Biomedical subjects

Eric Vittinghoff

Publications and source records attributed to Eric Vittinghoff.

At least 73 records · Page 4Linked to original sources

PubMed2004

Reduced risk of inadequate prenatal care in the era after Medicaid expansions in California.

BACKGROUND: To improve perinatal outcomes in the United States, access to prenatal care was expanded through Medicaid and women were encouraged to enter prenatal care early. OBJECTIVE: The objective of this study was to determine if expanded eligibility for Medicaid increased use of prenatal care and reduced ethnic differences in use of prenatal care. RESEARCH DESIGN: We conducted secondary analysis of California birth certificate data for 1990, 1995, and 1998. SUBJECTS: We studied live-born singleton infants born to black, Asian, Latina, and white women (n = 1,483,951). MAIN OUTCOME MEASURES: Inadequate utilization of prenatal care. RESULTS: The proportion of live-born infants whose mothers had inadequate prenatal care decreased from 20% in 1990 to 14% in 1995 and 12% in 1998. In addition, the proportion of pregnant women with no insurance or who were self-paying fell from 13.1% in 1990 to 4.2% in 1995 and 3.6% in 1998 (P <0.001). Reductions in overall prevalence of inadequate use of prenatal care and ethnic disparities in use of prenatal care were not fully explained by increases in Medicaid coverage. CONCLUSIONS: Since California expanded access to Medicaid-funded prenatal care, there has been a substantial reduction in inadequate use of prenatal care and fewer women have no insurance or are self-paying. To further reduce ethnic disparities in use of health services, new policies must be developed to remove nonfinancial barriers to early and continuous use of prenatal care.

Adolescent↗

PubMed2003

Association of total and central obesity with mortality in postmenopausal women with coronary heart disease.

Overweight and abdominal obesity increase mortality risk, although the risk may be mediated by traditional cardiac risk factors. The authors assessed the association of baseline measures, change in overall body weight and abdominal obesity (waist circumference), and weight and waist circumference cycling with total mortality among postmenopausal women with known heart disease. They used data from 2,739 US women who participated in the Heart and Estrogen/progestin Replacement Study between 1993 and 2001. Over 6.8 years of follow-up, 498 women died. In adjusted Cox models that included either baseline waist circumference or body mass index (BMI), each was associated with mortality. However, after further adjustment for diabetes, hypertension, and lipoproteins, these associations disappeared. In models including both waist circumference and BMI, larger waist circumference (hazard ratio=1.40 per standard deviation, 95% confidence interval: 1.16, 1.68) was associated with increased risk and higher BMI (hazard ratio=0.81 per standard deviation, 95% confidence interval: 0.67, 0.97) was associated with decreased risk of total mortality, independent of cardiac risk factors. Weight and waist circumference cycling were not associated with mortality. Results show that both BMI and waist circumference are associated with mortality among postmenopausal women with established heart disease, but waist circumference may be more important than BMI, and their effects may be largely mediated by other cardiac risk factors.

Aged↗

PubMed2003

The -1030/-862-linked TNF promoter single-nucleotide polymorphisms are associated with the inability to control HIV-1 viremia.

Control of HIV-1 viremia and progression to AIDS has been associated with specific HLA genes. The tumor necrosis factor ( TNF) and the non-classical major histocompatibility (MHC) class I chain-related A ( MICA) genes are located in the genomic segment between the HLA class I and II genes and variants of both genes have been identified. We thus analyzed TNF promoter and MICA variants in a well-characterized group of HIV-1 infected individuals with different abilities to control HIV-1 viremia. In our cohort, the -1030/-862-linked TNF promoter single-nucleotide polymorphisms (SNPs), but not MICA variants, are significantly associated with lack of control of HIV-1 viremia ( P=0.03). This association is independent of those HLA-B35 alleles associated with HIV-1 disease progression with which the -862 TNF SNP has previously been independently associated. Thus, non-randomly associated genes near the TNF locus are likely involved in control of HIV-1 viremia.

HIV Infections↗

PubMed2003

Fracture and the risk of coronary events in women with heart disease.

