Candace K. McClure

Adverse Cardiovascular Outcomes in Women With Nonobstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project

BACKGROUND Women with clinical findings suggestive of ischemia but without findings of obstructive coronary artery disease (CAD) on angiography represent a frequent clinical problem; predicting prognosis is challenging. METHODS The Womens Ischemia Syndrome Evaluation (WISE) study examined symptomatic women referred for clinically indicated coronary angiography and followed up for a mean 5.2 years. The St James Women Take Heart (WTH) Project enrolled asymptomatic, community-based women with no history of heart disease who were followed up for 10 years. We compared cardiovascular events (ie, myocardial infarction, stroke, and hospitalization for heart failure) and death in 540 WISE women with suspected ischemia but no angiographic evidence of obstructive CAD with those from a cohort of 1000 age- and race-matched WTH women. RESULTS Compared with the WISE women, asymptomatic WTH women had a lower prevalence of obesity, family history of CAD, hypertension, and diabetes mellitus (P < .001). Five-year annualized event rates for cardiovascular events were 16.0% in WISE women with nonobstructive CAD (stenosis in any coronary artery of 1%-49%), 7.9% in WISE women with normal coronary arteries (stenosis of 0% in all coronary arteries), and 2.4% in asymptomatic WTH women (P < or = .002), after adjusting for baseline CAD risk factors. The cardiovascular events were most frequent in women with 4 or more cardiac risk factors, with the 5-year annualized cardiovascular event rate being 25.3% in women with nonobstructive CAD, 13.9% in WISE women with normal coronary arteries, and 6.5% in asymptomatic women (P = .003). CONCLUSION Women with symptoms and signs suggestive of ischemia but without obstructive CAD are at elevated risk for cardiovascular events compared with asymptomatic community-based women.

Depression, the metabolic syndrome and cardiovascular risk.

Background: The relationship between depression and the metabolic syndrome is unclear, and whether metabolic syndrome explains the association between depression and cardiovascular disease (CVD) risk is unknown. Methods: We studied 652 women who received coronary angiography as part of the Womens Ischemia Syndrome Evaluation (WISE) study and completed the Beck Depression Inventory (BDI). Women who had both elevated depressive symptoms (BDI ≥10) and a previous diagnosis of depression were considered at highest risk, whereas those with one of the two conditions represented an intermediate group. The metabolic syndrome was defined according to the ATP-III criteria. The main outcome was incidence of adverse CVD events (hospitalizations for myocardial infarction, stroke, congestive heart failure, and CVD-related mortality) over a median follow-up of 5.9 years. Results: After adjusting for demographic factors, lifestyle and functional status, both depression categories were associated with about 60% increased odds for metabolic syndrome compared with no depression (p = .03). The number of metabolic syndrome risk factors increased gradually across the three depression categories (p = .003). During follow-up, 104 women (15.9%) experienced CVD events. In multivariable analysis, women with both elevated symptoms and a previous diagnosis of depression had 2.6 times higher risk of CVD. When metabolic syndrome was added to the model, the risk associated with depression only decreased by 7%, and both depression and metabolic syndrome remained significant predictors of CVD. Conclusions: In women with suspected coronary artery disease, the metabolic syndrome is independently associated with depression but explains only a small portion of the association between depression and incident CVD. BDI = Beck Depression Inventory; CAD = coronary artery disease; CVD = cardiovascular disease; DASI = Duke Activity Status Inventory; HDL = high-density lipoprotein; LDL = low-density lipoprotein; WISE = Womens Ischemia Syndrome Evaluation; NHLBI = National Heart, Lung, and Blood Institute.

