Sonja M. McKinlay

Early revascularization in acute myocardial infarction complicated by cardiogenic shock

BACKGROUND The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. METHODS Patients with shock due to left ventricular failure complicating myocardial infarction were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty. Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups. The primary end point was mortality from all causes at 30 days. Six-month survival was a secondary end point. RESULTS The mean age of the patients was 66+/-10 years, 32 percent were women and 55 percent were transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87 percent underwent revascularization; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups (46.7 percent and 56.0 percent, respectively; difference, -9.3 percent; 95 percent confidence interval for the difference, -20.5 to 1.9 percent; P=0.11). Six-month mortality was lower in the revascularization group than in the medical-therapy group (50.3 percent vs. 63.1 percent, P=0.027). CONCLUSIONS In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days. However, after six months there was a significant survival benefit. Early revascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenic shock.

Spironolactone for Heart Failure with Preserved Ejection Fraction

BACKGROUND Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. CONCLUSIONS In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

Outcomes of a field trial to improve children's dietary patterns and physical activity. The Child and Adolescent Trial for Cardiovascular Health. CATCH collaborative group.

OBJECTIVE To assess the outcomes of health behavior interventions, focusing on the elementary school environment, classroom curricula, and home programs, for the primary prevention of cardiovascular disease. DESIGN A randomized, controlled field trial at four sites with 56 intervention and 40 control elementary schools. Outcomes were assessed using prerandomization measures (fall 1991) and follow-up measures (spring 1994). PARTICIPANTS A total of 5106 initially third-grade students from ethnically diverse backgrounds in public schools located in California, Louisiana, Minnesota, and Texas. INTERVENTION Twenty-eight schools participated in a third-grade through fifth-grade intervention including school food service modifications, enhanced physical education (PE), and classroom health curricula. Twenty-eight additional schools received these components plus family education. MAIN OUTCOME MEASURES At the school level, two primary end points were changes in the fat content of food service lunch offerings and the amount of moderate-to-vigorous physical activity in the PE programs. At the level of the individual student, serum cholesterol change was the primary end point and was used for power calculations for the study. Individual level secondary end points included psychological factors, recall measures of eating and physical activity patterns, and other physiologic measures. RESULTS In intervention school lunches, the percentage of energy intake from fat fell significantly more (from 38.7% to 31.9%) than in control lunches (from 38.9% to 36.2%)(P<.001). The intensity of physical activity in PE classes during the Child and Adolescent Trial for Cardiovascular Health (CATCH) intervention increased significantly in the intervention schools compared with the control schools (P<.02). Self-reported daily energy intake from fat among students in the intervention schools was significantly reduced (from 32.7% to 30.3%) compared with that among students in the control schools (from 32.6% to 32.2%)(P<.001). Intervention students reported significantly more daily vigorous activity than controls (58.6 minutes vs 46.5 minutes; P<.003). Blood pressure, body size, and cholesterol measures did not differ significantly between treatment groups. No evidence of deleterious effects of this intervention on growth or development was observed. CONCLUSION The CATCH intervention was able to modify the fat content of school lunches, increase moderate-to-vigorous physical activity in PE, and improve eating and physical activity behaviors in children during 3 school years.

A longitudinal analysis of the association between menopause and depression Results from the Massachusetts women's health study

The present article prospectively examines the effect of change in menopause status on depression, while controlling for prior depression. This is a longitudinal follow-up of previous cross-sectional analyses reported by McKinlay, McKinlay, and Brambilla who examined the relative contribution of menopause to depression. The data derive from the Massachusetts Womens Health Study, a 5-year longitudinal study of a cohort of 2565 women aged 45 to 55 years at baseline (1981 to 1982). Results show that prior depression is the variable most predictive of subsequent depression, as measured by the Center for Epidemiologic Studies-Depression (CES-D) scale. Onset of natural menopause was not associated with increased risk of depression. Experiencing a long perimenopausal period (at least 27 months), however, was associated with increased risk of depression. The association between a long perimenopause and depression appeared to be explained by increased menopausal symptoms rather than by the menopause status itself. The observed increase in depression during a lengthy perimenopause appears to be transitory.

Smoking and age at menopause in women.

Although women can expect to live one half of their adult lives beyond menopause, knowledge about this physiologic event and its various influences on subsequent health and quality of life remains incomplete. In Massachusetts we studied a population-based random sample of 7828 white women, aged 45 to 55 years (response rate, 77%). The median age at last menstruation for the sample is 51.4 +/- 0.19 (SE) years years, and we found no evidence of a secular trend towards a later age at menopause in the last 25 years. Current smokers reach menopause an average of 1.74 years earlier than nonsmokers (t = 3.78, p less than 0.01), but the quantity smoked has a negligible effect. Other potential correlates measured--education and marital status, number of children, and urban/rural residence--have little effect on the age at menopause. The results confirm earlier, more tentative findings from clinical populations.

The relative contributions of endocrine changes and social circumstances to depression in mid-aged women

Although researched extensively over several decades, the prevalence, costs and reasons for depression among women during the middle years remain a challenge to public health. A vast literature is distilled into two predominant schools of thought, each with profoundly different implications for research and clinical practice. One school (the estrogen-deficiency perspective) holds that depression is associated with or triggered by endocrine changes in women around 50 years of age (menopause). A second school (the social-circumstances perspective) holds that depression is related to social circumstances encountered frequently by women during their fourth and fifth decades. Employing data from a randomly selected cohort of 2,500 premenopausal women sampled in Massachusetts, this paper shows that: * depression is associated with a surgical menopause and may even be a cause rather than a consequence of this surgery for this atypical group of women; * depression is not associated with the natural changes from preto immediately postmenopause; and * the most marked increases in depression are associated with multiple causes of worry and multiple roles among currently married women (including paid work, adolescent children, ailing husbands, and aging parents or parents-in-law). Some implications of these findings are discussed in the context of a rapidly aging population.