BACKGROUND: Osteoporosis is associated with aortic calcification and cardiovascular mortality. However, whether skeletal fractures predict the risk of coronary events is unknown. METHODS: We used Cox proportional hazards models to determine whether postmenopausal fracture was associated with the risk of coronary heart disease events among the 2763 postmenopausal women with known coronary disease enrolled in the Heart and Estrogen/progestin Replacement Study. Because fractures occurred before enrollment (in 615 women) and during follow-up (in 276 women), we treated incident fracture as a time-dependent covariate in our models. RESULTS: During a mean follow-up of 4.1 years, 361 women had coronary heart disease events. The risk of these events was 25% lower in women who sustained fractures than in those without fractures (hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.57 to 0.96; P = 0.02). This association was not confounded by physical activity or by factors associated with both fracture and coronary heart disease events (HR = 0.75; 95% CI: 0.57 to 0.98; P = 0.04). CONCLUSION: Postmenopausal women with heart disease who had skeletal fractures had a reduced risk of subsequent coronary events. This unexpected association, if confirmed in future studies, could influence risk-related treatment strategies for cardiovascular disease.

Aged↗

PubMed2003

Risk factors and secondary prevention in women with heart disease: the Heart and Estrogen/progestin Replacement Study.

BACKGROUND: Risk factors for coronary heart disease events have most commonly been evaluated in healthy men. OBJECTIVE: To assess risk factors, event rates, and use of secondary prevention treatments in women with preexisting coronary disease. DESIGN: A prospective cohort of clinical trial participants. SETTING: 20 U.S. clinical centers. PARTICIPANTS: 2763 postmenopausal women with known coronary disease in the Heart and Estrogen/progestin Replacement Study (HERS). MEASUREMENTS: Myocardial infarction or death from coronary heart disease. RESULTS: On multivariable analysis, the researchers found 11 risk factors: 6 noted by history (nonwhite ethnicity, lack of exercise, treated diabetes, angina, congestive heart failure, and more than one previous myocardial infarction) and 5 that were measured (blood pressure, low-density lipoprotein cholesterol level, high-density lipoprotein cholesterol level, lipoprotein(a) level, and creatinine clearance). The annual rate of coronary events was 1.3% (95% CI, 0.7% to 2.5%) in women with no risk factors and 8.7% (CI, 7.1% to 10.8%) in women with five or more risk factors (a sixfold increase). At entry into HERS, 83% of participants were receiving aspirin or other antiplatelet agents, 33% were receiving beta-blockers, 18% were receiving angiotensin-converting enzyme inhibitors, and 53% were receiving lipid-lowering drugs. Women with more risk factors were less likely to be taking aspirin (P < 0.001) and lipid-lowering drugs (P = 0.006). CONCLUSIONS: Women with coronary disease are at high risk for myocardial infarction or death from coronary heart disease even in the absence of other risk factors, and their risk increases up to sixfold when many risk factors are present. Established drugs for secondary prevention, including aspirin, beta-blockers, and lipid-lowering agents, are underused in these women, especially those at highest risk.

Adrenergic beta-Antagonists↗

PubMed2003

Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Randomized trials of postmenopausal hormone therapy have found differing effects on fasting glucose levels. No trial has evaluated the effect of hormone therapy on diabetes incidence. OBJECTIVE: To evaluate the effect of hormone therapy on fasting glucose level and incident diabetes. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 20 U.S. clinical centers. PARTICIPANTS: 2763 postmenopausal women with coronary heart disease who were followed for 4.1 years. At baseline, 734 women had diabetes, 218 women had impaired fasting glucose, and 1811 women were normoglycemic; the 2029 women without diabetes were followed for incident diabetes. INTERVENTION: 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily, or placebo. MEASUREMENTS: Fasting glucose level was measured at baseline, at year 1, and at the end of the trial. Incident diabetes was defined by self-report of diabetes or disease complication, fasting glucose level of 6.9 mmol/L or greater (> or =126 mg/dL), or initiation of therapy with diabetes medication. RESULTS: Fasting glucose levels increased significantly among women assigned to placebo but did not change among women receiving hormone therapy. The incidence of diabetes was 6.2% in the hormone therapy group and 9.5% in the placebo group (relative hazard, 0.65 [95% CI, 0.48 to 0.89]; P = 0.006). The number needed to treat for benefit to prevent one case of diabetes was 30 (CI, 18 to 103). Changes in weight and waist circumference did not mediate this effect. CONCLUSIONS: In women with coronary disease, hormone therapy reduced the incidence of diabetes by 35%. This observation provides important insights into the metabolic effects of postmenopausal hormones but is insufficient to recommend the use of hormones for secondary prevention of heart disease.

