, 95% CI 0.65-1.42). Conclusions Among older adults hospitalized with HF, preserved LVSF was common among women and was associated with significantly higher morbidity and mortality rates, which were unaffected by treatment with ACE inhibitors. (Am Heart J 2002;144:365-72.)     

Low femoral bone mineral density and quantitative ultrasound are risk factors for new osteoporotic fracture and total and cardiovascular mortality: a 5-year population-based study of Brazilian elderly women

BACKGROUND: Prospective and cross-sectional studies have confirmed a significant association between bone mineral density (BMD) measurements and fracture risk. However, the relationship among incident fracture risk, mortality, BMD, and quantitative ultrasound is controversial and less studied. METHODS: At baseline, 275 postmenopausal elderly women were evaluated by clinical questionnaire regarding fracture risk factors and had radiological analysis of the spine, spine and femur dual energy x-ray absorptiometry, and calcaneous quantitative ultrasound measurements. Five years later, 42 (15.3%) women had died, 25 (9.1%) were lost to follow-up, and 208 (75.6%) continued the study. Specific questionnaire items regarding fracture risk were reevaluated, and thoracic and lumbar spine x-rays were taken to identify new fractures. Causes of mortality in this population were also assessed. All reported deaths were confirmed by review of death certificates or hospital records and were classified according to International Classification of Diseases, 10th Revision (ICD-10) code. RESULTS: After adjustments for age, weight, body mass index, smoking status, previous fracture, physical activity, drug use, and presence of chronic diseases, each 1 standard deviation (SD) reduction in stiffness index (SI) at baseline was significantly associated with future fracture (hazard ratio [HR] = 2.23; 95% confidence interval [CI], 1.30-3.83) and total mortality 5 years later (HR = 1.57; 95% CI, 1.10-2.47). Femoral neck and trochanter BMD values at baseline were also related to new fracture (HR = 2.01; 95% CI, 1.27-3.18 and HR = 1.62; 95% CI, 1.08-2.42, respectively) and total mortality (HR = 1.44; 95% CI, 1.06-2.22 and HR = 1.59; 95% CI, 1.07-2.36, respectively). Cardiovascular mortality was associated with decreased baseline femur BMD (HR = 1.28; 95% CI, 1.08-2.26) and lower SI values (HR = 1.54; 95% CI, 1.08-2.79). CONCLUSIONS: Our results demonstrate that low femoral BMD and low SI are able to predict fracture risk and are related to non-cause-specific and cardiovascular mortality, independently of other factors associated with osteoporosis, death, or aging.     

The Mid-term Mortality and Mode of Death in Survivors with ST-elevation Myocardial Infarction

Objective The popularity of primary percutaneous coronary intervention (p-PCI) for ST-elevation myocardial infarction (STEMI) has increased over the past decades. Despite improvements in in-hospital mortality rates, it is clinically important to investigate the prognoses after discharge. However, data on the mode of death and prognostic factors are limited. We analyzed these factors in a Japanese cohort in the modern p-PCI era. Methods Between January 2004 and December 2017, a total of 1,222 patients who underwent p-PCI within 24 hours from the onset of STEMI and were alive at discharge (mean age, 67.7 years old; men, 75.5%), were evaluated. The two-year mortality was analyzed using a Cox regression model, and the mode of death was evaluated. Results The rate of mortality at 2 years was 5.7%. Non-cardiac death was more frequent than cardiac death (62.6% vs. 37.4%). A Cox multivariate analysis identified the following as independent predictors of the 2-year mortality: hemoglobin (log-transformed) [adjusted hazard ratio (HR), 0.048; 95% confidence interval (CI), 0.008-0.29; p<0.001], age above 80 years old (adjusted HR, 2.26; 95% CI, 1.30-3.91; p=0.004), Killip class ≥II (adjusted HR, 1.99; 95% CI, 1.17-3.39; p=0.011), brain natriuretic peptide level (log-transformed) (adjusted HR, 1.47; 95% CI, 1.09-2.01; p=0.013), and body mass index (log-transformed) (adjusted HR, 0.16; 95% CI, 0.030-0.84; p=0.030). Conclusion This study demonstrated that the 2-year mortality was 5.7% in STEMI survivors after p-PCI. Non-cardiac death was more frequent than cardiac death. Compared to well-known clinical variables, angiographic findings did not have a significant influence on the mid-term mortality.     

