William Whang

Dietary α-Linolenic Acid Intake and Risk of Sudden Cardiac Death and Coronary Heart Disease

Background— &agr;-Linolenic acid, an intermediate-chain n-3 fatty acid found primarily in plants, may decrease the risk of fatal coronary heart disease (CHD) through a reduction in fatal ventricular arrhythmias and sudden cardiac death (SCD). Methods and Results— We prospectively examined the association between dietary intake of &agr;-linolenic acid assessed via updated food-frequency questionnaires and the risk of SCD, other fatal CHD, and nonfatal myocardial infarction (MI) among 76 763 women participating in the Nurses’ Health Study who were free from cancer and completed a dietary questionnaire at baseline in 1984. During 18 years of follow-up, we identified 206 SCDs, 641 other CHD deaths, and 1604 nonfatal MIs. After controlling for coronary risk factors and other fatty acids, including long-chain n-3 fatty acids, the intake of &agr;-linolenic acid was inversely associated with the risk of SCD (P for trend, 0.02) but not with the risk of other fatal CHD or nonfatal MI. Compared with women in the lowest quintile of &agr;-linolenic acid intake, those in the highest 2 quintiles had a 38% to 40% lower SCD risk. This inverse relation with SCD risk was linear and remained significant even among women with high intakes of long-chain n-3 fatty acids. Conclusions— These prospective data suggest that increasing dietary intake of &agr;-linolenic acid may reduce the risk of SCD but not other types of fatal CHD or nonfatal MI in women. The specificity of the association between &agr;-linolenic acid and SCD supports the hypothesis that these n-3 fatty acids may have antiarrhythmic properties.

Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1- positive or BRCA2-positive patients

PURPOSE Young Ashkenazi Jewish women or those from high-risk families who test positive for BRCA1 or BRCA2 mutant genes have a significant risk of developing breast or ovarian cancer by the age of 70 years. Many question whether they should have prophylactic surgical procedures, ie, bilateral mastectomy and/or oophorectomy. METHODS A Markov model was developed to determine the survival, quality of life, and cost-effectiveness of prophylactic surgical procedures. The probabilities of developing breast and ovarian cancer were based on literature review among women with the BRCA1 or BRCA2 gene and mortality rates were determined from Surveillance, Epidemiology, and End Results (SEER) data for 1973 to 1992. The costs for hospital and ambulatory care were estimated from Health Care Financing Administration (HCFA) payments in 1995, supplemented by managed care and fee-for-service data. Utility measures for quality-adjusted life-years (QALYs) were explicitly determined using the time-trade off method. Estimated risks for breast and ovarian cancer after prophylactic surgeries were obtained from the literature. RESULTS For a 30-year-old woman, according to her cancer risks, prophylactic oophorectomy improved survival by 0.4 to 2.6 years; mastectomy, by 2.8 to 3.4 years; and mastectomy and oophorectomy, by 3.3 to 6.0 years over surveillance. The QALYs saved were 0.5 for oophorectomy and 1.9 for the combined procedures in the high-risk model. Prophylactic surgeries were cost-effective compared with surveillance for years of life saved, but not for QALYs. CONCLUSION Among women who test positive for a BRCA1 or BRCA2 gene mutation, prophylactic surgery at a young age substantially improves survival, but unless genetic risk of cancer is high, provides no benefit for quality of life. Prophylactic surgery is cost-effective for years of life saved compared with other medical interventions that are deemed cost-effective.

Don't worry, be happy: positive affect and reduced 10-year incident coronary heart disease: the Canadian Nova Scotia Health Survey.

AIMS Positive affect is believed to predict cardiovascular health independent of negative affect. We examined whether higher levels of positive affect are associated with a lower risk of coronary heart disease (CHD) in a large prospective study with 10 years of follow-up. METHODS AND RESULTS We examined the association between positive affect and cardiovascular events in 1739 adults (862 men and 877 women) in the 1995 Nova Scotia Health Survey. Trained nurses conducted Type A Structured Interviews, and coders rated the degree of outwardly displayed positive affect on a five-point scale. To test that positive affect predicts incident CHD when controlling for depressive symptoms and other negative affects, we used as covariates: Center for Epidemiological Studies Depressive symptoms Scale, the Cook Medley Hostility scale, and the Spielberger Trait Anxiety Inventory. There were 145 (8.3%) acute non-fatal or fatal ischaemic heart disease events during the 14 916 person-years of observation. In a proportional hazards model controlling for age, sex, and cardiovascular risk factors, positive affect predicted CHD (adjusted HR, 0.78; 95% CI 0.63-0.96 per point; P = 0.02), the covariate depressive symptoms continued to predict CHD as had been published previously in the same patients (HR, 1.04; 95% CI 1.01-1.07 per point; P = 0.004) and hostility and anxiety did not (both P > 0.05). CONCLUSION In this large, population-based study, increased positive affect was protective against 10-year incident CHD, suggesting that preventive strategies may be enhanced not only by reducing depressive symptoms but also by increasing positive affect.