Aged↗

PubMed2003

Lipid changes on hormone therapy and coronary heart disease events in the Heart and Estrogen/progestin Replacement Study (HERS).

BACKGROUND: Despite the effect of lowering low-density lipoprotein cholesterol (LDL-C) levels and raising high-density lipoprotein cholesterol (HDL-C) levels, combination hormone therapy did not reduce the incidence of coronary heart disease (CHD) events in the Heart and Estrogen/progestin Replacement Study (HERS). To explore possible mechanisms, we examined the association between lipid changes and CHD outcomes among women assigned to hormone therapy. METHODS: HERS participants were postmenopausal women with previously diagnosed CHD who were randomly assigned to receive conjugated estrogens and medroxyprogesterone or identical placebo and then followed-up for an average of 4.1 years. Among women assigned to hormone therapy, associations between baseline-to-year-1 lipid level changes and CHD events were compared with the associations observed for baseline lipids using multivariate proportional hazards models. RESULTS: Among women assigned to hormone therapy, CHD events were independently predicted by baseline LDL-C levels (relative hazard [RH] 0.94 per 15.6 mg/dL decrease, 95% CI 0.88-1.01) and HDL-C levels (RH 0.89 per 5.4 mg/dL increase, 95% CI 0.81-0.99), but not by triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.97-1.06). CHD events were marginally associated with first-year reductions in LDL-C levels (RH 0.95 per 15.6 mg/dL decrease, 95% CI 0.86-1.04), and were not associated with increases in HDL-C levels ( RH 1.03 per 5.4 mg/dL increase, 95% CI 0.91-1.16) or triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.98-1.05). CONCLUSION: Changes in lipid levels with hormone therapy are not predictive of CHD outcomes in women with heart disease in the HERS trial.

Aged↗

PubMed2003

Stress urinary incontinence surgery in the United States.

OBJECTIVE: To describe the prevalence, regional rates and demographic characteristics, morbidity, and mortality of stress urinary incontinence surgeries in the United States. METHODS: We used data from the 1998 National Hospital Discharge Survey and the 1998 National Census to calculate rates of surgeries for stress urinary incontinence by age, race, and region of the United States. From these data we estimated morbidity and mortality associated with incontinence surgery. RESULTS: In 1998, approximately 135000 women had inpatient surgery for stress urinary incontinence in the United States. The mean age of these women was 54.0 (+/-13.3) years. The South had the highest rate of surgery (14.8 per 10000 women), whereas the Northeast had the lowest (9.8 per 10000). In the 79% of discharges for which race was stated, the surgery rate for whites (11.6 per 10000) was almost five times greater than for blacks (2.6 per 10000), whereas the perioperative complication rate for blacks was twice that for whites (20.6% compared with 9.7%). Almost 70% of incontinence surgeries were done in combination with other major gynecologic procedures. For all incontinence surgeries, approximately 18% had complications, and mortality was rare (0.01%). CONCLUSION: Stress urinary incontinence surgery is common, especially among white women. Differences in regional and racial surgical rates may represent differences in physician practice, patient expectations, and access to or utilization of care.

Adult↗

PubMed2003

A randomized comparison of total or supracervical hysterectomy: surgical complications and clinical outcomes.

