Standard Cardiovascular Disease Risk Factors Research Articles

Abstract 11708: Examining the Impact of Social Determinants of Health in Cardiovascular Disease Risk Factors: Insights From an Implementation Study in a Rural Primary Care Clinic

Introduction: The social determinants of health (SDoH) are associated with uncontrolled cardiovascular disease (CVD) risk factors and warrant attention. Methods: We describe methods and cross-sectional results of the SDoH screening and referral system at a resident-run primary care clinic at Cayuga Medical Center (total 30 residents ~539 patients seen/month with 12% no shows) starting from Nov 2019. Eight domains of SDoH including food security, utility, housing, childcare, finances, transportation, literacy, and social support were selected based on local county data and focus group discussions. We developed an annual screening tool and referral system integrated into the electronic medical record for any SDoH positive patients to the community health and social workers (CHW/SW), who facilitated access to community resources. Patient education about available community resources, regular follow-up visits with the physician and CHW/SW, and periodic SDoH screening were other key components. Results: Among 741 patients (Hypertension and Diabetes), 607 (82%) patients underwent SDoH screening (Table). 200 (33%) patients had at least one domain of SDoH (SDoH +) and received SDoH interventions whereas, 407 (67%) did not have any SDoH. The three most common SDoH were lack of social support (61%), transportation (35%) and finance issues (25%). Patients in the SDoH+ group were younger, with higher percentage of non-White race/ethnicity, unemployment, disability, living alone, current smokers, illicit substance use, anxiety, depression, obesity, and opioid use with statistical significance. However, there were no significant differences in CVD risk factors like SBP (138.3 vs 138.4 mmHg), DBP (84 vs 83 mmHg), HbA1c (6.4 vs 6.2) and LDL-c (103.7 vs 101.5 mg/dL). Conclusions: In addition to controlling standard CVD risk factors, implementation of SDoH routine screening and referral system in a primary care clinic may help in mitigating CVD burden as seen in our study.

Associations between electrocardiogram and carotid ultrasound parameters: a healthy chinese group study.

Background: Electrocardiogram (ECG) and carotid ultrasound (CUS) are important tools for the diagnosis and prediction of cardiovascular disease (CVD). This study aimed to investigate the associations between ECG and CUS parameters and explore the feasibility of assessing carotid health with ECG. Methods: This cross-sectional cohort study enrolled 319 healthy Chinese subjects. Standard 12-lead ECG parameters (including the ST-segment amplitude [STA]), CUS parameters (intima-media thickness [IMT] and blood flow resistance index [RI]), and CVD risk factors (including sex, age, and systolic blood pressure [SBP]) were collected for analysis. Participants were divided into the high-level RI group (average RI ≥ 0.76, n = 171) and the normal RI group (average RI < 0.76, n = 148). Linear and stepwise multivariable regression models were performed to explore the associations between ECG and CUS parameters. Results: Statistically significant differences in sex, age, SBP, STA and other ECG parameters were observed in the normal and the high-level RI group. The STA in lead V3 yielded stronger significant correlations (r = 0.27–0.42, p < 0.001) with RI than STA in other leads, while ECG parameters yielded weak correlations with IMT (|r| ≤ 0.20, p < 0.05). STA in lead V2 or V3, sex, age, and SBP had independent contributions (p < 0.01) to predicting RI in the stepwise multivariable models, although the models for IMT had only CVD risk factors (age, body mass index, and triglyceride) as independent variables. The prediction model for RI in the left proximal common carotid artery (CCA) had higher adjusted R2 (adjusted R2 = 0.31) than the model for RI in the left middle CCA (adjusted R2 = 0.29) and the model for RI in the right proximal CCA (adjusted R2 = 0.20). Conclusion: In a cohort of healthy Chinese individuals, the STA was associated with the RI of CCA, which indicated that ECG could be utilized to assess carotid health. The utilization of ECG might contribute to a rapid screening of carotid health with convenient operations.

