The Impact of Past and Current Alcohol Consumption Patterns on Progression of Carotid Intima-Media Thickness Among Women and Men Living with HIV Infection.

BACKGROUND: The relationship between alcohol consumption and atherosclerosis has not been sufficiently examined among people living with HIV (PLWH). METHODS: We analyzed data from PLWH in the Women's Interagency HIV Study (WIHS; n = 1,164) and the Multicenter AIDS Cohort Study (MACS; n = 387) with no history of cardiovascular disease (CVD). Repeated measures of intima-media thickness of the right common carotid artery (CCA-IMT) were assessed using B-mode ultrasound from 2004 to 2013. Current alcohol consumption was collected at time of CCA-IMT measurement and was categorized according to gender-specific weekly limits. Group-based trajectory models categorized participants into past 10-year consumption patterns (1994 to 2004). Multivariate generalized estimating equations were conducted to assess the association of past and current alcohol use patterns on change in CCA-IMT by cohort, controlling for age, race, cigarette and illicit drug use, probable depression, HIV RNA viral load, antiretroviral therapy exposure, and hepatitis C coinfection. RESULTS: Among the WIHS, past heavy alcohol consumption was associated with increased CCA-IMT level over time (ß = 8.08, CI 0.35, 15.8, p = 0.04), compared to abstinence. Among the MACS, compared to abstinence, all past consumption patterns were associated with increased CCA-IMT over time (past low: ß = 15.3, 95% CI 6.46, 24.2, p < 0.001; past moderate: ß = 14.3, CI 1.36, 27.2, p = 0.03; past heavy: ß = 21.8, CI 4.63, 38.9, p = 0.01). Current heavy consumption was associated with decreased CCA-IMT among the WIHS (ß = -11.4, 95% CI -20.2, -2.63, p = 0.01) and MACS (ß = -15.4, 95% CI -30.7, -0.13, p = 0.04). No statistically significant time by consumption pattern effects were found. CONCLUSIONS: In both cohorts, 10-year heavy consumption was associated with statistically significant increases in carotid artery thickness, compared to abstinence. Long-term patterns of drinking at any level above abstinence were particularly significant for increases in IMT among men, with heavy consumption presenting with the greatest increase. Our results suggest a potentially different window of risk among past and current heavy drinkers. Further studies are needed to determine whether alcohol consumption level is associated with intermediate measures of atherosclerosis. Alcohol screening and interventions to reduce heavy consumption may benefit PLWH who are at risk of CVD.

Inflammatory response to mental stress and mental stress induced myocardial ischemia.

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. METHODS: Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. RESULTS: Of 607 patients analyzed in this study, (mean age 63 ±â€¯9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p <0.0001), but not hsCRP. However, the changes in these markers were similar in those with and without MSIMI. Neither resting levels of these biomarkers, nor their changes with mental stress were significantly associated with MSIMI. Results in the replication sample were similar. CONCLUSION: Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI.

Myocardial ischemia and angiotensin-converting enzyme inhibition: comparison of ischemia during mental and physical stress.

OBJECTIVE: Mental stress provokes myocardial ischemia in many patients with stable coronary artery disease (CAD). Mental stress-induced myocardial ischemia (MSIMI) portends a worse prognosis, independent of standard cardiac risk factors or outcome of traditional physical stress testing. Angiotensin II plays a significant role in the physiological response to stress, but its role in MSIMI remains unknown. Our aim was to evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) is associated with a differential effect on the incidence of MSIMI compared with ischemia during physical stress. METHODS: Retrospective analysis of 218 patients with stable CAD, including 110 on ACEI, was performed. 99m-Tc-sestamibi myocardial perfusion imaging was used to define ischemia during mental stress, induced by a standardized public speaking task, and during physical stress, induced by either exercise or adenosine. RESULTS: Overall, 40 patients (18%) developed MSIMI and 80 patients (37%) developed ischemia during physical stress. MSIMI occurred less frequently in patients receiving ACEIs (13%) compared with those not on ACEIs (24%; p = .030, adjusted odds ratio = 0.42, 95% confidence interval = 0.19-0.91). In contrast, the frequency of myocardial ischemia during physical stress testing was similar in both groups (39% versus 35% in those on and not on ACEIs, respectively); adjusted odds ratio = 0.91, 95% confidence interval = 0.48-1.73). CONCLUSION: In this retrospective study, patients using ACEI therapy displayed less than half the risk of developing ischemia during mental stress but not physical stress. This possible beneficial effect of ACEIs on MSIMI may be contributing to their salutary effects in CAD.

