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Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in aging adults across the United States. Prior studies indicate that the presence of atherosclerosis, the pathogenic basis of CVD, is linked with dementias. Alzheimer's disease (AD) and AD-related dementias are a major public health challenge in the United States. Recent studies indicate that ≈3.7 million Americans ≥65 years of age had clinical AD in 2017, with projected increases to 9.3 million by 2060. Treatment options for AD remain limited. Development of disease-modifying therapies are challenging due, in part, to the long preclinical window of AD. The preclinical incubation period of AD starts in midlife, providing a critical window for identification and optimization of AD risk factors. Studies link AD with CVD risk factors such as hypertension, inflammation, and dyslipidemia. Both AD and CVD are progressive diseases with decades-long development periods. CVD can clinically manifest several years earlier than AD, making CVD and its risk factors a potential predictor of future AD. The current review focuses on the state of literature on molecular and metabolic pathways modulating the heart-brain axis underlying the potential association of midlife CVD risk factors and their effect on AD and related dementias. Further, we explore potential CVD/dementia preventive strategies during the window of opportunity in midlife and the future of research in the field in the multiomics and novel biomarker use era.

Background: Long-term exposure to pollution has been shown to increase risk of cardiovascular disease (CVD) and mortality, and may contribute to the increased risk of CVD among individuals with higher social risk., Methods: Data from the community-based Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were used to quantify Cumulative Social Risk (CSR) by assigning a score of 1 for the presence of each of 4 social risk factors: racial minority, single living, low income, and low educational status. 1-year average air pollution exposure to PM 2.5 was estimated using land-use regression models. Associations with clinical outcomes were assessed using Cox models, adjusting for traditional CVD risk factors. The primary clinical outcome was combined all-cause mortality and nonfatal CVD events., Results: Data were available on 1933 participants (mean age 59 years, 66% female, 44% Black). In a median follow up time of 8.3 years, 137 primary clinical outcome events occurred. PM 2.5 exposure increased with higher CSR score. PM 2.5 was independently associated with clinical outcome (adjusted hazard ratio [HR]: 1.19 [95% CI: 1.00, 1.41]). Participants with ≥2 CSR factors had an adjusted HR of 2.34 (1.48-3.68) compared to those with CSR = 0. The association was attenuated after accounting for PM 2.5 (HR: 2.16; [1.34, 3.49]). Mediation analyses indicate that PM 2.5 explained 13% of the risk of clinical outcome in individuals with CSR score ≥ 2., Conclusion: In a community-based cohort study, we found that the association of increasing CSR with higher CVD and mortality risks is partially accounted for by exposure to PM 2.5 environmental pollutants.

Background: Ideal cardiovascular health (CVH) was proposed by the American Heart Association to promote population health. We aimed to characterize the association between ideal CVH and markers of subclinical cardiovascular disease (CVD)., Hypothesis: We hypothesized that ideal CVH is associated with several markers of subclinical CVD., Methods: We used data from the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. We assigned 1 for each of the ideal CVH factors met. Endothelial function, expressed as Framingham reactive hyperemia index (fRHI), was measured using the EndoPAT device. Coronary artery calcium (CAC) and carotid intima-media thickness (CIMT) were quantified using electron beam computed tomography and carotid ultrasonography, respectively., Results: A total of 1933 participants (mean [SD] age: 59 [7.5] years, 34% male, 44% black) were included. The mean number of ideal CVH factors met was 2.3 ± 1.3, with blacks having significantly lower score compared to whites (2.0 ± 1.2 vs 2.5 ± 1.4, respectively; P < 0.001). Seven hundred and eighty-nine participants (41%) achieved ≥3 ideal CVH factors. Participants with ≥3 ideal CVH factors (compared to those with <3 factors) had an average of 107 (95% confidence interval [CI]: 50-165) Agatston units lower CAC, 0.04 (0.01-0.06) mm lower CIMT, and 0.07 (0.02-0.12) units higher fRHI, after adjusting for age, sex, race, income, education, and marital status. Participants with ≥3 ideal CVH factors had 50% lower odds (95% CI: 28%-66%) of having CAC >100 Agatston units., Conclusion: In a community-based study with low prevalence of ideal CVH, even achieving three or more ideal CVH factors were associated with lower burden of subclinical CVD, indicating the utility of this construct for disease prevention., (© 2018 Wiley Periodicals, Inc.)