Lactation and Maternal Risk of Type 2 Diabetes: A Population-based Study

BACKGROUND Lactation has been associated with improvements in maternal glucose metabolism. METHODS We explored the relationships between lactation and risk of type 2 diabetes in a well-characterized, population-representative cohort of women, aged 40-78 years, who were members of a large integrated health care delivery organization in California and enrolled in the Reproductive Risk factors for Incontinence Study at Kaiser (RRISK), between 2003 and 2008. Multivariable logistic regression was used to control for age, parity, race, education, hysterectomy, physical activity, tobacco and alcohol use, family history of diabetes, and body mass index while examining the impact of duration, exclusivity, and consistency of lactation on risk of having developed type 2 diabetes. RESULTS Of 2233 women studied, 1828 were mothers; 56% had breastfed an infant for > or =1 month. In fully adjusted models, the risk of type 2 diabetes among women who consistently breastfed all of their children for > or =1 month remained similar to that of women who had never given birth (odds ratio [OR] 1.01; 95% confidence interval [CI], 0.56-1.81). In contrast, mothers who had never breastfed an infant were more likely to have developed type 2 diabetes than nulliparous women (OR 1.93; 95% CI, 1.14-3.27) [corrected]. Mothers who never exclusively breastfed were more likely to have developed type 2 diabetes than mothers who exclusively breastfed for 1-3 months (OR 1.52; 95% CI, 1.11-2.10). CONCLUSIONS Risk of type 2 diabetes increases when term pregnancy is followed by <1 month of lactation, independent of physical activity and body mass index in later life. Mothers should be encouraged to exclusively breastfeed all of their infants for at least 1 month.

Social networks and incident stroke among women with suspected myocardial ischemia

Objective: To describe the prospective relationship between social networks and nonfatal stroke events in a sample of women with suspected myocardial ischemia. Social networks are an independent predictor of all-cause and cardiovascular mortality, but their relationship with stroke events in at-risk populations is largely unknown. Method: A total of 629 women (mean age = 59.6 ± 11.6 years) were evaluated at baseline for cardiovascular disease risk factors as part of a protocol including coronary angiography; the subjects were followed over a median 5.9 years to track the incidence of cardiovascular events including stroke. Participants also completed the Social Network Index (SNI), measuring the presence/absence of 12 types of common social relationships. Results: Stroke events occurred among 5.1% of the sample over follow-up. More isolated women were older and less educated, with higher rates of smoking and hypertension, and increased use of cardiovascular medications. Women with smaller social networks were also more likely to show elevations (scores of ≥10) on the Beck Depression Inventory (54% versus 41%, respectively; p = .003). Relative to women with higher SNI scores, Cox regression results indicated that more isolated women experienced strokes at greater than twice the rate of those with more social relationships after adjusting for covariates (hazard ratio = 2.7; 95% Confidence Interval = 1.1–6.7). Conclusions: Smaller social networks are a robust predictor of stroke in at-risk women, and the magnitude of the association rivals that of conventional risk factors. CAD = coronary artery disease; SES = socioeconomic status; CVD = cardiovascular disease; WISE = Womens Ischemia Syndrome Evaluation; PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft; SNI = Social Network Index; BDI = Beck Depression Inventory; HR = hazard ratio.

Lactation and Maternal Measures of Subclinical Cardiovascular Disease

OBJECTIVE: To examine the relationship between lactation and subclinical cardiovascular disease in a population free of clinical cardiovascular disease. METHODS: We conducted a cross-sectional analysis of 297 women who reported at least one live birth on enrollment in the Study of Women Across the Nation–Heart Study. Participants were mothers aged 45–58 years who were free of clinical cardiovascular disease. History of lactation was self-reported. Electron beam tomography was used to assess coronary and aortic calcification. B-mode ultrasonography was used to assess carotid adventitial diameter, intima–media thickness, and carotid plaque. Multivariable linear and logistic regression models were used to estimate whether lactation was independently associated with markers of subclinical cardiovascular disease. RESULTS: In unadjusted models, compared with mothers who had breastfed all of their children for at least 3 months, mothers who had not breastfed were more likely to have coronary artery calcification (17% compared with 32%), aortic calcification (17% compared with 39%), carotid plaque (10% compared with 18%), and larger carotid adventitial diameters (mean±standard deviation 6.63±0.59 compared with 6.87±0.60 mm). After adjusting for measures of socioeconomic status and lifestyle and family history variables, mothers who had not breastfed remained more likely to have aortic calcification (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.47–10.00) and coronary artery calcification (OR 2.78, 95% CI 1.05–7.14) than mothers who had consistently breastfed. After further adjustment for body mass index and traditional risk factors for cardiovascular disease, mothers who had not breastfed remained more likely to have aortic calcification than mothers who had consistently breastfed (OR 5.26, 95% CI 1.47–20.00). CONCLUSION: Mothers who do not breastfeed their infants seem to be at increased risk of vascular changes associated with future cardiovascular disease. LEVEL OF EVIDENCE: II