OBJECTIVE: To compare surgical complications and clinical outcomes after total versus supracervical abdominal hysterectomy for control of abnormal uterine bleeding, symptomatic uterine leiomyomata, or both. METHODS: We conducted a randomized intervention trial in four US clinical centers among 135 patients who had abdominal hysterectomy for symptomatic uterine leiomyomata, abnormal uterine bleeding refractory to hormonal treatment, or both. Patients were randomly assigned to receive a total or supracervical hysterectomy performed using the surgeon's customary technique. Using an intention-to-treat approach, we compared surgical complications and clinical outcomes for 2 years after randomization. RESULTS: Sixty-eight participants were assigned to supracervical hysterectomy (SCH) and 67 to total abdominal hysterectomy (TAH). Hysterectomy by either technique led to statistically significant reductions in most symptoms, including pelvic pain or pressure, back pain, urinary incontinence, and voiding dysfunction. Patients randomly assigned to (SCH) tended to have more hospital readmissions than those randomized to TAH, but this difference was not statistically significant. There were no statistically significant differences in the rate of complications, degree of symptom improvement, or activity limitation. Participants weighing more than 100 kg at study entry were twice as likely to be readmitted to the hospital during the 2-year follow-up period (relative risk [RR] 2.18, 95% confidence interval [CI] 1.06, 4.48, P=.034). CONCLUSION: We found no statistically significant differences between (SCH) and TAH in surgical complications and clinical outcomes during 2 years of follow-up.

Aged↗

PubMed2003

Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States.

Black Americans experience a disproportionate burden of ESRD compared with whites. Whether this is caused by the increased prevalence of chronic renal insufficiency (CRI) among blacks or by their increased progression from CRI to ESRD was investigated. A birth cohort analysis was performed using data from the Third National Health and Nutrition Examination Survey and the United States Renal Data System. It was assumed that those who developed ESRD in 1996 aged 25 to 79 yr came from the source population with CRI aged 20 to 74 yr that was sampled in the Third National Health and Nutrition Examination Survey (midpoint 1991). GFR was estimated using the Modification of Diet in Renal Disease study equation. The prevalence of CRI (GFR 15 to 59 ml/min per 1.73 m(2)) was not different among black compared with white adults (2060 versus 2520 per 100,000; P = 0.14). For each 100 blacks with CRI in 1991, five new cases of ESRD developed in 1996, whereas only one case of ESRD developed per 100 whites with CRI (risk ratio, 4.8; 95% confidence interval, 2.9 to 8.4). The increased risk for blacks compared with whites was only modestly affected by adjustment for age, gender, and diabetes. Blacks with CRI had higher systolic (147 versus 136 mmHg; P = 0.001) and diastolic (82 versus 77 mmHg; P = 0.02) BP and greater albuminuria (422 versus 158 micro g urine albumin/mg urine creatinine; P = 0.01). The higher incidence of ESRD among blacks is not due to a greater prevalence of CRI among blacks. The key to understanding black-white differences in ESRD incidence lies in understanding the extreme differences in their progression from CRI to ESRD.

Adult↗

PubMed2002

Hostility predicts recurrent events among postmenopausal women with coronary heart disease.

Psychosocial characteristics may be associated with an increased risk of coronary heart disease (CHD). Whether hostility predicts recurrent coronary events is unknown. A total of 792 women in the Heart and Estrogen/progestin Replacement Study (HERS) were evaluated prospectively to determine the role of hostility as a risk factor for secondary CHD events (nonfatal myocardial infarction and CHD death). The mean age of study participants was 67 years, and the average length of follow-up was 4.1 years. The study was conducted between 1993 and 1998, and all study sites were in the United States. High Cook-Medley hostility scores were associated with greater body mass index (p = 0.01) and higher levels of serum triglycerides (p = 0.05), and they were inversely associated with high density lipoprotein cholesterol (p = 0.04), self-rated general health (p < 0.001), age (p = 0.05), and education (p = 0.001). Compared with women in the lowest hostility score quartile, women in the highest quartile were twice as likely to have had a myocardial infarction (relative hazard = 2.03, 95% confidence interval: 1.02, 4.01). The relation between hostility and CHD events was not mediated or confounded by the biologic, behavioral, and social risk factors studied. In this study, hostility was found to be an independent risk factor for recurrent CHD events in postmenopausal women.