Background: Determination of the correlation of ideal cardiovascular health variables among spousal or cohabitating partners may guide the development of couple-based interventions to reduce cardiovascular disease risk., Method and Results: We used data from the HeartSCORE (Heart Strategies Concentrating on Risk Evaluation) study. Ideal cardiovascular health, defined by the American Heart Association, comprises nonsmoking, body mass index <25 kg/m 2 , physical activity at goal, diet consistent with guidelines, untreated total cholesterol <200 mg/dL, untreated blood pressure <120/80 mm Hg, and untreated fasting glucose <100 mg/dL. McNemar test and logistic regression were used to assess concordance patterns in these variables among partners (ie, concordance in achieving ideal factor status, concordance in not achieving ideal factor status, or discordance-only one partner achieving ideal factor status). Overall, there was a low prevalence of ideal cardiovascular health among the 231 couples studied (median age 61 years, 78% white). The highest concordances in achieving ideal factor status were for nonsmoking (26.1%), ideal fruit and vegetable consumption (23.9%), and ideal fasting blood glucose (35.6%). The strongest odds of intracouple concordance were for smoking (odds ratio, 3.6; 95% confidence interval, 1.9-6.5), fruit and vegetable consumption (odds ratio, 4.8; 95% confidence interval, 2.5-9.3) and blood pressure (odds ratio, 3.0; 95% confidence interval, 1.2-7.9). A participant had 3-fold higher odds of attaining ≥3 ideal cardiovascular health variables if he or she had a partner who attained ≥3 components (odds ratio 3.0; 95% confidence interval, 1.6-5.6)., Conclusions: Intracouple concordance of ideal cardiovascular health variables supports the development and testing of couple-based interventions to promote cardiovascular health. Fruit and vegetable consumption and smoking may be particularly good intervention targets., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: We aimed to assess racial differences in air pollution exposures to ambient fine particulate matter (particles with median aerodynamic diameter <2.5 µm [PM 2.5 ]) and black carbon (BC) and their association with cardiovascular disease (CVD) risk factors, arterial endothelial function, incident CVD events, and all-cause mortality., Approach and Results: Data from the HeartSCORE study (Heart Strategies Concentrating on Risk Evaluation) were used to estimate 1-year average air pollution exposure to PM 2.5 and BC using land use regression models. Correlates of PM 2.5 and BC were assessed using linear regression models. Associations with clinical outcomes were determined using Cox proportional hazards models, adjusting for traditional CVD risk factors. Data were available on 1717 participants (66% women; 45% blacks; 59±8 years). Blacks had significantly higher exposure to PM 2.5 (mean 16.1±0.75 versus 15.7±0.73µg/m 3 ; P =0.001) and BC (1.19±0.11 versus 1.16±0.13abs; P =0.001) compared with whites. Exposure to PM 2.5 , but not BC, was independently associated with higher blood glucose and worse arterial endothelial function. PM 2.5 was associated with a higher risk of incident CVD events and all-cause mortality combined for median follow-up of 8.3 years. Blacks had 1.45 (95% CI, 1.00-2.09) higher risk of combined CVD events and all-cause mortality than whites in models adjusted for relevant covariates. This association was modestly attenuated with adjustment for PM 2.5 ., Conclusions: PM 2.5 exposure was associated with elevated blood glucose, worse endothelial function, and incident CVD events and all-cause mortality. Blacks had a higher rate of incident CVD events and all-cause mortality than whites that was only partly explained by higher exposure to PM 2.5 ., (© 2018 American Heart Association, Inc.)

Background: The association between migraine headache and cardiovascular events has been inconsistent. This study determines the long-term risk of cardiovascular events among women with and without a history of migraine headache who were under evaluation for suspected myocardial ischemia in the Women's Ischemia Syndrome Evaluation (WISE)., Methods: The WISE is a National Heart, Lung and Blood Institute-sponsored prospective, multicenter study that aims to improve myocardial ischemia evaluation in women. A total of 936 women presenting with symptoms of myocardial ischemia underwent structured data collection and coronary angiography. Information pertaining to migraine headache was available in 917 women. All-cause mortality data were available on all women for a median of 9.5 years, and nonfatal cardiovascular event data were available on 888 women for a median of 6.5 years., Results: A total of 224 (24.4%) women reported a history of migraine headache. Compared with women who did not report a history of migraine headache, women with a history of migraine headache had an increased adjusted risk of cardiovascular event (cardiovascular death, nonfatal myocardial infarction, heart failure, or stroke) (hazard ratio 1.83; 95% confidence interval, 1.22-2.75) at a median follow-up of 6.5 years. This result was driven mainly by a twofold increase in the risk of stroke (hazard ratio 2.33; 95% confidence interval, 1.16-4.68)., Conclusion: Among women being evaluated for ischemic heart disease, those reporting a history of migraine headache had increased risk of future cardiovascular events on long-term follow-up. This risk was primarily driven by a more-than twofold increase in the risk of stroke., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Quantifying the cumulative effect of social risk factors on cardiovascular disease (CVD) risk can help to better understand the sources of disparities in health outcomes., Method and Results: Data from the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were used to create an index of cumulative social risk (CSR) and quantify its association with incident CVD and all-cause mortality. CSR was defined by assigning a score of 1 for the presence of each of 4 social factors: i) racial minority status (Black race), ii) single living status, iii) low income, and iv) low educational level. Hazard ratios (HRs) were computed using Cox-regression models, adjusted for CVD risk factors. Over a median follow-up period of 8.3 years, 127 incident events were observed. The incidence of the primary outcome for subgroups of participants with 0, 1, and ≥2 CSR scores was 5.31 (95% CI, 3.40-7.22), 10.32 (7.16-13.49) and 17.80 (12.94-22.67) per 1000 person-years, respectively. Individuals with CSR score of 1 had an adjusted HR of 1.85 (1.15-2.97) for incident primary outcomes, compared to those with score of 0. The corresponding HR for individuals with CSR score of 2 or more was 2.58 (1.60-4.17)., Conclusion: An accumulation of social risk factors independently increased the likelihood of CVD events and deaths in a cohort of White and Black individuals.

