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Biomedical subjects

Rita F Redberg

Publications and source records attributed to Rita F Redberg.

At least 19 recordsLinked to original sources

Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors: results from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) initiative.

BACKGROUND: Glycoprotein (GP) IIb/IIIa inhibitors are beneficial in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); their safe use in women, however, remains a concern. The contribution of dosing to the observed sex-related differences in bleeding is unknown. METHODS AND RESULTS: We explored the relationship between patient sex, GP IIb/IIIa inhibitor use, dose, and bleeding in 32 601 patients with NSTE ACS across 400 CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) hospitals, of whom 18 436 were treated. GP IIb/IIIa inhibitor dose was defined as excessive if not reduced when creatinine clearance was < 50 mL/min for eptifibatide or < 30 mL/min for tirofiban. Major bleeding was defined as a hematocrit drop > or = 0.12, need for transfusion, or intracranial bleeding. Major bleeding was adjusted for clinical factors and antithrombotic dose. The risk for bleeding attributable to excess GP IIb/IIIa dose was determined by sex using prevalence and adjusted odds ratios (ORs). Women had higher rates of major bleeding than men among those treated with GP IIb/IIIa inhibitors (15.7% versus 7.3%, P<0.0001) and among those not treated (8.5% versus 5.4%, P<0.0001). Despite similar serum creatinine levels, creatinine clearance averaged 20 points lower among treated women than men. Treated women were also more likely to receive excess GP IIb/IIIa doses than men (46.4% versus 17.2%, P<0.0001; adjusted OR 3.81, 95% confidence interval [CI] 3.39 to 4.27). Excess dosing was associated with increased risk of bleeding in women (OR 1.72, 95% CI 1.30 to 2.28) and men (OR 1.27, 95% CI 0.97 to 1.66); however, bleeding risk attributable to dosing was much higher in women (25.0% versus 4.4%). CONCLUSIONS: Women experience more bleeding than men whether or not they are treated with GP IIb/IIIa inhibitors; however, because of frequent excessive dosing in women, up to one fourth of this sex-related risk difference in bleeding is avoidable. Appropriate dosing will improve care of all patients with NSTE ACS, with a particular benefit for women.

Acute Disease↗

Screening asymptomatic diabetic patients for coronary artery disease: why not?

Given the elevated risk of cardiovascular events and the higher prevalence of silent coronary artery disease (CAD) in diabetic versus non-diabetic patients, screening asymptomatic diabetic patients for CAD is an appealing concept. However, many factors argue against implementing a broad-based screening program at the present time. Foremost is the lack of any published data demonstrating that a prospectively applied screening program improves outcome in asymptomatic diabetic patients. The true prevalence of CAD, and in particular prognostically important CAD, in this population is uncertain. Consensus documents recommend more aggressive treatment of hypertension and hyperlipidemia solely on the basis of diabetes status, without differentiation based on the presence or absence of identifiable CAD. There is no evidence that use of anti-ischemic medication can alter the natural history of CAD in these patients. Retrospectively performed studies using stress single-photon emission computed tomography (SPECT) imaging have reported that approximately 50% and 20% of patients have abnormal and high-risk images, respectively. However, the only prospectively designed study, the DIAD (Detection of Ischemia in Asymptomatic Diabetics) study, reported a much lower percentage of abnormal SPECT images (16%) and images with a very large (>/=10% of the left ventricle) defect (1%). The financial implications of screening all asymptomatic diabetic patients determined to be at intermediate and high risk by clinical scoring systems is enormous. Clearly more data are needed to address this issue. Future studies should consider possible methods to enrich the patient subset that might benefit from screening and should include carefully performed cost-effective analyses.

Coronary Artery Disease↗

Enhanced risk assessment in asymptomatic individuals with exercise testing and Framingham risk scores.

BACKGROUND: National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines recommend the use of Framingham risk scores (FRS) for cardiovascular assessment of asymptomatic individuals. We hypothesized that risk prediction could be improved with 2 non-ECG exercise test measures, exercise capacity (metabolic equivalents, or METs) and heart rate recovery (HRR). METHODS AND RESULTS: An asymptomatic cohort with baseline treadmill tests (n=6126; 46% women, FRS <20%) was followed up prospectively for 20 years. Individuals with low (median or less) HRR or METs experienced 91% of all cardiovascular disease (CVD) deaths (225/246). After FRS adjustment, low HRR and METs individually were highly significant predictors of CVD death, but low HRR and METs together were associated with substantially higher risk (adjusted hazard ratio compared with high HRR/high METs for women 8.51, 95% CI 3.65 to 19.84; for men, 3.53, 95% CI 2.03 to 6.15; P<0.001 for both). At 10-year follow-up, FRS-adjusted CVD death risk associated with low HRR/low METs was less than at 20 years but remained significant (women 3.83, 95% CI 1.09 to 13.47, and men 2.70, 95% CI 1.11 to 6.55). The application of HRR/METs information to FRS assessment identified those at high risk (>0.5% annual CVD mortality) in half of women with FRS 6% to 9% and 10% to 19% and just under half of men with FRS 10% to 19%. Low HRR/low METs was also associated with an increased relative risk of CVD death in individuals with low-risk FRS (FRS <6% in women and <10% in men), but absolute CVD mortality rates were low in this subgroup. CONCLUSIONS: Exercise testing may be a useful adjunct for clinical risk assessment in asymptomatic women with FRS 6% to 19% and men with FRS 10% to 19%.