Psychosocial Well-Being and Progression of Coronary Artery Calcification in Midlife Women.

BackgroundPrevention of cardiovascular disease (CVD) is a public health priority. The combination of physical activity, a healthy diet, and abstaining from tobacco plays an important role in prevention whereas aspects of psychosocial well‐being have largely been examined separately with conflicting results. This study evaluated whether the combination of indices of psychosocial well‐being was associated with less progression of coronary artery calcium (CAC).Methods and ResultsParticipants were 312 women (mean age 50.8) from the SWAN (Study of Women’s Health Across the Nation) ancillary Heart Study, free of clinical CVD at baseline. A composite psychosocial well‐being score was created from 6 validated psychosocial questionnaires assessing optimism, vitality, life engagement, life satisfaction, rewarding multiple roles, and positive affect. Subclinical CAC progression was defined as an increase of ≥10 Agatston units over 2.3 years measured using electron beam tomography. Relative risk (RR) regression models examined the effect of well‐being on CAC progression, progressively adjusting for sociodemographic factors, depression, healthy lifestyle behaviors, and standard CVD risk factors. At baseline, 42.9% had a CAC score >0, and progression was observed in 17.6%. Well‐being was associated with less progression (RR, 0.909; 95% CI, 0.843−0.979; P=0.012), which remained significant with adjustment for potential confounders, depression, and health behaviors. Further adjustment for standard CVD risk factors weakened the association for the total sample (RR, 0.943; 95% CI, 0.871−1.020; P=0.142) but remained significant for the 134 women with baseline CAC>0 (RR, 0.921; 95% CI, 0.852−0.995; P=0.037).ConclusionsOptimum early prevention of CVD in women may result from including the mind side of the mind‐heart‐body continuum.

Self-compassion and subclinical cardiovascular disease among midlife women.

Self-compassion is a positive psychological construct characterized by extending compassion toward oneself, often during periods of suffering. Whereas self-compassion has been associated with psychological outcomes, research linking self-compassion to physical health is limited. We tested the hypothesis that greater self-compassion would be associated with less subclinical cardiovascular disease (CVD) as assessed by carotid intima-media thickness (IMT). We adjusted for demographics, CVD risk factors and additionally depressive symptoms in these associations. Women (N = 195; M age = 59 years) without CVD were recruited. Women completed questionnaires (Neff Self-Compassion Scale, Center for Epidemiology Studies of Depression Scale); physical measures (body mass index [BMI], blood pressure [BP]); phlebotomy (lipids, insulin resistance); and ultrasound assessments of the carotid artery (mean, maximal IMT). Cross-sectional associations between self-compassion and IMT were assessed in linear regression models covarying for age, race/ethnicity, education, and CVD risk factors (BMI, BP, insulin resistance, lipids, medications), and additionally depressive symptoms. Higher self-compassion was associated with lower mean IMT [B(SE)=-.03 (.01), p = .02], adjusting for demographic factors and CVD risk factors. Associations persisted adjusting for depressive symptoms. When considering self-compassion subscale bifactors, the positive self-compassion bifactor (self-compassion), but not negative self-compassion bifactor (self-coldness), was related to lower IMT. Self-compassion is associated with lower subclinical CVD. Associations were not explained by standard CVD risk factors nor by depressive symptoms. Future research should consider whether enhancing self-compassion improves women's vascular health. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Sleep and cardiovascular outcomes in relation to nocturnal hypertension: the J-HOP Nocturnal Blood Pressure Study.