Objective: Studies have linked vasomotor symptoms (VMS) to markers of cardiovascular disease (CVD) risk, yet few have considered clinical cardiovascular events. Data suggest that associations may depend upon the age that symptoms occur. We examined associations between VMS and cardiovascular events and endothelial function, considering age of symptom onset., Methods: The Women's Ischemia Syndrome Evaluation enrolled women referred for coronary angiography for suspected myocardial ischemia. A total of 254 women aged more than 50 years, postmenopausal, with both ovaries, not taking hormone therapy underwent a baseline evaluation, were followed annually (median = 6.0 y), and the National Death Index was searched to ascertain CVD mortality (median = 9.3 y). A subset of participants underwent brachial artery ultrasound for flow-mediated dilation (FMD). Receiver-operating curve analysis was used to determine vasomotor symptom groups (symptoms beginning < age 42 [early onset], beginning ≥42 [later onset], never) which were examined in relation to cardiovascular events and FMD in Cox proportional hazard and linear regression models., Results: Women reporting early onset VMS (HR = 3.35, 95% CI = 1.23-7.86, P = 0.005) and women who never had VMS (HR = 2.17, 95% CI = 1.02-4.62, P = 0.05) had higher CVD mortality than women with later onset symptoms (multivariable models). Women with early onset VMS had lower FMD than women with later onset symptoms (b = -4.31, SE = 2.10, P = 0.04, multivariable)., Conclusions: Women with signs and symptoms of ischemia who had VMS beginning early in midlife had higher CVD mortality and reduced endothelial function relative to women with later onset symptoms. Future research should evaluate the vascular phenotype of women with early midlife VMS., Competing Interests: G Braunstein is a consultant for Merck (Merck Manual), Takada Pharmaceuticals, Amgen, Allergan, Synagena, Sanofi, and Johnson and Johnson. G Braunstein owns stock in Pfizer and is a part-time employee of Pathway Genomics. F Stanczyk has consulted with Merck & Co., Agile Therapeutics, TherapeuticsMD, and Abbvie. For the remaining authors none were declared.

Background: Women with polycystic ovary syndrome (PCOS) have greater cardiac risk factor clustering but the link with mortality is incompletely described., Objective: To evaluate outcomes in 295 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS., Materials and Methods: A total of 25/295 (8%) women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia, defined as the top quartile of androstenedione (≥701 pg/mL), testosterone (≥30.9 ng/dL), or free testosterone (≥4.5 pg/mL). Cox proportional hazard model estimated death (n = 80)., Results: Women with clinical features of PCOS had an earlier menopause (p = 0.01), were more often smokers (p < 0.04), and trended toward more angiographic coronary artery disease (CAD) (p = 0.07) than women without these features. Cumulative 10-year mortality was 28% for women with (n = 25) versus 27% without clinical features of PCOS (n = 270) (p = 0.85). PCOS was not a significant predictor (p = NS) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD., Conclusion: From this longer-term follow up of a relatively small cohort of postmenopausal women with suspected ischemia, the prevalence of PCOS is similar to the general population, and clinical features of PCOS are not associated with CAD or mortality. These findings question whether identification of clinical features of PCOS in postmenopausal women who already have known cardiovascular disease provides any additional opportunity for risk factor intervention.

Background: The contribution of arterial endothelial dysfunction (ED) to increased cardiovascular disease (CVD) risk among Blacks is not known., Hypothesis: We investigated whether peripheral arterial ED explains racial disparity in CVD events., Methods: Data from the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study was used. Endothelial dysfunction was assessed by the Framingham reactive hyperemia index (fRHI), measured using pulse amplitude tonometry (PAT). Lower values of fRHI indicate more severe ED. The primary outcome of interest was combined CVD events and all-cause mortality., Results: 1454 individuals (62% female, 40% Black, mean age 59 ± 8 years) had available data on fRHI (mean [SD]: 0.74 [0.46]). Over a mean follow-up period of 8.0 ± 2.4 years (11,186 person-years), 116 events were observed. Black race, male sex, smoking, diabetes, blood pressure, triglycerides, C-reactive protein, and interleukin-6 were inversely correlated with fRHI in univariate models. In an unadjusted Cox regression model, fRHI was associated with 20% lower risk of the primary outcome events (hazard ratio [HR] per 1-SD higher fRHI: 0.80, 95% confidence interval [CI]: 0.66-0.97). However, this association was no longer significant after adjustment for CVD risk factors (HR: 0.90, 95% CI: 0.74-1.11). In an age- and sex-adjusted model, Blacks had 1.68 (95% CI: 1.16-2.43) higher risk of primary outcome compared with Whites. This association was not significantly attenuated by addition of fRHI to the multivariable models., Conclusion: Black race is associated with increased risk of CVD events and mortality independent of its associations with ED, as measured by PAT., (© 2016 Wiley Periodicals, Inc.)

Objectives: Insomnia and sleep apnea frequently co-occur and are independently associated with an increased risk of cardiovascular disease, but little is known about cardiovascular disease risk among individuals with comorbid insomnia and sleep apnea. The current study examined traditional risk factors and a physiologic biomarker of cardiovascular risk in comorbid insomnia and sleep apnea., Design: Community-based participatory research study., Participants: The sample comprised 795 participants without preexisting cardiovascular disease from the Heart Strategies Concentrating On Risk Evaluation (Heart SCORE) study., Measurements and Results: Participants were assessed for symptoms of insomnia and sleep apnea risk, as well as for presence of obesity, smoking, a sedentary lifestyle, hypertension, dyslipidemia, and diabetes. Baseline resting brachial artery diameter was measured by B-mode ultrasonography. A total of 138 participants (17.4%) met criteria for insomnia syndrome alone, 179 (22.5%) were at high risk for sleep apnea alone, 95 (11.9%) reported both insomnia syndrome and high sleep apnea risk, and 383 (48.2%) reported having neither insomnia nor sleep apnea symptoms Both high sleep apnea risk alone and comorbid insomnia and high sleep apnea risk groups had greater frequencies of obesity, sedentary lifestyle, hypertension, and three or more traditional cardiovascular risk factors and significantly larger brachial artery diameters than the insomnia alone group and those without insomnia or sleep apnea symptoms. No differences in traditional cardiovascular risk factors or brachial artery diameter were found between the high sleep apnea risk and comorbid groups., Conclusions: These findings suggest that sleep apnea is a major contributor to cardiovascular risk and co-occurring insomnia does not appear to add to this risk.