Aged↗

PubMed2002

Short-course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: a multicenter clinical trial.

BACKGROUND: Rifampin and pyrazinamide are recommended for treatment of latent tuberculosis infection in adults without HIV infection, but reports of severe hepatotoxicity have raised concerns about its safety. Clinical trials have not compared this treatment with isoniazid in adults without HIV infection. OBJECTIVE: To compare the safety and tolerance of a 2-month regimen of rifampin and pyrazinamide with that of a 6-month regimen of isoniazid for treatment of latent tuberculosis infection. DESIGN: Multicenter, prospective, open-label trial. SETTING: Three urban public health tuberculosis clinics in the United States. PATIENTS: 589 adults with latent tuberculosis infection who met U.S. criteria for treatment. INTERVENTION: Patients were assigned in alternate weeks to receive rifampin and pyrazinamide daily for 2 months (n = 307) or isoniazid daily for 6 months (n = 282). MEASUREMENTS: Primary end points were hepatotoxicity, other adverse events, and percentage of patients who completed treatment. RESULTS: Sixteen of 207 (7.7%) patients assigned to rifampin and pyrazinamide developed grade 3 or 4 hepatotoxicity compared with 2 of 204 (1%) patients assigned to isoniazid (odds ratio, 8.46 [95% CI, 1.9 to 76.5]; P = 0.001). The rifampin plus pyrazinamide regimen was more likely than the isoniazid regimen to be discontinued because of hepatotoxicity (odds ratio, 5.19; P = 0.033). The overall percentage of nonhepatotoxic adverse events was 20% in the rifampin-pyrazinamide group and 16% in the isoniazid group. The proportion of patients who completed the study treatment was 61% and 57%, respectively. CONCLUSIONS: A 2-month regimen of rifampin and pyrazinamide was associated with an increased risk for grade 3 or 4 hepatotoxicity compared with a 6-month regimen of isoniazid. Liver enzymes should be measured routinely during treatment to screen for liver injury and prevent progression to severe toxicity.

Adult↗

PubMed2002

Sexual risk behaviors and implications for secondary HIV transmission during and after HIV seroconversion.

OBJECTIVES: To determine the potential for secondary HIV transmission among newly HIV-infected men who have sex with men (MSM) during their HIV antibody seroconversion period, and for the 12 months after seroconversion. DESIGN: A cohort study. METHODS: Risk assessment questionnaires administered before receipt of the first positive HIV antibody result, plasma and seminal viral load measurements, and risk assessments one month and quarterly after receipt of the first HIV-positive test, and generalized estimating equation modelling techniques to analyse behavioral trends. RESULTS: Of 66 seroconverters, more than half reported unprotected anal intercourse (UAI) with HIV-negative or unknown-serostatus partners during seroconversion, with 27% reporting insertive UAI with an HIV-negative partner. The initial median plasma viral load was 4.6 log/ml, the median seminal viral load was 2.7 log/ml, suggesting a high level of infectiousness. Compared with risk behavior during seroconversion, UAI with HIV-negative or unknown-serostatus partners was reduced after the receipt of positive antibody results; however, a substantial proportion of participants reported high-risk behaviors for transmission for 12 months of follow-up. After learning of their HIV infection, recent seroconverters did not reduce the risk of secondary transmission by engaging in proportionally more high-risk practices with HIV-infected partners (compared with HIV-negative or unknown-serostatus partners), or engaging in proportionally more receptive compared with insertive UAI. CONCLUSION: Substantial potential exists for secondary HIV transmission during and for one year after HIV seroconversion. Receipt of an HIV-positive test is associated with a significant reduction in risk behavior, reinforcing the need to identify and counsel recently HIV-infected MSM.

Adult↗

PubMed2002

Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II).