Adult↗

Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: Consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association.

Cardiovascular disease is the leading cause of mortality for women in the United States. Coronary heart disease, which includes coronary atherosclerotic disease, myocardial infarction, acute coronary syndromes, and angina, is the largest subset of this mortality, with >240,000 women dying annually from the disease. Atherosclerotic coronary artery disease (CAD) is the focus of this consensus statement. Research continues to report underrecognition and underdiagnosis of CAD as contributory to high mortality rates in women. Timely and accurate diagnosis can significantly reduce CAD mortality for women; indeed, once the diagnosis is made, it does appear that current treatments are equally effective at reducing risk in both women and men. As such, noninvasive diagnostic and prognostic testing offers the potential to identify women at increased CAD risk as the basis for instituting preventive and therapeutic interventions. Nevertheless, the recent evidence-based practice program report from the Agency for Healthcare Research and Quality noted the paucity of women enrolled in diagnostic research studies. Consequently, much of the evidence supporting contemporary recommendations for noninvasive diagnostic studies in women is extrapolated from studies conducted predominantly in cohorts of middle-aged men. The majority of diagnostic and prognostic evidence in cardiac imaging in women and men has been derived from observational registries and referral populations that are affected by selection and other biases. Thus, a better understanding of the potential impact of sex differences on noninvasive cardiac testing in women may greatly improve clinical decision making. This consensus statement provides a synopsis of available evidence on the role of the exercise ECG and cardiac imaging modalities, both those in common use as well as developing technologies that may add clinical value to the diagnosis and risk assessment of the symptomatic and asymptomatic woman with suspected CAD.

Coronary Artery Disease↗

Acute coronary syndromes in women: is treatment different? Should it be?

The vast majority of acute coronary syndrome (ACS) trials conducted over the past two decades support the view that women have persistently higher mortality and morbidity despite the introduction of new medical therapies and devices. Even after adjustment for older age, higher prevalence of diabetes, hypertension, heart failure, smaller vessel size, and late presentation, some studies still point to a persistent sex disadvantage. Even in contemporary practice, women continue to have longer delays in presentation and treatment. Selection bias in unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) trials allows inclusion of large numbers of women with clinically insignificant coronary disease and may mistakenly shift results toward apparent benefit of a less aggressive approach. This bias causes further difficulty in determining efficacy and safety of new antithrombotic agents such as direct thrombin inhibitors and glycoprotein IIb/IIa inhibitors across the spectrum of ACS. In trials of UA/NSTEMI, use of objective evidence of ischemia such as elevated troponin levels, would greatly assist the determination of efficacy and benefit in women. Enrollment of more women in clinical trials and timely sex-specific analysis would promote a better understanding of the role of female gender in ACS and would facilitate better care of all patients.

Angina, Unstable↗

Ability of exercise testing to predict cardiovascular and all-cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study.

CONTEXT: The value of exercise testing in women has been questioned. OBJECTIVE: To determine the prognostic value of exercise testing in a population-based cohort of asymptomatic women followed up for 20 years. DESIGN AND SETTING: Near-maximal Bruce-protocol treadmill test data from the Lipid Research Clinics Prevalence Study (1972-1976) with follow-up through 1995. PARTICIPANTS: A total of 2994 asymptomatic North American women, aged 30 to 80 years, without known cardiovascular disease. MAIN OUTCOME MEASURES: Cardiovascular and all-cause mortality. RESULTS: There were 427 (14%) deaths during 20 years of follow-up, of which 147 were due to cardiovascular causes. Low exercise capacity, low heart rate recovery (HRR), and not achieving target heart rate were independently associated with increased all-cause and cardiovascular mortality. There was no increased cardiovascular death risk for exercise-induced ST-segment depression (age-adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.57-1.80; P =.96). The age-adjusted hazard ratio for cardiovascular death for every metabolic equivalent (MET) decrement in exercise capacity was 1.20 (95% CI, 1.18-1.30; P<.001); for every 10 beats per minute decrement in HRR, the hazard ratio was 1.36 (95% CI, 1.19-1.55; P<.001). After adjusting for multiple other risk factors, women who were below the median for both exercise capacity and HRR had a 3.5-fold increased risk of cardiovascular death (95% CI, 1.57-7.86; P =.002) compared with those above the median for both variables. Among women with low risk Framingham scores, those with below median levels of both exercise capacity and HRR had significantly increased risk compared with women who had above median levels of these 2 exercise variables, 44.5 and 3.5 cardiovascular deaths per 10 000 person-years, respectively (hazard ratio for cardiovascular death, 12.93; 95% CI, 5.62-29.73; P<.001). CONCLUSION: The prognostic value of exercise testing in asymptomatic women derives not from electrocardiographic ischemia but from fitness-related variables.

Adult↗