Purpose: To identify factors associated with attrition in a longitudinal study of cardiovascular prevention., Methods: Demographic, clinical, and psychosocial variables potentially associated with attrition were investigated in 1841 subjects enrolled in the southwestern Pennsylvania Heart Strategies Concentrating on Risk Evaluation study. Attrition was defined as study withdrawal, loss to follow-up, or missing 50% or more of study visits., Results: Over 4 years of follow-up, 291 subjects (15.8%) met criteria for attrition. In multivariable regression models, factors that were independently associated with attrition were black race (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.55-3.16; P < .001), younger age (OR per 5-year increment, 0.88; 95% CI, 0.79-0.99; P < .05), male gender (OR, 1.79; 95% CI, 1.27-2.54; P < .05), no health insurance (OR, 2.04; 95% CI, 1.20-3.47; P < .05), obesity (OR, 1.80; 95% CI, 1.07-3.02; P < .05), CES-D depression score 16 or higher (OR, 2.02; 95% CI, 1.29-3.19; P < .05), and higher ongoing life events questionnaire score (OR, 1.09; 95% CI, 1.04-1.13; P < .001). Having a spouse/partner participating in the study was associated with lower odds of attrition (OR, 0.60; 95% CI, 0.37-0.97; P < .05). A synergistic interaction was identified between black race and depression., Conclusions: Attrition over 4 years was influenced by sociodemographic, clinical, and psychological factors that can be readily identified at study entry. Recruitment and retention strategies targeting these factors may improve participant follow-up in longitudinal cardiovascular prevention studies., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Large epidemiologic studies examining differences in cardiovascular disease (CVD) risk factor profiles between European Americans and African Americans have exclusively used self-identified race (SIR) to classify individuals. Recent genetic epidemiology studies of some CVD risk factors have suggested that biogeographic ancestry (BGA) may be a better predictor of CVD risk than SIR. This hypothesis was investigated in 464 African Americans and 771 European Americans enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) Study in March and April 2010. Individual West African and European BGA were ascertained by means of a panel of 1,595 genetic ancestry informative markers. Individual BGA varied significantly among African Americans and to a lesser extent among European Americans. In the total cohort, BGA was not found to be a better predictor of CVD risk factors than SIR. Both measures predicted differences in the presence of the metabolic syndrome, waist circumference, triglycerides, body mass index, very low density lipoprotein cholesterol, lipoprotein A, and systolic and diastolic blood pressure between European Americans and African Americans. These results suggest that for most nongenetic cardiovascular epidemiology studies, SIR is sufficient for predicting CVD risk factor differences between European Americans and African Americans. However, higher body mass index and diastolic blood pressure were significantly associated with West African BGA among African Americans, suggesting that BGA should be considered in genetic cardiovascular epidemiology studies carried out among African Americans.

Background: Sleep complaints are highly prevalent and associated with cardiovascular disease (CVD) morbidity and mortality. This is the first prospective study to report the association between commonly reported sleep symptoms and the development of the metabolic syndrome, a key CVD risk factor., Methods: Participants were from the community-based Heart Strategies Concentrating on Risk Evaluation study. The sample was comprised of 812 participants (36% African American; 67% female) who were free of metabolic syndrome at baseline, had completed a baseline sleep questionnaire, and had metabolic syndrome evaluated 3 years after baseline. Apnea-hypopnea index (AHI) was measured cross-sectionally using a portable monitor in a subset of 290 participants. Logistic regression examined the risk of developing metabolic syndrome and its components according to individual sleep symptoms and insomnia syndrome., Results: Specific symptoms of insomnia (difficulty falling asleep [DFA] and "unrefreshing" sleep), but not a syndromal definition of insomnia, were significant predictors of the development of metabolic syndrome. Loud snoring more than doubled the risk of developing the metabolic syndrome and also predicted specific metabolic abnormalities (hyperglycemia and low high-density lipoprotein cholesterol). With further adjustment for AHI or the number of metabolic abnormalities at baseline, loud snoring remained a significant predictor of metabolic syndrome, whereas DFA and unrefreshing sleep were reduced to marginal significance., Conclusion: Difficulty falling asleep, unrefreshing sleep, and, particularly, loud snoring, predicted the development of metabolic syndrome in community adults. Evaluating sleep symptoms can help identify individuals at risk for developing metabolic syndrome.