There is a lack of data on how nighttime blood pressure (BP) might modify the relationship between sleep duration and cardiovascular disease (CVD) risk. Self-reported sleep duration data were available for 2253/2562 patients from the J-HOP Nocturnal BP study; of these, 2236 had complete follow-up data (mean age 63.0 years, 83% using antihypertensive drugs). CVD outcomes included stroke, coronary artery disease (CAD), and atherosclerotic CVD (ASCVD [stroke + CAD]). Associations between sleep duration and nighttime home BP (measured using a validated, automatic, oscillometric device) were determined. During a mean follow-up of 7.1 ± 3.8 years, there were 133 ASCVD events (52 strokes and 81 CAD events). Short sleep duration (<6 versus ≥6 and <9 h/night) was significantly associated with the risk of ASCVD (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.07-3.22), especially stroke (HR 2.47, 95% CI 1.08-5.63). When nighttime systolic BP was <120 mmHg, those with a sleep duration <6 versus ≥6 and <9 h/night had a significantly higher risk of ASCVD and CAD events (HR [95% CI] 3.46 [1.52-7.92] and 3.24 [1.21-8.69], respectively). Even patients with "optimal" sleep duration (≥6 and <9 h/night) were at significantly higher risk of stroke when nighttime systolic BP was uncontrolled (HR [95% CI] 2.76 [1.26-6.04]). Adding sleep duration and nighttime BP to a base model with standard CVD risk factors significantly improved model performance for stroke (C-statistic 0.795, 95% CI 0.737-0.856; p = 0.038). These findings highlight the importance of both optimal sleep duration and control of nocturnal hypertension for reducing the risk of CVD, especially stroke. Clinical Trial registration: URL: http://www.umin.ac.jp/icdr/index.html . Unique identifier: UMIN000000894.

Cardiovascular Risk Factors Are Associated With Future Cancer

BackgroundThe extent to which co-occurrence of cardiovascular disease (CVD) and cancer is due to shared risk factors or other mechanisms is unknown. ObjectivesThis study investigated the association of standard CVD risk factors, CVD biomarkers, pre-existing CVD, and ideal cardiovascular (CV) health metrics with the development of future cancer. MethodsThis study prospectively followed Framingham Heart Study and PREVEND (Prevention of Renal and Vascular End-Stage Disease) study participants free of cancer at baseline and ascertained histology-proven cancer. This study assessed the association of baseline CV risk factors, 10-year atherosclerotic (ASCVD) risk score, established CVD biomarkers, prevalent CVD, and the American Heart Association (AHA) Life’s Simple 7 CV health score with incident cancer using multivariable Cox models. Analyses of interim CVD events with incident cancer used time-dependent covariates. ResultsAmong 20,305 participants (mean age 50 ± 14 years; 54% women), 2,548 incident cancer cases occurred over a median follow-up of 15.0 years (quartile 1 to 3: 13.3 to 15.0 years). Traditional CVD risk factors, including age, sex, and smoking status, were independently associated with cancer (p < 0.001 for all). Estimated 10-year ASCVD risk was also associated with future cancer (hazard ratio [HR]: 1.16 per 5% increase in risk; 95% confidence interval [CI] 1.14 to 1.17; p < 0.001). The study found that natriuretic peptides (tertile 3 vs. tertile 1; HR: 1.40; 95% CI: 1.03 to 1.91; p = 0.035) were associated with incident cancer but not high-sensitivity troponin (p = 0.47). Prevalent CVD and the development of interim CV events were not associated with higher risk of subsequent cancer. However, ideal CV health was associated with lower future cancer risk (HR: 0.95 per 1-point increase in the AHA health score; 95% CI: 0.92 to 0.99; p = 0.009). ConclusionsCVD risk, as captured by traditional CVD risk factors, 10-year ASCVD risk score, and natriuretic peptide concentrations are associated with increased risk of future cancer. Conversely, a heart healthy lifestyle is associated with a lower risk of future cancer. These data suggest that the association between CVD and future cancer is attributable to shared risk factors.

Sexual Assault and Carotid Plaque Among Midlife Women.