Risk factors for death among patients in French Guiana: 1996-2005

Risk factors for death in an HIV-infected cohort in French Guiana were studied in 1374 patients between 1996 and 2005. Of these patients, 48.5% were male and 76% were immigrants. Covariates were measured at the time of consultation. There were 223 deaths. Addictions [adjusted hazard ratio (HR)=13; 95% confidence interval (CI) 5.5-30.6; P<0.001], age>60 years (HR=1.5; 95% CI 0.9-2.5; P=0.13), male gender (HR=1.5; 95% CI 1.03-2.5; P=0.03) and CD4 count<50 cells/microL (HR=9.1; 95% CI 5.1-16.3; P<0.001) were independently associated with death. These results suggest that strategies promoting early diagnosis and better follow-up of addicted patients would have a significant impact on mortality.     

Statin use and survival outcomes in elderly patients with heart failure

BACKGROUND: Coronary artery disease is a leading cause of heart failure. Statins are efficacious drugs for the primary and secondary prevention of coronary heart disease, but their value in persons with heart failure remains unknown. METHODS: We performed a population-based retrospective cohort study involving the entire province of Ontario, Canada, restricting participants to those aged 66 to 85 years who were free of cancer and who survived at least 90 days following hospitalization for newly diagnosed heart failure. The primary study outcome was the risk of death from all causes, nonfatal acute myocardial infarction, or nonfatal stroke among persons newly dispensed statins (n = 1,146) relative to those who were not (n = 27,682). RESULTS: The mean age of all participants was 76.5 years, and half were women. During the 7-year study period, death, acute myocardial infarction, or stroke occurred in 217 statin recipients (13.6 per 100 person-years) vs 12,299 nonrecipients (21.8 per 100 person-years; adjusted hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.83). Most of the benefit from statins was related to a reduction in all-cause mortality (adjusted HR, 0.67; 95% CI, 0.57-0.78). No significant reduction was seen for subsequent myocardial infarction (adjusted HR, 0.81; 95% CI, 0.63-1.03) or stroke (adjusted HR, 0.81; 95% CI, 0.53-1.25). CONCLUSIONS: Statin use is associated with a lower risk of death among seniors newly diagnosed as having congestive heart failure. While statin use has been previously shown to be efficacious in patients with coronary heart disease and stroke, we could not control for all prognostic risk factors in the present study, including left ventricular ejection fraction and serum lipid levels. Better evidence can direct clinicians about which patients with heart failure might benefit from these drugs.     

Plasma renin and risk of cardiovascular disease and mortality: the Framingham Heart Study.

AIMS: Previous studies relating plasma renin to cardiovascular disease (CVD) and mortality yielded conflicting results. We related plasma renin to incidence of CVD and mortality in 3408 individuals (mean age 59; 53% women) and in a hypertensive subset (n = 1413). METHODS AND RESULTS: On follow-up (mean 7.1 years), 176 participants (122 hypertensives) developed CVD and 215 individuals (127 hypertensives) died. Overall, log-renin was associated with mortality [multivariable-adjusted hazards ratio (HR) per SD increment: in whole sample, 1.14, 95% confidence interval (CI) 1.00-1.30, P = 0.046; hypertensives, 1.16, 95% CI 1.00-1.35, P = 0.046], but relations varied over time (P < 0.02). Log-renin was associated with mortality at 2.5 years of follow-up (HR per SD increment: whole sample at 2.5 years, 1.23, 95% CI 1.04-1.45; hypertensives at 2 years, 1.28, 95% CI 1.06-1.54), but not during longer follow-up (HR per SD increment at 5 years: whole sample, 1.02, 95% CI 0.80-1.29; hypertensives, 0.98, 95% CI 0.74-1.30). The time-dependent relation of renin and mortality risk was maintained upon excluding participants with prevalent CVD. Renin was not associated with CVD incidence (HR per SD increment log-renin: whole sample, 0.99, 95% CI 0.85-1.14; hypertensives, 0.96, 95% CI 0.82-1.12). CONCLUSION: Higher plasma renin was associated with greater short-term mortality but not with CVD incidence in the community.     

Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort

OBJECTIVE: To test the hypothesis that the C-reactive protein (CRP) concentration at baseline is an independent predictor of death from cardiovascular disease (CVD) in newly diagnosed patients with inflammatory polyarthritis (IP). METHODS: Patients with IP (n = 506) who were recruited from the Norfolk Arthritis Register between 1990 and 1992 were followed up to the end of 2001, and complete data on mortality were obtained. At baseline, subjects underwent a structured interview and joint examination and completed a Health Assessment Questionnaire (HAQ). Blood was obtained and analyzed for rheumatoid factor (RF) and CRP concentration. Cox regression was used to calculate hazards ratios (HRs) for risk of death from CVD. RESULTS: The median followup was 10.1 years (interquartile range 9.3-10.8). There were 104 deaths, 40 of which were the result of CVD. Elevated CRP levels (> or=5 mg/liter) predicted death from CVD in univariate analyses: HR 3.9 (95% confidence interval [95% CI] 1.2-13.4) for men, and HR 4.22 (95% CI 1.4-12.6) for women. After adjusting for age and sex, the CVD mortality association was strongest in the subgroup of patients who were RF positive at baseline (adjusted HR 7.4 [95% CI 1.7-32.2]). Multivariate analysis revealed that elevated CRP levels remained a significant independent predictor of death from CVD, even after adjusting for age, sex, smoking status, HAQ score, RF positivity, and swollen joint counts (HR 3.3 [95% CI 1.4-7.6]). CONCLUSION: The CRP concentration at baseline is an important predictor of subsequent death from CVD in patients with new-onset IP and is independent of other indicators of disease severity. This supports the theory that CRP may play a direct role in the pathogenesis of CVD.     

Effectiveness of adjuvant chemotherapy for node-positive operable breast cancer in older women

BACKGROUND: Randomized clinical trials have shown the efficacy of adjuvant chemotherapy in treating node-positive operable breast cancer in women aged < or = 69 years, but the benefit of chemotherapy in women aged > or = 70 is questionable. This study was to examine if adjuvant chemotherapy is effective for these women with breast cancer. METHODS: We studied a cohort of 5464 women diagnosed with node-positive operable breast cancer at age > or = 65 in 1992 through 1996 with last follow-up of December 31, 1999 in five states and six metropolitan areas. Hazard ratio (HR) for all-cause mortality was used for survival analysis with adjustment for patient and tumor characteristics; propensity analysis was used to control for observed factors; and sensitivity analysis was used to estimate potential effects of unmeasured confounders. RESULTS: After adjusting for propensity to receive chemotherapy, the chemotherapy-treated and untreated groups were not statistically significantly different for covariates except for age and hormone receptor status. Mortality was significantly reduced in women aged 65-69 who received adjuvant chemotherapy compared to those who did not, after adjusting for patient and tumor characteristics (HR = 0.70, 95% confidence interval [CI], 0.57-0.88) or after adjusting for propensity scores (HR = 0.76, 95% CI, 0.62-0.94). HR did not significantly differ between the treated and untreated women aged > or = 70 (HR = 0.96, 95% CI = 0.83-1.09, and HR = 0.99, 95% CI, 0.87-1.14). These results were relatively insensitive to changes in unmeasured confounders. CONCLUSIONS: Adjuvant chemotherapy is associated with improved survival in women with node-positive operable breast cancer aged 65-69 living in the community, but not in women aged > or = 70. These findings are consistent with those found in randomized controlled trials.     

Relevance of Target-Organ Lesions as Predictors of Mortality in Patients with Diabetes Mellitus

Background

Patients with diabetes are in extract higher risk for fatal cardiovascular events.

Objective

To evaluate major predictors of mortality in subjects with type 2 diabetes.

Methods

A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR) and confidence interval (CI) related to cardiovascular and total mortality.

Results

After 9.2 years of follow-up (median), 33 subjects died (17 from cardiovascular causes). Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019); prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007); eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001); long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004); and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002). Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030); smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046); prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005), and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017).

Conclusions

Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes.     

Pulse hypertension: a new component of the metabolic syndrome in elderly women?

The classification of arterial hypertension (HT) to define metabolic syndrome (MS) is unclear in that different cutoffs of blood pressure (BP) have been proposed. We evaluated the categorization of HT most qualified to define MS in relationship with coronary heart disease (CHD) mortality at a population level. A total of 3257 subjects aged > or =65 years were followed up for 12 years. MS was defined according to the criteria of the National Education Cholesterol Program using three different categories of HT: MS-1 (systolic blood pressure (SBP) > or =130 and diastolic blood pressure (DBP) > or =85 mm Hg), MS-2 (SBP > or =130 or DBP > or =85 mm Hg) and MS-3 (pulse pressure (PP) > or =75 mm Hg in men and > or =80 mm Hg in women). Gender-specific adjusted hazard ratio (HR) with 95% confidence intervals (CI) for CHD mortality was derived from Cox analysis in the three MS groups, both including and excluding antihypertensive treatment. In women with MS untreated for HT, the risk of CHD mortality was always significantly higher than in those without MS, independent of categorization; the HR of MS was 1.73 (CI 1.12-2.67) using MS-1, 1.75 (CI 1.10-2.83) using MS-2 and 2.39 (CI 3.71-1.31) using MS-3. In women with MS treated for HT, the HR of CHD mortality was significantly increased only in the MS-3 group (1.92, CI 1.1-2.88). MS did not predict CHD in men. In conclusion, MS can predict CHD mortality in elderly women with untreated HT but not in those with treated HT; in the latter, PP is the most predictive BP value.     