CONTEXT: The Heart and Estrogen/progestin Replacement Study (HERS) found no overall reduction in risk of coronary heart disease (CHD) events among postmenopausal women with CHD. However, in the hormone group, findings did suggest a higher risk of CHD events during the first year, and a decreased risk during years 3 to 5. OBJECTIVE: To determine if the risk reduction observed in the later years of HERS persisted and resulted in an overall reduced risk of CHD events with additional years of follow-up. DESIGN AND SETTING: Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent unblinded follow-up for 2.7 years (HERS II) conducted at outpatient and community settings at 20 US clinical centers. PARTICIPANTS: A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II. INTERVENTION: Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate (n = 1380), or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II. The proportions with at least 80% adherence to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group, and increased from 0% (year 1) to 8% (year 6) in the placebo group. MAIN OUTCOME MEASURES: The primary outcome was nonfatal myocardial infarction and CHD death. Secondary cardiovascular events were coronary revascularization, hospitalization for unstable angina or congestive heart failure, nonfatal ventricular arrhythmia, sudden death, stroke or transient ischemic attack, and peripheral arterial disease. RESULTS: There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS, HERS II, or overall. The unadjusted relative hazard (RH) for CHD events in HERS was 0.99 (95% confidence interval [CI], 0.81-1.22); HERS II, 1.00 (95% CI, 0.77-1.29); and overall, 0.99 (0.84-1.17). The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups (RH, 0.97; 95% CI, 0.82-1.14), and in analyses restricted to women who were adherent to randomized treatment assignment (RH, 0.96; 95% CI, 0.77-1.19). CONCLUSIONS: Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular events in women with CHD. Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD.

Aged↗

PubMed2002

Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II).

CONTEXT: The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized trial of estrogen plus progestin therapy after menopause. OBJECTIVE: To examine the effect of long-term postmenopausal hormone therapy on common noncardiovascular disease outcomes. DESIGN AND SETTING: Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent open-label observational follow-up for 2.7 years (HERS II), carried out between 1993 and 2000 in outpatient and community settings at 20 US clinical centers. PARTICIPANTS: A total of 2763 postmenopausal women with coronary disease and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II. INTERVENTION: Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II. The proportions with at least 80% adherence to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group and increased from 0% (year 1) to 8% (year 6) in the placebo group. MAIN OUTCOME MEASURES: Thromboembolic events, biliary tract surgery, cancer, fracture, and total mortality. RESULTS: Comparing women assigned to hormone therapy with those assigned to placebo, the unadjusted intention-to-treat relative hazard (RH) for venous thromboembolism declined from 2.66 (95% confidence interval [CI], 1.41-5.04) during HERS to 1.40 (95% CI, 0.64-3.05) during HERS II (P for time trend =.08); it was 2.08 overall for the 6.8 years (95% CI, 1.28-3.40), and 3 of the 73 women with thromboembolism died within 30 days due to pulmonary embolism. The overall RH for biliary tract surgery was 1.48 (95% CI, 1.12-1.95); for any cancer, 1.19 (95% CI, 0.95-1.50); and for any fracture, 1.04 (95% CI, 0.87-1.25). There were 261 deaths among those assigned to hormone therapy and 239 among those assigned to placebo (RH, 1.10; 95% CI, 0.92-1.31). Adjusted and as-treated analyses did not alter our conclusions. CONCLUSIONS: Treatment for 6.8 years with estrogen plus progestin in older women with coronary disease increased the rates of venous thromboembolism and biliary tract surgery. Trends in other disease outcomes were not favorable and should be assessed in larger trials and in broader populations.

Aged↗

PubMed2002

Statin therapy, cardiovascular events, and total mortality in the Heart and Estrogen/Progestin Replacement Study (HERS).