Regional Variation in Patients and Outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) Trial

Background— Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas). Methods and Results— To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P<0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone. Conclusions— This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

A prospective study of factors affecting age at menopause.

Abstract This paper describes a multivariate analysis of a 3-year prospective study of the covariates of age at menopause among women who were randomly sampled from a general population. This approach avoids three problems that may account for the inconsistent results of prior studies: recall bias in retrospectively collected data, failure to control confounding in data analyses, and self-selection in the target populations. At baseline, the 2014 subjects in this study were 46.5–56.5 years old and still menstruating. Median age at last menstruation, estimated from a model of the marginal distribution of age at menopause, was 50.7 years. When covariates were considered singly, age at menopause varied with smoking, education and income but not with marital status, parity, location, height, weight or use of either oral contraceptives or menopausal estrogens. Multivariate analyses showed that education and income were confounded with smoking status. The results indicate that many previously identified sources of variation in age at menopause reflect confounding with smoking and self-selection in target populations, rather than real effects.

The normal menopause transition: an overview

OBJECTIVES This review emphasizes results from population based studies in order to provide a reliable knowledge base and define major knowledge gaps for future research. METHODS The review systematically addresses the following aspects of menopause research: definition of menopause and menopause transitions; age at natural menopause and at inception of perimenopause; factors affecting timing and length of menopause transitions; concurrent hormone, menstrual and vascular changes. Under each substantive heading, available reports of original research are reviewed, assessed for reliability and summarized with respect to their contribution to the knowledge base. RESULTS From this review, the following reliable information can be summarized: median age at natural menopause in Caucasian women occurs between 50 and 51-55 years of age, is not affected by timing of surgical menopause and is affected by cigarette smoking, with current smokers having an earlier menopause by 1.5-2.0 years. No other factors appear to have an independent effect on age at menopause. There is no evidence of any secular trend in age at menopause. Evidence is accumulating that most physiological change associated with menopause either occurs or begins before the final menstrual period. CONCLUSIONS We lack reliable information on the following: estimates of age at menopause from non-industrialized countries and diverse ethnic groups; information on perimenopause; differing perceptions of menopause, cross culturally; multi-disciplinary prospective data that can link various processes into coherent patterns.

Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction: Baseline Findings From the Echocardiographic Study of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial

Background— Heart failure with preserved ejection fraction (HFpEF) is associated with substantial morbidity and mortality. Existing data on cardiac structure and function in HFpEF suggest significant heterogeneity in this population. Methods and Results— Echocardiograms were obtained from 935 patients with HFpEF (left ventricular ejection fraction ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial before initiation of randomized therapy. Average age was 70±10 years, 49% were women, 14% were of African descent, and comorbidities were highly prevalent. Centralized quantitative analysis in a blinded core laboratory demonstrated a mean left ventricular ejection fraction of 59.3±7.9%, with prevalent concentric left ventricular remodeling (34%) and hypertrophy (43%), and left atrial enlargement (53%). Diastolic dysfunction was present in 66% of gradable participants and was significantly associated with greater left ventricular hypertrophy and a higher prevalence of left atrial enlargement. Doppler evidence of pulmonary hypertension was present in 36%. At least 1 measure of structural heart disease was present in 93% of patients. Conclusions— Patients enrolled in TOPCAT demonstrated heterogeneous patterns of ventricular remodeling, with high prevalence of structural heart disease, including left ventricular hypertrophy and left atrial enlargement, in addition to pulmonary hypertension, each of which has been associated with adverse outcomes in HFpEF. Diastolic function was normal in approximately one third of gradable participants, highlighting the heterogeneity of the cardiac phenotype in this syndrome. These findings deepen our understanding of the TOPCAT trial population and expand our knowledge of the diversity of the cardiac phenotype in HFpEF. Clinical Trial Registration—URL: . Unique identifier: [NCT00094302][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00094302&atom=%2Fcirchf%2F7%2F1%2F104.atomBackground— Heart failure with preserved ejection fraction (HFpEF) is associated with substantial morbidity and mortality. Existing data on cardiac structure and function in HFpEF suggest significant heterogeneity in this population. Methods and Results— Echocardiograms were obtained from 935 patients with HFpEF (left ventricular ejection fraction ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial before initiation of randomized therapy. Average age was 70±10 years, 49% were women, 14% were of African descent, and comorbidities were highly prevalent. Centralized quantitative analysis in a blinded core laboratory demonstrated a mean left ventricular ejection fraction of 59.3±7.9%, with prevalent concentric left ventricular remodeling (34%) and hypertrophy (43%), and left atrial enlargement (53%). Diastolic dysfunction was present in 66% of gradable participants and was significantly associated with greater left ventricular hypertrophy and a higher prevalence of left atrial enlargement. Doppler evidence of pulmonary hypertension was present in 36%. At least 1 measure of structural heart disease was present in 93% of patients. Conclusions— Patients enrolled in TOPCAT demonstrated heterogeneous patterns of ventricular remodeling, with high prevalence of structural heart disease, including left ventricular hypertrophy and left atrial enlargement, in addition to pulmonary hypertension, each of which has been associated with adverse outcomes in HFpEF. Diastolic function was normal in approximately one third of gradable participants, highlighting the heterogeneity of the cardiac phenotype in this syndrome. These findings deepen our understanding of the TOPCAT trial population and expand our knowledge of the diversity of the cardiac phenotype in HFpEF. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.