Psychotropic medication use and risk of adverse cardiovascular events in women with suspected coronary artery disease: outcomes from the Women’s Ischemia Syndrome Evaluation (WISE) study

Objective: This study investigated the relation between psychotropic medication use and adverse cardiovascular (CV) events in women with symptoms of myocardial ischaemia undergoing coronary angiography. Method: Women enrolled in the Women’s Ischemia Syndrome Evaluation (WISE) were classified into one of four groups according to their reported antidepressant and anxiolytic medication usage at study intake: (1) no medication (n = 352); (2) anxiolytics only (n = 67); (3) antidepressants only (n = 58); and (4) combined antidepressant and anxiolytics (n = 39). Participants were followed prospectively for the development of adverse CV events (for example, hospitalisations for non-fatal myocardial infarction, stroke, congestive heart failure and unstable angina) or all-cause mortality over a median of 5.9 years. Results: Use of antidepressant medication was associated with subsequent CV events (HR 2.16, 95% CI 1.21 to 3.93) and death (HR 2.15, 95% CI 1.16 to 3.98) but baseline anxiolytic use alone did not predict subsequent CV events and death. In a final regression model that included demographics, depression and anxiety symptoms, and risk factors for cardiovascular disease, women in the combined medication group (that is, antidepressants and anxiolytics) had higher risk for CV events (HR 3.98, CI 1.74 to 9.10, p = 0.001 and all-cause mortality (HR 4.70, CI 1.7 to 2.97, p = 0.003) compared to those using neither medication. Kaplan-Meier survival curves indicated that there was a significant difference in mortality among the four medication groups (p = 0.001). Conclusions: These data suggest that factors related to psychotropic medication such as depression refractory to treatment, or medication use itself, are associated with adverse CV events in women with suspected myocardial ischaemia.

Hostility scores are associated with increased risk of cardiovascular events in women undergoing coronary angiography: a report from the NHLBI-Sponsored WISE Study.

Objective: To evaluate hostility-related personality traits assessed by the Cook Medley Hostility Inventory and to relate these to the occurrence of adverse cardiac events in women with suspected myocardial ischemia. Methods: The cohort included 506 women with suspected coronary artery disease from the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study. We examined individual components of the Cook Medley Hostility Score (CMHS) measuring cynicism, hostile affect, and aggressive responding, and a total CMHS (sum of these three) and associations with adverse events (defined as hospitalization for angina, nonfatal myocardial infarction, stroke, congestive heart failure (CHF) other vascular events and death) during 3 to 6 years follow-up using Cox proportional hazard modeling. Results: Women with adverse events had higher total CMHS (10.6 ± 5.5) than women without any of these events (9.2 ± 5.1) p = .02. They also had poorer survival by Kaplan-Meier analysis (log-rank p < .05). Unadjusted Cox models showed that the individual scores of cynicism and aggressive responding and the total CMHS were associated with more adverse events (all p < .05). Women with total CMHS above the median had a 35% increase risk of an adverse event in comparison to women with lower scores. In a risk-adjusted Cox model, the hazard ratio for an adverse event was 1.5 (p = .03) for women with total CMHS above the median. Conclusion: In this cohort of women with suspected myocardial ischemia, higher Cook Medley scores reflecting cynicism, hostile affect, and aggressive responding were associated with poorer 3 to 6 year event-free survival and a higher risk of adverse events. After adjusting for risk factors and CAD, the association with risk for adverse events increased. CAD = coronary artery disease; CHF = congestive heart failure, HT = hormone therapy; WISE = Women’s Ischemia Syndrome Evaluation; CHD = coronary heart disease; MI = myocardial infarction; HERS = Heart and Estrogen/Progestin Replacement Study; NHLBI = National Heart, Lung, and Blood Institute; CMHS = Cook Medley Hostility Score.

Accuracy of maternal recall of gestational weight gain 4 to 12 years after delivery.