Cocaine and the Long-Term Risk of Cardiovascular Disease in Women

BackgroundCocaine is associated with acute cardiovascular complications, but the long-term cardiovascular risks of cocaine use are poorly understood. We examined the association between cocaine use disorders and long-term cardiovascular morbidity in women.MethodsWe analyzed a longitudinal cohort of 1,296,463 women in Quebec, Canada between 1989 and 2020. The exposure included cocaine use disorders prior to or during pregnancy. The outcome was cardiovascular hospitalization up to 31 years later. We used adjusted Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of cocaine use disorders with cardiovascular hospitalization.ResultsThe cohort included 2954 women with cocaine use disorders. Compared with women without an identified cocaine disorder, women with cocaine use disorders had 1.55 times greater risk of future cardiovascular hospitalization during 3 decades of follow-up (95% CI, 1.37-1.75). Cocaine use disorders were strongly associated with inflammatory heart disease (HR 4.82; 95% CI, 2.97-7.83), cardiac arrest (HR 2.93; 95% CI, 1.46-5.88), valve disease (HR 3.09; 95% CI, 2.11-4.51), and arterial embolism (HR 2.22; 95% CI, 1.19-4.14). The association between cocaine use disorder and cardiovascular hospitalization was most marked after 5 to 10 years of follow-up (HR 2.15; 95% CI, 1.70-2.72).ConclusionsWomen with cocaine use disorders have a high risk of cardiovascular hospitalization up to 3 decades later. Substance use reduction and cardiovascular risk surveillance may help reduce the burden of cardiovascular disease in women with cocaine use disorders.     

Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study

BACKGROUND: The prognostic significance of proteinuria in older people is not well defined. We examined the associations between proteinuria and incident coronary heart disease, cardiovascular mortality, and all-cause mortality in older people.SUBJECTS AND METHODS: Casual dipstick proteinuria was determined in 1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7 years) attending the 15th biennial examination of the Framingham Heart Study. Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%), and greater-than-trace (4.5%). Cox proportional hazards analyses were used to determine the relations of baseline proteinuria to the specified outcomes, adjusting for other risk factors, including serum creatinine level.RESULTS: During 17 years of follow-up, there were 455 coronary heart disease events, 412 cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4), and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7).CONCLUSION: Proteinuria is a significant, although relatively weak, risk factor for all-cause mortality in men and women, and for cardiovascular disease mortality in women.     

Renin-angiotensin system and nitric oxide synthase gene polymorphisms in relation to stroke

BACKGROUND: There is ample evidence that genetic factors contribute to cardiovascular disease risk. The present study aimed to assess the relation between polymorphisms of the angiotensin II type 1 receptor (AGTR1 A(1166)C) and endothelial nitric oxide synthase (NOS3 G(894)T) and the risk of stroke. METHODS: We performed a case-cohort study on all first fatal and nonfatal stroke events (n = 74) and a 10% random sample (n = 1523) of a population-based cohort of women aged 49 to 70 years (n = 15,236; median follow-up 4.3 years). Univariate and multivariate unweigthed Cox proportional hazards regression models were used to assess the relation between the polymorphisms, their interactions with coexisting risk factors, and the risk of stroke. RESULTS: The relation between the AGTR1 CC genotype and stroke risk (unadjusted hazards ratio [HR] 1.62; 95% confidence interval [CI], 0.81-3.28) was modified by increasing age (>56 years: adjusted HR 2.77; 95% CI, 1.17-6.56) and systolic blood pressure (BP) (>130 mm Hg: adjusted HR 2.58; 95% CI, 1.12-5.93). The NOS3 G(894)T polymorphism, however, was not associated with stroke risk. CONCLUSIONS: In the presence of other coexisting risk factors the AGTR1 A(1166)C but not the NOS3 G(894)T polymorphism increased the risk of stroke. The CC genotype may help identify those individuals who are at greatest risk and who may need (early) treatment or careful follow-up.     