BackgroundSexual assault is a risk factor for poor mental health, yet its relationship to cardiovascular disease risk is not understood. We tested whether women with a sexual assault history had greater carotid atherosclerosis levels and progression over midlife.Methods and ResultsA total of 169 non‐smoking, cardiovascular disease‐free women aged 40 to 60 years were assessed twice over 5 years. At each point, women completed questionnaires, physical measures, phlebotomy, and carotid ultrasounds. Associations between sexual assault and carotid plaque level (score 0, 1, ≥2) and progression (score change) were assessed in multinomial logistic and linear regression models, adjusted for age, race/ethnicity, education, body mass index, blood pressure, lipids, insulin resistance, and additionally depression/post‐traumatic stress symptoms; 28% of the women reported a sexual assault history. Relative to non‐exposed women, women with a sexual assault history had an over 4‐fold odds of a plaque score of ≥2 at baseline (≥2, odds ratio [OR] [95% CI]=4.35 [1.48–12.79], P=0.008; 1, OR [95% CI]=0.49 [0.12–1.97], P=0.32, versus no plaque; multivariable); and an over 3‐fold odds of plaque ≥2 at follow‐up (≥2, OR [95% CI]=3.65 [1.40–9.51], P=0.008; 1, OR [95% CI]=1.52 [0.46–4.99], P=0.49, versus no plaque; multivariable). Women with a sexual assault history also had an over 3‐folds greater odds of a plaque score progression of ≥2 (OR [95% CI]=3.48[1.11–10.93], P=0.033, multivariable). Neither depression nor post‐traumatic symptoms were related to plaque.ConclusionsSexual assault is associated with greater carotid atherosclerosis level and progression over midlife. Associations were not explained by standard cardiovascular disease risk factors. Future work should consider whether sexual assault prevention reduces women's cardiovascular disease risk.

Abstract 13902: Gender Differences in Lipoprotein Parameters in Cardiovascular Disease Risk; The Framingham Offspring Study

Introduction: Elevated serum lipoprotein cholesterol levels have been considered as atherosclerosis cardiovascular disease (ASCVD) risk factors. However, gender differences among these lipoproteins have not become clear. Hypothesis: Our hypothesis was that gender differences exist with regard to serum lipoprotein cholesterol levels and the risk of ASCVD risk in the prospective Framingham Offspring Study. Methods: A total of 1300 men and 1676 women, none of whom had ASCVD at baseline, were followed for a median time of 16 years for new onset fatal or non fatal myocardial infarction or stroke, coronary angioplasty or bypass, or carotid or peripheral vascular surgery (302 of 1300 or 23.2% of men and 226 of 1676 or 13.5% of women developed). At baseline, standard risk factors including fasting total and high density lipoprotein (HDL) cholesterol, and triglycerides were assessed, as were direct, small dense, and large low density lipoprotein (LDL) cholesterol and LDL triglyceride (LDL-TG), remnant lipoprotein cholesterol and lipoprotein(a) were measured. Univariate and multivariate analyses were carried out to assess relationships to disease risk. Results: All parameters were associated with ASCVD risk on univariate analysis. On multivariate analysis after controlling for all standard risk factors (age, hypertension, use of anti-hypertensive medication, diabetes, smoking, total cholesterol, HDL cholesterol, and use of cholesterol lowering medication), only lipoprotein(a) was significant in men with a 1.26 hazard ratio (P = 0.009), while small dense LDL cholesterol and LDL-TG, but not lipoprotein(a), were significant risk factors in women (hazard ratios 1.65 and 1.35, P = 0.007 and 0.015, respectively). Using the pooled cohort equation, only lipoprotein(a) added significant risk information in men and only small dense LDL cholesterol and LDL-TG added significant risk information in women. Conclusions: Our data indicate that men are at significantly higher disease risk then women, and that elevated lipoprotein(a) is a significant independent ASCVD risk factor in men, while small dense LDL cholesterol and LDL-TG are significant independent ASCVD risk factors in women after controlling for all other standard cardiovascular disease risk factors.

Association of Lower Plasma Homoarginine Concentrations with Greater Risk of All-Cause Mortality in the Community: The Framingham Offspring Study.