Studying the effects of polycyclic aromatic hydrocarbons on peripheral arterial disease in the United States.

PURPOSE: Polycyclic aromatic hydrocarbons are a group of prevalent pollutants which are produced by incomplete combustion of organic materials such as coal, fuel, tobacco smoking and food cooking. The associations between exposures to polycyclic aromatic hydrocarbons (PAHs) and peripheral arterial disease (PAD) have not been well studied. METHODS: We used the 2001-2004 National Health and Nutrition Examination Survey (NHANES) to investigate the associations between eight monohydroxy urinary metabolites of four PAHs and PAD. RESULTS: In a logistic regression model, subjects within the middle and highest tertiles of fluorene metabolites, 2-hydroxyfluorene (2-FLUO) and 3-hydroxyfluorene (3-FLUO), and phenanthrene metabolites, 1-hydroxyphenanthrene (1-PHEN) and 2-hydroxyphenanthrene (2-PHEN), had significantly higher prevalence of PAD as compared to subjects within the lowest tertile after adjusting for cigarette smoking, diabetes mellitus and other covariates (For 2-FLUO, the 3rd tertile: OR=2.22, 95% CI=1.13-4.37, p for trend=0.02; For 3-FLUO, the 3rd tertile: OR=2.36, 95% CI: 1.16-4.77, p for trend=0.02; For 1-PHEN, the 3rd tertile: OR=1.84, 95% CI: 1.01-3.37, p for trend=0.04; For 2-PHEN, the 3rd tertile: OR=1.76, 95% CI: 1.07-2.88, p for trend=0.03). CONCLUSIONS: Our findings suggest that exposure to PAHs may increase the risk of PAD. Further studies are necessary to explore the associations between PAHs and PAD.

Major depression and coronary flow reserve detected by positron emission tomography.

BACKGROUND: Major depressive disorder (MDD) is associated with coronary heart disease (CHD), but the mechanisms are unclear. The presence of MDD may increase CHD risk by affecting microvascular circulation. It is also plausible that genetic factors influencing MDD may overlap with those for CHD. We sought to examine the relationship between MDD and coronary flow reserve (CFR), the ratio of maximum flow during stress to flow at rest measured in milliliters per minute per gram of tissue. METHODS: We examined 289 male middle-aged twins, including 106 twins (53 twin pairs) discordant for a lifetime history of MDD and 183 control twins (unrelated to any twins in the experimental group) without MDD. To calculate CFR, we used positron emission tomography with nitrogen 13 ((13)N) ammonia to evaluate myocardial blood flow at rest and after adenosine stress. A standard perfusion defect score was also used to assess myocardial ischemia. RESULTS: There was no difference in myocardial ischemia between twins with and without MDD. Among the dizygotic twin pairs discordant for MDD, the CFR was 14% lower in the twins with MDD than in their brothers without MDD (2.36 vs 2.74) (P = .03). This association was not present in the monozygotic discordant pairs who were genetically matched (2.86 vs 2.64) (P = .19). The zygosity-MDD interaction after adjustment was significant (P = .006). The CFR in the dizygotic twins with MDD was also lower than in the control twins. CONCLUSIONS: Our results provide evidence for a shared genetic pathway between MDD and microvascular dysfunction. Common pathophysiologic processes may link MDD and early atherosclerosis.

The joint impact of smoking and exercise capacity on clinical outcomes among women with suspected myocardial ischemia: the WISE study.

BACKGROUND: Although extensive research has been conducted on both smoking and low exercise capacity alone, few studies have examined the joint impact or interaction of these two risk factors. We examined the joint and interactive effects of smoking and self-reported exercise capacity on subsequent clinical events (heart failure, myocardial infarction [MI], stroke, and cardiovascular-related mortality) among women with suspected myocardial ischemia. METHODS: At baseline (1996-1999), 789 women completed angiographic testing of coronary artery disease (CAD) severity and provided self-report information about their smoking history and exercise capacity as well as demographic and other risk factor data. Incidence of clinical events among the women was tracked for a median of 5.9 years; this analysis was conducted in 2008. RESULTS: In an adjusted survival analysis, women with a positive smoking history and self-reported low exercise capacity had the greatest risk of experiencing a clinical event (HR = 7.7, 95% CI 2.3, 25.5), followed by women with a positive smoking history and self-reported high exercise capacity (HR = 6.9, 95% CI 2.0, 24.6) and those with a negative smoking history and self-reported low exercise capacity (HR = 4.9, 95% CI 1.5, 15.8), relative to women with a negative smoking history and self-reported high exercise capacity. Additional analyses revealed a significant interaction between smoking history and exercise capacity, such that (1) women with a positive smoking history did not experience an additional significantly greater risk due to low exercise capacity, unlike those with a negative smoking history, and (2) all women experienced a significantly greater risk due to a positive smoking history regardless of their exercise capacity. CONCLUSIONS: Among women with suspected myocardial ischemia, the combined protective health effects of self-reported high exercise capacity and a negative smoking history remained significant after controlling for preexisting CAD severity and other established risk factors. These findings highlight the importance of studying behavioral risk factors in combination.

Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association.

Depression is commonly present in patients with coronary heart disease (CHD) and is independently associated with increased cardiovascular morbidity and mortality. Screening tests for depressive symptoms should be applied to identify patients who may require further assessment and treatment. This multispecialty consensus document reviews the evidence linking depression with CHD and provides recommendations for healthcare providers for the assessment, referral, and treatment of depression.

Variability of myocardial ischemic responses to mental versus exercise or adenosine stress in patients with coronary artery disease.

BACKGROUND: Mental stress precipitates myocardial ischemia in a significant percentage of coronary artery disease (CAD) patients. Exercise or adenosine stresses produce different physiologic responses and cause myocardial ischemia via different mechanisms. Little is known about the comparative severity and location of myocardial ischemia provoked by these different stressors. In this study we sought to compare the within-individual ischemic responses to mental versus exercise or adenosine stress in a cohort of CAD patients. METHODS AND RESULTS: All patients underwent mental stress and either exercise or adenosine testing within a 1-week period. Mental stress was induced via a public speaking task. Rest-stress myocardial perfusion imaging was used with all testing protocols. Participants were 187 patients (65 women [35%]) with a documented history of CAD and a mean age of 64 +/- 9 years. Mental stress-induced myocardial ischemia (MSIMI) was less prevalent and frequently of less magnitude than exercise- or adenosine-induced ischemia. Ischemia induced by exercise or adenosine testing did not accurately predict the development or the location of MSIMI. The overall concordance between these stressors for provoking ischemia was weak (percent agreement, 71%; kappa [+/- SE], 0.26 +/- 0.07). In a minority of patients (11%) mental stress provoked ischemia in the absence of exercise- or adenosine-induced ischemia. Moreover, in patients who had myocardial ischemia during both stressors, there were significant within-individual differences in the coronary artery distribution of the ischemic regions. MSIMI was more likely to occur in a single-vessel distribution (86%) compared with exercise- or adenosine-induced ischemia (54%). The stressors had moderate agreement if the ischemic region was in the right coronary artery territory (percent agreement, 76%; kappa, 0.52 +/- 0.19) or the left anterior descending coronary artery (percent agreement, 76%; kappa, 0.51 +/- 0.19) and significantly lower agreement in the left circumflex territory (percent agreement, 62%; kappa, 0.22 +/- 0.18). CONCLUSIONS: Our findings indicate that mental and exercise or adenosine stresses provoke different myocardial ischemic responses. These observations suggest that exercise or adenosine testing may not adequately assess the likelihood of occurrence or severity of MSIMI and that different mechanisms are operative in each condition.

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 > or =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.

Depression, inflammation, and incident cardiovascular disease in women with suspected coronary ischemia: the National Heart, Lung, and Blood Institute-sponsored WISE study.

OBJECTIVES: The purpose of this study was to examine prospectively whether inflammation explains the relationship between depression and cardiovascular disease (CVD). BACKGROUND: It is unclear whether inflammation is a mechanism linking depression to CVD. METHODS: We measured C-reactive protein (CRP) and interleukin (IL)-6 in 559 women with suspected coronary ischemia who completed the Beck Depression Inventory (BDI) at baseline and were followed over 5.9 years. We considered indicators of past and current depression to classify women into 3 groups: 1) depression, having both elevated depressive symptoms (BDI > or =10) and a previous diagnosis of depression requiring treatment; 2) possible depression, having either indicator but not both; and 3) no depression, having neither indicator of depression. The main outcome was incidence of CVD events (hospital stays for nonfatal myocardial infarction, stroke, congestive heart failure, and CVD-related mortality). RESULTS: Compared with women without depression, women with depression had a 70% higher CRP (p = 0.0008) and a 25% higher IL-6 (p = 0.04), whereas women with possible depression had 30% higher CRP (p = 0.02) and 28% higher IL-6 (p = 0.01). Depression was a significant predictor of CVD (hazard ratio 2.58, p = 0.0009), but possible depression was not (hazard ratio 1.12, p = 0.68). Adjustment for other patient factors did not substantially affect the results. Addition of CRP decreased the estimate for depression by 13% and addition of IL-6 decreased it by 4%. Both depression and inflammatory biomarkers remained independent predictors of outcome. CONCLUSIONS: Despite their robust association with depression, inflammatory biomarkers explain only a small portion of the association between depression and CVD incidence.