Study Objectives: To evaluate the relations between sleep characteristics and cardiovascular risk factors and napping behavior, and to assess whether daytime napping leads to subsequent better or worse sleep., Methods: The sample consisted of 224 (African American, Caucasian, and Asian) middle-aged men and women. Sleep measures included nine nights of actigraphy and sleep diaries, sleep questionnaires, and one night of polysomnography to measure sleep disordered breathing., Results: More frequent napping was associated with shorter nighttime sleep duration averaged across the nine nights of actigraphy (especially among African Americans), more daytime sleepiness, more pain and fatigue by diary, and increased body mass index and waist circumference. Shorter nighttime sleep duration was associated with taking a nap during the next day and taking a nap was associated with less efficient sleep the next night., Conclusions: Napping in middle-aged men and women is associated with overall less nighttime sleep in African Americans and lower sleep efficiency as measured by actigraphy, and increased BMI and central adiposity. These findings point to the importance of measuring of napping in understanding associations of sleep with cardiovascular risk.

Background: For women, who are more likely to live in poverty, defining the clinical and economic impact of socioeconomic factors may aid in defining redistributive policies to improve healthcare quality., Methods: The NIH-NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) enrolled 819 women referred for clinically indicated coronary angiography. This study's primary end point was to evaluate the independent contribution of socioeconomic factors on the estimation of time to cardiovascular death or myocardial infarction (MI) (n = 79) using Cox proportional hazards models. Secondary aims included an examination of cardiovascular costs and quality of life within socioeconomic subsets of women., Results: In univariable models, socioeconomic factors associated with an elevated risk of cardiovascular death or MI included an annual household income <$20,000 (p = 0.0001), <9th grade education (p = 0.002), being African American, Hispanic, Asian, or American Indian (p = 0.016), on Medicaid, Medicare, or other public health insurance (p < 0.0001), unmarried (p = 0.001), unemployed or employed part-time (p < 0.0001), and working in a service job (p = 0.003). Of these socioeconomic factors, income (p = 0.006) remained a significant predictor of cardiovascular death or MI in risk-adjusted models that controlled for angiographic coronary disease, chest pain symptoms, and cardiac risk factors. Low-income women, with an annual household income <$20,000, were more often uninsured or on public insurance (p < 0.0001) yet had the highest 5-year hospitalization and drug treatment costs (p < 0.0001). Only 17% of low-income women had prescription drug coverage (vs. >or=50% of higher-income households, p < 0.0001), and 64% required >or=2 anti-ischemic medications during follow-up (compared with 45% of those earning >or=$50,000, p < 0.0001)., Conclusions: Economic disadvantage prominently affects cardiovascular disease outcomes for women with chest pain symptoms. These results further support a profound intertwining between poverty and poor health. Cardiovascular disease management strategies should focus on policies that track unmet healthcare needs and worsening clinical status for low-income women.

Background: Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described., Objective: The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS., Methods: A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (> or = 701 pg/ml), testosterone (> or = 30.9 ng/dl), or free testosterone (> or = 4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55)., Results: Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates., Conclusion: Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.

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.

Objectives: Atherosclerotic cardiovascular disease is the leading cause of death in the United States. Atherosclerosis begins early in life; however, children and young and middle-aged adults are not universally screened for the presence of modifiable cardiovascular disease risk factors. The purpose of this study was to investigate whether cardiovascular disease risk-factor assessment in children can identify families who are at increased risk for cardiovascular disease., Participants and Methods: Family Strategies Concentrating on Risk Evaluation is a community-based participatory research study designed to stratify cardiovascular disease risk in a cohort of children and their parents. Eligible families, consisting of > or = 1 child and > or = 1 biological parent, are recruited through community and faith-based educational and screening programs. In a single, fasted study visit, participants undergo assessment of cardiovascular disease risk factors: obesity, hypertension, dyslipidemia, and metabolic syndrome. Associations of cardiovascular disease risk factors between children and their parents were assessed., Results: Data were analyzed from 94 families: 108 parents (mean age: 38.5 +/- 7.5 years), 141 children (mean age: 10.5 +/- 3.4 years), and 170 child-parent pairs. Child-parent association was strong for many risk factors: BMI, waist circumference, systolic blood pressure, triglycerides, and total cholesterol. Several discrete-defined risk factors in children were found to be significant predictors of the presence of the same risk factors in their parents. Parents of children with hypertension, obesity, or hypertriglyceridemia had 15 times, 6 times, or 5 times increased odds, respectively, of having the same risk factors., Conclusions: Identification of several clinically apparent and silent cardiovascular disease risk factors in children predicts elevated cardiovascular disease risk in their parents. Because children access primary care more frequently than adults, children can potentially serve as the index case to identify families at increased risk for cardiovascular disease.

Aims: Women with chest pain but without obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular (CV) events, but half continue to experience debilitating chest pain over many years. This study compared CV outcomes in women with persistent chest pain (PChP) vs. those without PChP., Methods and Results: We studied 673 Women's Ischaemia Syndrome Evaluation (WISE) participants with chest pain undergoing coronary angiography for suspected myocardial ischaemia and at least 1 year of follow-up. PChP was defined as self-reported continuing chest pain after 1 year. Events occurring after that year were recorded for a median of 5.2 years. We compared CV event rates for women with and without PChP in subgroups with and without obstructive CAD. The median age was 58 years, 20% were racial minorities, 45% had PChP, 39% had obstructive CAD. Among women without CAD, those with PChP had more than twice the rate of composite CV events (P = 0.03), that included non-fatal myocardial infarctions (P = 0.11), strokes (P = 0.03), congestive heart failure (P = 0.38), and CV deaths (P = 0.73), compared with those without PChP. In women with CAD, there was no difference in composite CV events in those with and without PChP (P = 0.72)., Conclusion: Among women undergoing coronary angiography for suspected myocardial ischaemia, PChP in women with no obstructive CAD predicted adverse CV outcomes. Such women might benefit from additional evaluation and aggressive risk factor modification therapy.