Mechanisms of Death in the CABG Patch Trial A Randomized Trial of Implantable Cardiac Defibrillator Prophylaxis in Patients at High Risk of Death After Coronary Artery Bypass Graft Surgery

BACKGROUND The CABG Patch trial compared prophylactic implantable cardiac-defibrillator (ICD) implantation with no antiarrhythmic therapy in coronary bypass surgery patients who had a left ventricular ejection fraction <0.36 and an abnormal signal-averaged ECG. There were 102 deaths among the 446 ICD group patients and 96 deaths among the 454 control group patients, a hazard ratio of 1.07 (P=0.63). The mechanisms of death were classified, and hypotheses were tested about the effects of ICD therapy on arrhythmic and nonarrhythmic cardiac deaths in the CABG Patch Trial and the Multicenter Automatic Defibrillator Implantation Trial (MADIT). METHODS AND RESULTS The 198 deaths in the trial were reviewed by an independent Events Committee and classified by the method of Hinkle and Thaler. Only 54 deaths (27%) occurred out of hospital; 145 deaths (73%) were witnessed. Seventy-nine (82%) of the 96 deaths in the control group and 76 (75%) of the 102 deaths in the ICD group were due to cardiac causes. Cumulative arrhythmic mortality at 42 months was 6.9% in the control group and 4.0% in the ICD group (P=0. 057). Cumulative nonarrhythmic cardiac mortality at 42 months was 12. 4% in the control group and 13.0% in the ICD group (P=0.275). Death due to pump failure was significantly associated with death >1 hour from the onset of symptoms, dyspnea within 7 days of death, and overt heart failure within 7 days of death. CONCLUSIONS In the CABG Patch Trial, ICD therapy reduced arrhythmic death 45% without significant effect on nonarrhythmic deaths. Because 71% of the deaths were nonarrhythmic, total mortality was not significantly reduced.

Heart Failure and the Risk of Shocks in Patients With Implantable Cardioverter Defibrillators Results From the Triggers Of Ventricular Arrhythmias (TOVA) Study

Background—Left ventricular ejection fraction (LVEF) predicts device discharges in patients with implantable cardioverter-defibrillators (ICDs). The relationship between severity of congestive heart failure (CHF) and ICD discharges is less clear. Methods and Results—We prospectively analyzed the association between CHF and risk of appropriate ICD discharges in the Triggers Of Ventricular Arrhythmias (TOVA) study, a cohort study of ICD patients conducted at 31 centers in the United States. Reported shocks were confirmed for sustained ventricular tachycardia (VT) or fibrillation (VF) by analysis of stored electrograms. Proportional hazards models included CHF categorized by New York Heart Association class. Baseline CHF was present among 502 (44%) of 1140 patients; 170 (34%) had class I, 230 (46%) had class II, 97 (19%) had class III, and only 5 (1%) had class IV symptoms. During median follow-up of 212 days, 92 patients experienced 1 or more appropriate ICD discharges. Class III CHF was associated in a statistically significantly manner with ICD discharge for VT/VF (hazard ratio 2.40, 95% CI 1.16 to 4.98), even with adjustment for LVEF. The combination of LVEF <0.20 and class III symptoms resulted in a particularly high risk of shocks for VT/VF (hazard ratio 3.90, 95% CI 1.28 to 11.92). Conclusions—Class III CHF, an easily accessible clinical measure, is an independent risk factor, along with LVEF, for ventricular arrhythmias that require shock therapy among ICD patients. Whether patients with class III CHF benefit to a greater degree from ICDs and whether aggressive treatment of CHF in ICD patients may prevent ventricular arrhythmias remains to be determined.