There is growing interest in the relationship between gestational weight gain (GWG) and long‐term maternal and child outcomes, yet little is known about the accuracy of long‐term maternal recall of GWG. Our objective was to assess the accuracy of maternal recall of GWG at 4–12 years postpartum (mean, 8 years) compared with medical‐record documented GWG, and compare recalled GWG to documented GWG with respect to their associations with adverse pregnancy outcomes including small for gestational age (SGA) birth, preterm birth, cesarean delivery, and postpartum weight retention (PPWR) (n = 503). Adequacy of recalled and documented GWG was assessed according to the 2009 Institute of Medicine (IOM) guidelines. We observed moderate agreement between documented and maternal self‐reported GWG as continuous variables (r = 0.63, P < 0.01). When recalled GWG was used to categorize women, 45, 53, and 20% of women with inadequate, adequate, and excessive documented GWG were misclassified, respectively. When comparing models fitted with documented or recalled GWG, there were no meaningful differences in associations between inadequate GWG and SGA birth (odds ratio 2.2 (95% confidence interval: 1.3, 3.7) vs. 2.1 (1.2, 3.8), respectively) or excessive GWG and PPWR (2.5 (1.6, 3.9) vs. 2.5 (1.5, 4.0), respectively). However, the use of recalled GWG attenuated associations between inadequate GWG and PPWR (documented: 0.5 (0.3, 0.9) vs. recalled GWG: 1.3 (0.7, 2.3)) and excessive GWG and preterm birth (documented: 2.5 (1.4, 4.5) vs. recalled GWG: 1.5 (0.9, 2.7)). Our data suggest a varying degree of bias when using recalled GWG to study selected adverse outcomes.

Lactation and maternal subclinical cardiovascular disease among premenopausal women

OBJECTIVE The objective of the study was to examine the association between lactation and maternal subclinical cardiovascular disease. STUDY DESIGN The Women and Infants Study of Healthy Hearts enrolled 607 mothers who delivered a singleton between 1997 and 2002. In 2007, participating mothers underwent measurements of carotid intima-media thickness, lumen diameter, adventitial diameter, and carotid-femoral pulse wave velocity. Multivariable linear and logistic regressions were used to estimate the associations between lactation and subclinical cardiovascular disease. RESULTS Compared with mothers who breastfed for 3 or more months after every birth, mothers who never breastfed exhibited a 0.13 mm larger lumen diameter (95% confidence interval, 0.04-0.22) and a 0.12 mm larger adventitial diameter (95% confidence interval, 0.02-0.22) in models adjusting for age, parity, birth outcome, sociodemographic variables, health-related behaviors, family history, gestational weight gain, early adult body mass index, current body mass index, C-reactive protein, blood pressure, cholesterol, triglyceride, high-density lipoprotein, glucose, and insulin levels. CONCLUSION Mothers who do not breastfeed have vascular characteristics associated with a greater risk of cardiovascular disease.

Breastfeeding and Subsequent Maternal Visceral Adiposity

Women gain visceral fat during pregnancy. Studies examining the impact of breastfeeding on maternal body composition are inconclusive. We examined the extent to which breastfeeding was associated with visceral adiposity in a sample of US women. This was a cross‐sectional analysis of 351 women aged 45–58 years, who were free of clinical cardiovascular disease and had not used oral contraceptives or hormone replacement therapy in the 3 months prior to enrollment in the Study of Womens Health Across the Nation (SWAN)‐Heart Study (2001–2003). History of breastfeeding was self‐reported. Computed tomography was used to assess abdominal adiposity. Among premenopausal/early‐peri‐menopausal mothers, those who never breastfed had 28% greater visceral adiposity (95% confidence interval (CI): 11–49, P = 0.001), 4.7% greater waist‐hip ratio (95% CI: 1.9–7.4, P < 0.001), and 6.49 cm greater waist circumference (95% CI: 3.71–9.26, P < 0.001) than mothers who breastfed all of their children for ≥3 months in models adjusting for study site; age; parity; years since last birth; socioeconomic, lifestyle, and family history variables; early adult BMI; and current BMI. In comparison to women who were nulliparous, mothers who breastfed all of their children for ≥3 months had similar amounts of visceral fat (P > 0.05). In contrast, premenopausal/early‐peri‐menopausal mothers who had never breastfed had significantly greater visceral adiposity (42% (95% CI: 17–70), P < 0.001), waist circumference (6.15 cm (95% CI: 2.75–9.56), P < 0.001), and waist‐hip ratio (3.7% (95% CI: 0.69–6.8), P = 0.02) than nulliparous women. No significant relationships were observed among late peri‐menopausal/postmenopausal women. In conclusion, until menopause, mothers who did not breastfeed all of their children for ≥3 months exhibit significantly greater amounts of metabolically active visceral fat than mothers who had breastfed all of their children for ≥3 months.