Do men and women differ on measures of mental stress-induced ischemia?

OBJECTIVE: To consider the effects of gender on ischemia in a larger sample, with broadly defined coronary artery disease (CAD). Mental stress has been shown to cause transient myocardial ischemia in a significant percentage of people with CAD. However, little is known about the effects of mental stress on ischemic processes in women. Most studies to date either had few women or required a positive exercise stress test. METHODS: Participants (61 women, 93 men; average age = 63 years) had documented CAD (positive stress test, abnormal catheterization even with minimal disease, or previous myocardial infarction). They underwent mental stress testing and radionuclide perfusion imaging (stress/ rest). Cardiac function data were collected and stress was compared with baseline. The data were then submitted to a series of analyses of variance. RESULTS: A total of 50 (32%) participants exhibited reversible ischemia post psychological stress. This reflects a relative rate of 33% (n = 31 of 93) for men and 31% (n = 19 of 61) for women. No difference between men and women were observed on any measure of hemodynamic functioning (blood pressure, heart rate, or cardiac perfusion). CONCLUSIONS: Results of this study showed no significant differences between men and women on measures of hemodynamic functioning or cardiac perfusion.

Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute Working Group Report.

OBJECTIVE: The National Heart, Lung, and Blood Institute convened an interdisciplinary working group of experts to develop recommendations for the assessment and treatment of depression in patients with coronary heart disease (CHD). METHOD: Consensus of experts. RESULTS: Our current recommendations are that the Beck Depression Inventory-I be employed for epidemiological studies of depression and CHD, that the Patient Health Questionnaire 2-item version be employed for screening for trial eligibility, that the Depression Interview and Structured Hamilton (DISH) be employed for diagnostic ascertainment for trial inclusion, and that the Hamilton rating scale, which is part of the DISH, be employed for both depression symptom reduction and the remission criterion in any trial. We further recommend that a randomized controlled trial be undertaken to determine whether selective serotonin reuptake inhibitors, psychotherapy, or combined treatment can reduce the risk of CHD events and mortality associated with depression in CHD patients. CONCLUSIONS: This report summarizes the recommendations made by the working group and discusses the rationale for each recommendation, the strengths and weaknesses of alternative approaches to assessment and treatment, and the implications for future research in this area.

Mental stress provokes ischemia in coronary artery disease subjects without exercise- or adenosine-induced ischemia.

OBJECTIVES: The purpose of this study was to investigate the possibility that some patients with coronary artery disease (CAD) but negative exercise or chemical stress test results might have mental stress-induced ischemia. The study population consisted solely of those with negative test results. BACKGROUND: Mental stress-induced ischemia has been reported in 20% to 70% of CAD subjects with exercise-induced ischemia. Because mechanisms of exercise and mental stress-induced ischemia may differ, we studied whether mental stress would produce ischemia in a proportion of subjects with CAD who have no inducible ischemia with exercise or pharmacologic tests. METHODS: Twenty-one subjects (14 men, 7 women) with a mean age of 67 years and with a documented history of CAD were studied. All subjects had a recent negative nuclear stress test result (exercise or chemical). Subjects completed a speaking task involving role playing a difficult interpersonal situation. A total of 30 mCi 99mTc-sestamibi was injected at one minute into the speech, and imaging was started 40 min later. A resting image obtained within one week was compared with the stress image. Images were analyzed for number and severity of perfusion defects. The summed difference score based on the difference between summed stress and rest scores was calculated. Severity was assessed using a semiquantitative scoring method from zero to four. RESULTS: Six of 21 (29%) subjects demonstrated reversible ischemia (summed difference score > or =3) with mental stress. No subject had chest pain or electrocardiographic changes during the stressor. Mean systolic and diastolic blood pressure and heart rate all increased between resting and times of peak stress. CONCLUSIONS: Mental stress may produce ischemia in some subjects with CAD and negative exercise or chemical nuclear stress test results.

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Pharmacological treatment of patients with peripheral arterial disease.