Relation of heart rate parameters during exercise test to sudden death and all-cause mortality in asymptomatic men

Heart rate (HR) profile during exercise predicts all-cause mortality. However, less is known about its relation to sudden (vs nonsudden) death in asymptomatic people. The relation of exercise HR parameters (HR at rest, target HR achievement, HR increase, and HR recovery) with sudden death, coronary heart disease (CHD) death, myocardial infarction, and all-cause mortality was assessed in 12,555 men who participated in MRFIT. Subjects were 35 to 57 years old without clinical CHD, but with higher than average Framingham risk. Trial follow-up was 7 years, and extended follow-up after the trial for all-cause mortality was 25 years. After adjusting for cardiac risk factors, having to stop exercise before achieving 85% of age-specific maximal HR was associated with increased risk of sudden death (hazard ratio 1.8, 95% confidence interval [CI] 1.3 to 2.5, p = 0.001), CHD death (hazard ratio 1.4, 95% CI 1.2 to 1.5, p <0.001), and all-cause mortality (hazard ratio 1.3, 95% CI 1.2 to 1.4, p <0.001). Increased HR at rest (p = 0.001), attenuated HR increase (p = 0.02), delayed HR recovery (p = 0.04), and exercise duration (p <0.0001) were independent predictors of all-cause death in the overall study population and also in the subgroup that achieved target HR. In conclusion, middle-aged men without clinical CHD who stopped exercise before reaching 85% of maximal HR had a higher risk of sudden death. Other exercise HR parameters and exercise duration predicted all-cause mortality.     

Ethnic differences in cardiovascular and all-cause mortality in Birmingham, England: the Birmingham Factory Screening Project

OBJECTIVES: To compare cardiovascular and all-cause mortality, among white Europeans, African-Caribbeans and South-Asians, in relation to baseline demographic characteristics and blood pressure variables. DESIGN: Observational follow-up study. SETTING: Community settings in Birmingham, UK. PARTICIPANTS: Two thousand and eighty-nine white European and 340 African-Caribbean men and women, and 195 South-Asian men whose survival status on 31 December 2003 was known. INTERVENTIONS: Follow-up for assessment of all-cause and cardiovascular mortality over a mean (SD) 20.3 (4.2) years. MAIN OUTCOME MEASURES: All-cause and cardiovascular mortality. RESULTS: There were no significant ethnic differences in all-cause or cardiovascular mortality for men [adjusted hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.80-1.28 and HR = 1.33; 95% CI, 0.99-1.79, respectively] or women (adjusted HR = 0.61; 95% CI, 0.29-1.32 and HR = 1.19; 95% CI, 0.41-3.45, respectively) in either univariate or multivariate analyses. The only independent predictors of both all-cause and cardiovascular mortality were age, sex, smoking and mean systolic blood pressure or hypertension. CONCLUSIONS: It appears that ethnicity per se is not an independent risk factor for all-cause and cardiovascular mortality between white Europeans and African-Caribbeans in the present study. The data concerning ethnic differences in all-cause and cardiovascular mortality for South-Asians is limited, given that significantly fewer South-Asian men could be traced by the Office for National Statistics (ONS), hence we do not know their survival status, and the total lack of data on South-Asian women.     

Renal insufficiency as an independent predictor of mortality among women with heart failure

OBJECTIVES: We sought to explore the association between renal insufficiency and mortality among women with heart failure (HF) and to evaluate this risk by the presence of preserved or depressed systolic function. BACKGROUND: Although HF is common in older women, little is known about their risk factors for mortality. METHODS: This prospective cohort study retrospectively analyzed data from the Heart and Estrogen/progestin Replacement Study (HERS). Of the 2,763 women in HERS, 702 had HF. Renal function was categorized as creatinine clearance (CrCl) >60 ml/min, 40 to 60 ml/min, and <40 ml/min. We used proportional hazards models to evaluate the association between renal insufficiency and mortality. RESULTS: Over a mean 5.8 years, 228 women with HF died (32%). Renal insufficiency was strongly associated with mortality, even after adjustment for co-morbid conditions, systolic function, and medications (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.09 to 2.16 for CrCl 40 to 60 ml/min; adjusted HR 2.40, 95% CI 1.60 to 3.62 for CrCl <40 ml/min). Preserved or depressed systolic function did not modify the association between renal insufficiency and mortality risk, but the use of angiotensin-converting enzyme (ACE) inhibitors did modify this risk (ACE users: adjusted HR = 0.9, 95% CI 0.6 to 1.6; ACE nonusers: adjusted HR 2.1, 95% CI 1.3 to 3.2; p = 0.02 for interaction). Compared with other risk factors for mortality, renal insufficiency had the highest population attributable risk (27%). CONCLUSIONS: Renal insufficiency was a major predictor of mortality among women with HF and preserved or depressed systolic function. This risk was attenuated by the use of ACE inhibitors.