Context: Individual contributions of obesity and physical fitness (physical activity and functional capacity) to risk of coronary heart disease in women remain unclear., Objective: To investigate the relationships of measures of obesity (body mass index [BMI], waist circumference, waist-hip ratio, and waist-height ratio) and physical fitness (self-reported Duke Activity Status Index [DASI] and Postmenopausal Estrogen-Progestin Intervention questionnaire [PEPI-Q] scores) with coronary artery disease (CAD) risk factors, angiographic CAD, and adverse cardiovascular (CV) events in women evaluated for suspected myocardial ischemia., Design, Setting, and Participants: The National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) is a multicenter prospective cohort study. From 1996-2000, 936 women were enrolled at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (mean follow-up, 3.9 [SD, 1.8] years) for adverse outcomes., Main Outcome Measures: Prevalence of obstructive CAD (any angiographic stenosis >or=50%) and incidence of adverse CV events (all-cause death or hospitalization for nonfatal myocardial infarction, stroke, congestive heart failure, unstable angina, or other vascular events) during follow-up., Results: Of 906 women (mean age, 58 [SD, 12] years) with complete data, 19% were of nonwhite race, 76% were overweight (BMI >or=25), 70% had low functional capacity (DASI scores <25, equivalent to

Background: Obesity and the metabolic syndrome frequently coexist. Both are associated with cardiovascular disease (CVD). However, the contribution of obesity to cardiovascular risk, independent of the presence of the metabolic syndrome, remains controversial., Methods and Results: From the WISE study, 780 women referred for coronary angiography to evaluate suspected myocardial ischemia were classified by body mass index (BMI; <24.9=normal, n=184; > or =25.0 to < or =29.9=overweight, n=269; > or =30.0=obese, n=327) and presence (n=451) or absence (n=329) of the metabolic syndrome, further classified by diabetes status. Prevalence of significant angiographic coronary artery disease (CAD; > or =50% stenosis) and 3-year risk of CVD were compared by BMI and metabolic status. The metabolic syndrome and BMI were strongly associated, but only metabolic syndrome was associated with significant CAD. Similarly, unit increases in BMI (normal to overweight to obese) were not associated with 3-year risk of death (adjusted hazard ratio [HR] 0.92, 95% CI 0.59 to 1.51) or major adverse cardiovascular event (MACE: death, nonfatal myocardial infarction, stroke, congestive heart failure; adjusted HR 0.95, 95% CI 0.71 to 1.27), whereas metabolic status (normal to metabolic syndrome to diabetes) conferred an approximate 2-fold adjusted risk of death (HR 2.01, 95% CI 1.26 to 3.20) and MACE (HR 1.88, 95% CI 1.38 to 2.57). Levels of C-reactive protein (hs-CRP) were more strongly associated with metabolic syndrome than BMI but were not independently associated with 3-year risk of death or MACE., Conclusions: The metabolic syndrome but not BMI predicts future cardiovascular risk in women. Although it remains prudent to recommend weight loss in overweight and obese women, control of all modifiable risk factors in both normal and overweight persons to prevent transition to the metabolic syndrome should be considered the ultimate goal.

Background: Serum amyloid-alpha (SAA) is a sensitive marker of an acute inflammatory state. Like high-sensitivity C-reactive protein (hs-CRP), SAA has been linked to atherosclerosis. However, prior studies have yielded inconsistent results, and the independent predictive value of SAA for coronary artery disease (CAD) severity and cardiovascular events remains unclear., Methods and Results: A total of 705 women referred for coronary angiography for suspected myocardial ischemia underwent plasma assays for SAA and hs-CRP, quantitative angiographic assessment, and follow-up evaluation. Cardiovascular events were death, myocardial infarction, congestive heart failure, stroke, and other vascular events. The women's mean age was 58 years (range 21 to 86 years), and 18% were nonwhite. SAA and hs-CRP were associated with a broad range of CAD risk factors. After adjustment for these risk factors, SAA levels were independently but moderately associated with angiographic CAD (P=0.004 to 0.04) and highly predictive of 3-year cardiovascular events (P<0.0001). By comparison, hs-CRP was not associated with angiographic CAD (P=0.08 to 0.35) but, like SAA, was strongly and independently predictive of adverse cardiovascular outcome (P<0.0001)., Conclusions: Our results show a strong independent relationship between SAA and future cardiovascular events, similar to that found for hs-CRP. Although SAA was independently but moderately associated with angiographic CAD, this association was not found for hs-CRP. These results are consistent with the hypothesis that systemic inflammation, manifested by high SAA or hs-CRP levels, may promote atherosclerotic plaque destabilization, in addition to exerting a possible direct effect on atherogenesis.