BACKGROUND: Although effects of statins on cardiovascular outcomes are well established in men, fewer data exist for women. Furthermore, the effects of statins plus hormone replacement therapy (HRT) on cardiovascular outcomes are uncertain. METHODS AND RESULTS: We examined statin use, cardiovascular events, and total mortality in the Heart and Estrogen/progestin Replacement Study (HERS), a randomized clinical trial of estrogen plus progestin versus placebo in postmenopausal women with heart disease (n=2763). A nonrandomized comparison of statin users and nonusers revealed lower rates of the primary outcome, nonfatal myocardial infarction or coronary heart disease death (relative hazard [RH]=0.79, 95% confidence intervals [CI] 0.63 to 0.99, P=0.04), and total mortality (RH=0.67, 95% CI 0.51 to 0.87, P=0.003). Rates of venous thromboembolic events were also lower among statin users (RH=0.45, 95% CI 0.23 to 0.88, P=0.02). HRT resulted in a significant increase in early risk for primary events in women who did not use statins (RH=1.75, 95% CI 1.02 to 3.03, P=0.04) but not in statin users (RH=1.34, 95% CI 0.63 to 2.86, P=0.45). Adjustment for postrandomization statin use showed no effect of HRT on risk for the primary outcome (RH=0.96, 95% CI 0.77 to 1.29; P=0.72). CONCLUSIONS: In HERS, statin use was associated with lower rates of cardiovascular events, venous thromboembolic events, and total mortality. These data provide strong support for statin use in eligible women with coronary disease.

Aged↗

PubMed2002

Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease.

Oral contraceptive use in women with factor V Leiden is associated with increased rates of venous thromboembolic events (VTEs). However, the effects of hormone replacement therapy (HRT) in postmenopausal women with factor V Leiden are not known. A nested case-control study was conducted among women with established coronary disease enrolled in 2 randomized clinical trials of HRT, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement and Atherosclerosis (ERA) trial. The Leiden mutation was present in 8 (16.7%) of 48 cases with VTE compared with only 7 (6.3%) of 112 controls (odds ratio [OR](Leiden) 3.3, 95% CI 1.1 to 9.8; P=0.03). In women without the factor V Leiden mutation, risk associated with HRT use was significantly increased (OR(HRT) 3.7, 95% CI 1.4 to 9.4; P<0.01). On the other hand, in women with the factor V Leiden mutation, the estimated risk associated with HRT was increased nearly 6-fold, although the CIs were wide and included unity (OR(HRT) 5.7, 95% CI 0.6 to 53.9; P=0.13). The OR for women with the Leiden mutation who were also assigned to HRT compared with wild-type women assigned to placebo was 14.1 (95% CI 2.7 to 72.4, P=0.0015). In women with the factor V Leiden mutation who were treated with HRT, the estimated absolute incidence of VTE was 15.4 of 1000 per year compared with 2.0 of 1000 per year in women without the mutation who were taking a placebo (P=0.0015). On the basis of these data, in women with coronary disease, the estimated number needed to screen for factor V Leiden to avoid an HRT-associated VTE during 5 years of treatment is 376. If factor V Leiden genotyping becomes less expensive, it could be cost effective to screen for the presence of the mutation before instituting HRT in women with coronary disease.

Aged↗

PubMed2002

Subgroup interactions in the Heart and Estrogen/Progestin Replacement Study: lessons learned.

BACKGROUND: The Heart and Estrogen/Progestin Replacement Study (HERS) showed no overall benefit of postmenopausal hormone treatment in women with coronary heart disease (CHD). We analyzed the HERS data to determine whether there were specific subgroups of women who responded differently to treatment, either during the first year or in the overall study. METHODS AND RESULTS: In the search for significant treatment interactions, we analyzed a total of 86 subgroups defined by baseline characteristics. These included demographics and lifestyle factors, laboratory and physical examination variables, medical history and symptoms by self-report, medication use, and prior CHD history by chart review. We examined within-subgroup treatment effects for baseline variables that significantly interacted with treatment assignment. Under the null hypothesis, 4 (5%) of the 86 interactions would be expected to be nominally significant (P<0.05) by chance alone at each time point. Six of the interaction values were P<0.05 at 1 year, and 3 were P<0.05 at trial completion. The findings are discussed in the context of known mechanisms of action and prior scientific knowledge. Use of digitalis and history of myocardial infarction emerged as 2 possible modifiers of the effect of hormone therapy during the first year, and lipoprotein(a) emerged as a possible modifier during the overall study. CONCLUSIONS: Extensive post hoc analyses did not identify any subgroup of HERS participants in which postmenopausal hormone treatment was clearly beneficial or harmful, but several possibilities emerged for testing in future trials.

Aged↗