Atherosclerosis is a disease process that affects the coronary, cerebral and peripheral arterial circulation. While great emphasis has been placed on the aggressive pharmacological management of coronary artery disease, less attention has been paid to the pharmacological management of peripheral vascular disease, despite its significant morbidity and mortality. The purpose of medical management in peripheral arterial disease is to relieve symptoms of claudication and to prevent thrombotic vascular events. These goals are best achieved through aggressive risk factor modification and pharmacotherapy. Risk factor modification includes smoking cessation, adequate control of blood pressure and cholesterol, as well as aggressive glycaemic control in patients with diabetes mellitus. Antiplatelet therapy and relief of claudication is also achieved through pharmacotherapy. With aggressive risk factor modification and adequate pharmacotherapy, patients with peripheral arterial disease can have an improved quality of life as well as prolonged survival.

Detection and reproducibility of mental stress-induced myocardial ischemia with Tc-99m sestamibi SPECT in normal and coronary artery disease populations.

BACKGROUND: Mental stress-induced ischemia, as detected by radionuclide studies, has yielded reversible ischemia in only 30% to 60% of patients with exercise-induced ischemia. Little is known about the reproducibility of myocardial perfusion imaging in detecting mental stress-induced ischemia. The purpose of this study was to further evaluate the occurrence and reproducibility of mental stress-induced ischemia in patients with coronary artery disease (CAD) and in normal control subjects with a low likelihood of CAD by using sestamibi single photon emission computed tomography (SPECT) imaging. METHODS AND RESULTS: A total of 40 patients were enrolled in this study: 19 patients with CAD and typical angina or reversible ischemia (positive exercise treadmill study or positive adenosine thallium study) and 21 normal control subjects underwent mental stress testing as well as myocardial perfusion imaging. The subjects were given a speaking task, and SPECT imaging was subsequently performed. Two experienced readers compared mental stress imaging with a resting image using a 20-segment cardiac model. Hemodynamic changes in blood pressure and heart rate with mental stress were also measured in all subjects. Each patient with CAD also underwent repeat mental stress testing and myocardial imaging approximately 2 weeks later. Of the 19 patients with CAD and typical angina or with evidence of reversible ischemia, 16 (84%) demonstrated ischemia with mental stress, as detected by sestamibi SPECT imaging. The mean number of new or worsened perfusion defects attributable to mental stress was 3.5, with a mean severity of 1.7. These results were also reproducible. With repeated mental stress testing and myocardial imaging, 12 of the 16 CAD patients (75%) demonstrated evidence of myocardial ischemia. None of the 21 normal control subjects had evidence of mental stress-induced myocardial ischemia. Mental stress also induced reproducible and significant hemodynamic changes in CAD patients. CONCLUSIONS: In patients with known CAD with typical angina or with evidence of reversible ischemia despite taking medications, mental stress was very effective in inducing myocardial ischemia, as detected by sestamibi SPECT imaging. Mental stress was also found to elicit significant hemodynamic responses. Furthermore, these findings demonstrated good reproducibility.

Walking compared with vigorous exercise for the prevention of cardiovascular events in women.

BACKGROUND: The role of walking, as compared with vigorous exercise, in the prevention of cardiovascular disease remains controversial. Data for women who are members of minority racial or ethnic groups are particularly sparse. METHODS: We prospectively examined the total physical-activity score, walking, vigorous exercise, and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women's Health Initiative Observational Study. At base line, participants were free of diagnosed cardiovascular disease and cancer, and all participants completed detailed questionnaires about physical activity. We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events. RESULTS: An increasing physical-activity score had a strong, graded, inverse association with the risk of both coronary events and total cardiovascular events. There were similar findings among white women and black women. Women in increasing quintiles of energy expenditure measured in metabolic equivalents (the MET score) had age-adjusted relative risks of coronary events of 1.00, 0.73, 0.69, 0.68, and 0.47, respectively (P for trend, <0.001). In multivariate analyses, the inverse gradient between the total MET score and the risk of cardiovascular events remained strong (adjusted relative risks for increasing quintiles, 1.00, 0.89, 0.81, 0.78, and 0.72, respectively; P for trend <0.001). Walking and vigorous exercise were associated with similar risk reductions, and the results did not vary substantially according to race, age, or body-mass index. A brisker walking pace and fewer hours spent sitting daily also predicted lower risk. CONCLUSIONS: These prospective data indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women, irrespective of race or ethnic group, age, and body-mass index. Prolonged sitting predicts increased cardiovascular risk.