Background: The metabolic syndrome, which is characterized by a constellation of fasting hyperglycemia, hypertriglyceridemia, low HDL cholesterol, hypertension, and/or abdominal obesity, is a risk factor for the development of coronary artery disease (CAD) and cardiovascular events. The interrelationship between metabolic status and CAD on cardiovascular risk in women is not known., Methods and Results: We evaluated interrelationships between angiographic CAD, the metabolic syndrome, and incident cardiovascular events among 755 women from the Women's Ischemia Syndrome Evaluation (WISE) study who were referred for coronary angiography to evaluate suspected myocardial ischemia; 25% of the cohort had the metabolic syndrome at study entry. Compared with women with normal metabolic status, women with the metabolic syndrome had a significantly lower 4-year survival rate (94.3% versus 97.8%, P=0.03) and event-free survival from major adverse cardiovascular events (death, nonfatal myocardial infarction, stroke, or congestive heart failure; 87.8% versus 93.5%, P=0.003). When the subjects were stratified by the presence or absence of angiographically significant CAD at study entry, in women with angiographically significant CAD, the metabolic syndrome resulted in significantly higher risk of cardiovascular events than in women with normal metabolic status (hazard ratio 4.93, 95% CI 1.02 to 23.76; P=0.05), whereas it did not result in increased 4-year cardiovascular risk in women without angiographically significant CAD (hazard ratio 1.41, 95% CI 0.32 to 6.32; P=0.65)., Conclusions: These data suggest that in women with suspected myocardial ischemia, the metabolic syndrome modifies the cardiovascular risk associated with angiographic CAD. Specifically, the metabolic syndrome was found to be a predictor of 4-year cardiovascular risk only when associated with significant angiographic CAD.

Background: We previously reported in a cross-sectional analysis an adverse relationship between weight cycling and HDL-cholesterol but not angiographic obstructive coronary artery disease (CAD) among women undergoing coronary angiography for suspected ischemia in the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE). We now examine the relationship between weight cycling and prospective adverse cardiovascular outcome in this group. Methods: 795 women enrolled between 1996–2001 in the WISE undergoing coronary angiography for evaluation of suspected ischemia and followed for a median of 6.0 years (interquartile range = 3.4 years). Adverse outcome was defined as a composite of all-cause death, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure. Weight cycling was defined as the intentional loss of at least 10 lbs. (4.5 kgs.) at least three times during the women’s lifetime. Results: Women (n = 224) who reported a history of weight cycling were younger; more often white and better educated compared those without this history. At baseline, women with a weight cycling history had lower HDL-C values, higher body mass index, larger waist circumferences and higher values for fasting blood sugar, but no difference in obstructive CAD prevalence or severity. There was an inverse relationship between weight cycling and adverse composite cardiovascular outcome, whereby fewer of women with a history of weight cycling experienced an adverse outcome as compared to non-cyclers (21% vs 29%, respectively, p = 0.03). Conclusions: Despite an adverse association with HDL-cholesterol in women undergoing coronary angiography for suspected ischemia, weight cycling was associated with a lower adverse outcome rate in women with suspected ischemia. [ABSTRACT FROM AUTHOR]

Studies have reported an association between obstructive sleep apnea (OSA) and cardiovascular disease (CVD) morbidity and mortality. Proposed mechanisms include endothelial dysfunction and atherosclerosis. We aimed to investigate the associations of OSA with endothelial dysfunction and subclinical atherosclerotic coronary artery disease (CAD), and assess the impact of race on these associations. We used data from the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, a community-based prospective cohort with approximately equal representation of black and white participants. OSA severity was measured in 765 individuals using the apnea-hypopnea index (AHI). Endothelial dysfunction was measured using the Endo-PAT device, expressed as Framingham reactive hyperemia index (F_RHI). Coronary artery calcium (CAC), a marker of subclinical CAD, was quantified by electron beam computed tomography. There were 498 (65%) female participants, 282 (37%) black individuals, and 204 (26%) participants with moderate/severe OSA (AHI ≥15). In univariate models, moderate/severe OSA was associated with lower F_RHI and higher CAC, as well as several traditional CVD risk factors including older age, male sex, hypertension, diabetes, higher body mass index, and lower high-density lipoprotein cholesterol levels. In a multivariable model, individuals with moderate/severe OSA had 10% lower F_RHI and 35% higher CAC, which did not reach statistical significance (p=0.08 for both comparisons). There was no significant interaction of race on the association of OSA with F_RHI or CAC (p-value >0.1 for all comparisons). In a community-based cohort comprised of black and white participants, moderate/severe OSA was modestly associated with endothelial dysfunction and subclinical atherosclerotic CAD. These associations did not vary by race. [ABSTRACT FROM AUTHOR]