Bayesian estimation of cost-effectiveness ratios from clinical trials

Estimation of the incremental cost-effectiveness ratio (ICER) is difficult for several reasons: treatments that decrease both cost and effectiveness and treatments that increase both cost and effectiveness can yield identical values of the ICER; the ICER is a discontinuous function of the mean difference in effectiveness; and the standard estimate of the ICER is a ratio. To address these difficulties, we have developed a Bayesian methodology that involves computing posterior probabilities for the four quadrants and separate interval estimates of ICER for the quadrants of interest. We compute these quantities by simulating draws from the posterior distribution of the cost and effectiveness parameters and tabulating the appropriate posterior probabilities and quantiles. We demonstrate the method by re-analysing three previously published clinical trials.

Diabetes and outcomes of coronary artery bypass graft surgery in patients with severe left ventricular dysfunction: results from The CABG Patch Trial database

OBJECTIVES We examined the relationship between diabetes mellitus and outcomes after coronary artery bypass graft (CABG) surgery in patients with severe left ventricular (LV) dysfunction. BACKGROUND Although diabetes is associated with poor outcomes after CABG surgery among unselected patients, the relationship between diabetes and mortality after CABG surgery among patients with LV dysfunction is less certain. METHODS Using data from The CABG Patch Trial, a study of implantable cardiac defibrillator therapy, we analyzed 900 patients with ejection fraction <0.36 who underwent CABG surgery from 1990 to 1996. RESULTS Diabetics comprised 38% of the patients, and 48% of diabetics were prescribed insulin. Diabetes was associated with hypertension, peripheral vascular disease, history of stroke, clinical heart failure and rales on physical exam. Diabetics were at higher risk for postoperative superficial sternal wound infection and renal failure. With an average follow-up time of 32 +/-16 months, actuarial all-cause mortality 48 months after CABG surgery was 26% in diabetics and 24% in nondiabetics (p = 0.66, log-rank test). Diabetes was not associated with long-term mortality in Cox multiple regression analyses. Actuarial re-hospitalization rates 48 months after CABG surgery were 85% in diabetics and 69% in nondiabetics (p = 0.0001, log-rank test). Diabetics had a 44% higher risk of re-hospitalization for any cause (p = 0.0001) and a 24% higher risk of re-admission for cardiac causes (p < 0.05). Unexpectedly, fewer arrhythmic events were found in diabetics. CONCLUSIONS Diabetes was not a predictor of mortality after CABG surgery among patients with LV dysfunction despite associated comorbidities. However, diabetes was associated with increased postoperative complications and re-hospitalization.

Centralized, Stepped, Patient Preference-Based Treatment for Patients With Post-Acute Coronary Syndrome Depression CODIACS Vanguard Randomized Controlled Trial

IMPORTANCE Controversy remains about whether depression can be successfully managed after acute coronary syndrome (ACS) and the costs and benefits of doing so. OBJECTIVE To determine the effects of providing post-ACS depression care on depressive symptoms and health care costs. DESIGN Multicenter randomized controlled trial. SETTING Patients were recruited from 2 private and 5 academic ambulatory centers across the United States. PARTICIPANTS A total of 150 patients with elevated depressive symptoms (Beck Depression Inventory [BDI] score ≥10) 2 to 6 months after an ACS, recruited between March 18, 2010, and January 9, 2012. INTERVENTIONS Patients were randomized to 6 months of centralized depression care (patient preference for problem-solving treatment given via telephone or the Internet, pharmacotherapy, both, or neither), stepped every 6 to 8 weeks (active treatment group; n = 73), or to locally determined depression care after physician notification about the patients depressive symptoms (usual care group; n = 77). MAIN OUTCOME MEASURES Change in depressive symptoms during 6 months and total health care costs. RESULTS Depressive symptoms decreased significantly more in the active treatment group than in the usual care group (differential change between groups, -3.5 BDI points; 95% CI, -6.1 to -0.7; P = .01). Although mental health care estimated costs were higher for active treatment than for usual care, overall health care estimated costs were not significantly different (difference adjusting for confounding, -

Benefits and Costs of Screening Ashkenazi Jewish Women for BRCA1 and BRCA2

325; 95% CI, -

Relations Between QRS|T Angle, Cardiac Risk Factors, and Mortality in the Third National Health and Nutrition Examination Survey (NHANES III)

2639 to