Background: Women with signs and symptoms of ischemia, no obstructive coronary artery disease (CAD) and preserved left ventricular ejection fraction (EF) often have diastolic dysfunction and experience elevated rates of major adverse cardiac events (MACE), including heart failure (HF) hospitalization with preserved ejection fraction (HFpEF). We evaluated the predictive value of inflammatory biomarkers for long-term HF hospitalization and all-cause mortality in these women. Methods: We performed a cross-sectional analysis to investigate the relationships between inflammatory biomarkers [serum interleukin-6 (IL-6), C-reactive protein (hs-CRP) and serum amyloid A (SAA)] and median of 6 years follow-up for all-cause mortality and HF hospitalization among women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF. Multivariable Cox regression analysis tested associations between biomarker levels and adverse outcomes. Results: Among 390 women, mean age 56 ± 11 years, median follow up of 6 years, we observed that there is continuous association between IL-6 level and HF hospitalization (adjusted hazard ratio [AHR] 2.5 [1.2–5.0], p = 0.02). In addition, we found significant association between IL-6, SAA levels and all-cause mortality AHR (1.8 [1.1–3.0], p = 0.01) (1.5 [1.0–2.1], p = 0.04), respectively. Conclusion: In women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF, elevated IL-6 predicted HF hospitalization and all-cause mortality, while SAA level was only associated with all-cause mortality. These results suggest that inflammation plays a role in the pathogenesis of development of HFpEF, as well all-cause mortality. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of remote ischemic peri-conditioning (RIPC) during inter-facility air medical transport of ST-segment elevation myocardial infarction (STEMI) patients on the incidence of acute kidney injury (AKI) following primary percutaneous coronary intervention (pPCI).Background: STEMI patients who receive pPCI have an increased risk of AKI for which there is no well-defined prophylactic therapy in the setting of emergent pPCI.Methods: Using the ACTION Registry-GWTG, we evaluated the impact of RIPC applied during inter-facility helicopter transport of STEMI patients from non-PCI capable hospitals to 2 PCI-hospitals in the United States between March, 2013 and September, 2015 on the incidence of AKI following pPCI. AKI was defined as ≥0.3 mg/dL increase in creatinine within 48-72 hours after pPCI.Results: Patients who received RIPC (n = 127), compared to those who did not (n = 92), were less likely to have AKI (11 of 127 patients [8.7%] vs. 17 of 92 patients [18.5%]; adjusted odds ratio = 0.32, 95% CI 0.12-0.85, P = 0.023) and all-cause in-hospital mortality (2 of 127 patients [1.6%] vs. 7 of 92 patients [7.6%]; adjusted odds ratio = 0.14, 95% CI 0.02-0.86, P = 0.034) after adjusting for socio-demographic and clinical characteristics. There was no difference in hospital length of stay (3 days [interquartile range, 2-4] vs. 3 days [interquartile range, 2-5], P = 0.357) between the 2 groups.Conclusion: RIPC applied during inter-facility helicopter transport of STEMI patients for pPCI is associated with lower incidence of AKI and in-hospital mortality. The use of RIPC for renal protection in STEMI patients warrants further in depth investigation. [ABSTRACT FROM AUTHOR]

BACKGROUND Elevated night time/daytime blood pressure (BP) ratios are associated with cardiovascular morbidity and mortality. We evaluated the associations between sleep/awake BP ratios and sleep disturbances. METHODS Sleep disturbances were assessed by in-home actigraphy and diary measures for nine nights, and polysomnography (PSG) for two nights; ambulatory BP was measured for at least 48 h. Participants were 186 middle-aged African-American and Caucasian men and women who were free from prevalent myocardial infarction, stroke, history of interventional cardiology procedures, diabetes, and diagnosed apnea or other sleep disorders. RESULTS Results showed that the greater the sleep/wake ratios of BP, the more fragmented the sleep, the greater the proportion in stage 1 (light) sleep and the smaller the proportion in rapid eye movement (REM) sleep, and the greater the number of arousals from sleep. These results were independent of age, race, gender, Framingham Risk status, cardiovascular medications, body mass index, and apnea/ hypopnea index. Indicators of psychosocial stress were not greater among those with higher sleep/wake BP ratios. CONCLUSIONS Findings are consistent with the hypothesis that elevated night time/ daytime pressure may be a consequence of poor sleep. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate the impact of high-intensity exertion and heat stress on electrocardiographic changes during fire suppression and recovery. Methods: Healthy firefighters completed a live-fire training evolution. Each firefighter was randomly assigned to complete either two or three intervals of fire suppression tasks followed by a structured recovery. Firefighters were continuously monitored using 12-lead Holter electrocardiogram. Results: Most firefighters (71.4%) exceeded their maximum heart rate and one third had pathological ST events. Nearly one third of each of these abnormalities persisted throughout recovery period. Longer fire suppression intervals did not affect the incidence of these abnormalities. Conclusions: Fire suppression is associated with ST-segment changes among firefighters at low risk for cardiovascular disease. These abnormalities continued into initial recovery even though cooling and rehydration were provided. [ABSTRACT FROM AUTHOR]

Abstract: Background: Blood pressure predicts the risk of cardiovascular disease events in a linear, graded manner. Factors associated with significant short-term increases in blood pressure are not well established. We aimed to identify predictors of a significant increase in blood pressure over a 1-year period among nonhypertensive, community-dwelling adults. Methods: From the community-based Heart Strategies Concentrating on Risk Evaluation study, 509 nonhypertensive adults (mean age 58 years; 68% were female; 24% were black) had baseline and 1-year assessments of blood pressure. Demographics, medical history, anthropometrics, lipids/lipoproteins, physical activity, and psychologic status were measured at both intervals. A “significant” increase in blood pressure was defined as an increase in systolic blood pressure of greater than 20 mm Hg, diastolic blood pressure of greater than 10 mm Hg, or initiation of antihypertensive medication. Results: At 1 year, 22% of participants had a significant increase in blood pressure. In multivariable analysis, baseline body mass index (BMI) and a greater than 5% increase in weight or waist circumference were associated with a significant increase in blood pressure (adjusted relative risk 2.09; 95% confidence interval, 1.35-3.21). The adverse effect of an increase in weight and waist circumference on blood pressure was evident in subgroup analyses by age, race, baseline BMI, and regular exercise. Conclusions: Baseline BMI and a greater than 5% increase in weight or waist circumference over 1 year are associated with a significant increase in blood pressure. These data emphasize the need for weight maintenance. They also serve to stratify individuals who may benefit from close clinical observation and preventive intervention. [Copyright &y& Elsevier]