Lower circulating homoarginine concentrations have been associated with morbidity and mortality in patients with established cardiovascular disease (CVD). We assayed plasma homoarginine concentrations in 3331 Framingham Offspring Study participants attending examination cycle six (mean age 58.6 years, 53% women). We evaluated correlates of plasma homoarginine and related homoarginine to incident CVD and death. We also classified participants as having higher (upper quartile) versus lower (lower three quartiles) homoarginine and previously assayed asymmetric dimethylarginine (ADMA) concentrations, and created cross-classification groups. We observed 630 incident CVD events and 940 deaths during a median follow-up of 18 years. In multivariable regression analysis, homoarginine was associated positively with male sex, body mass index, anti-hypertensive medication use and systolic blood pressure, but inversely with age and smoking. Higher homoarginine levels were associated with a lower mortality risk (hazard ratio (HR) per SD increment, 0.83, 95% CI: 0.74–0.93) adjusting for standard CVD risk factors, and ADMA. Among the cross-classification groups, participants with higher homoarginine and lower ADMA had a lower mortality risk (HR, 0.81, 95% CI: 0.67–0.98) compared to those with low levels of both. Further studies are needed to dissect the mechanisms of the association of homoarginine and mortality over decades in the community.

Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression.

Aim: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan.Methods: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression.Results: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C < 100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend = 0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population.Conclusions: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

Physiologically assessed hot flashes and endothelial function among midlife women.

Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations. Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol. In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P < 0.05) indicated that among the younger tertile of women in the sample (age 40-53 years), the presence of hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol. Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

Increased Aortic Diameters on Multidetector Computed Tomographic Scan Are Independent Predictors of Incident Adverse Cardiovascular Events: The Framingham Heart Study.

Adverse aortic remodeling, such as dilation, is associated with multiple cardiovascular disease (CVD) risk factors. We sought to determine whether measures of enlarged aortic diameters improve prediction of incident adverse CVD events above standard CVD risk factors in a community-dwelling cohort. Participants from the Framingham Offspring and Third Generation Cohorts (n=3318; aged 48.9±10.3 years), who underwent noncontrast thoracic and abdominal multidetector computed tomography during 2002 to 2005, had complete risk factor profiles, and were free of clinical CVD, were included in this study. Diameters were measured at 4 anatomically defined locations: the ascending thoracic aorta, descending thoracic aorta, the infrarenal abdominal aorta, and lower abdominal aorta. Adverse events comprised CVD death, myocardial infarction, coronary insufficiency, index admission for heart failure, and stroke. Each aortic segment was dichotomized as enlarged (diameter ≥upper 90th percentile for age, sex, and body surface area) or not enlarged; the hazard of an adverse event for an enlarged segment was determined using multivariable-adjusted Cox proportional hazards models. Over a mean 8.8±2.0 years of follow-up, there were 177 incident adverse CVD events. In models adjusted for traditional CVD risk factors, enlarged infrarenal abdominal aorta (hazard ratio=1.57; 95% confidence interval=1.06 to 2.32) and lower abdominal aorta (hazard ratio=1.53; 95% confidence interval=1.00 to 2.34) were associated with an increased hazard of CVD events. Enlarged ascending thoracic aorta and descending thoracic aorta were not significantly associated with CVD events. Among community-dwelling adults initially free of clinical CVD, enlarged infrarenal abdominal aorta and lower abdominal aorta, on noncontrast multidetector computed tomography scans, are independent predictors of incident adverse CVD events above traditional risk factors alone.

Density of calcium in the ascending thoracic aorta and risk of incident cardiovascular disease events

Background and aimsThe volume and density of coronary artery calcium (CAC) both independently predict cardiovascular disease (CVD) beyond standard risk factors, with CAC density inversely associated with incident CVD after accounting for CAC volume. We tested the hypothesis that ascending thoracic aorta calcium (ATAC) volume and density predict incident CVD events independently of CAC. MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of participants without clinical CVD at baseline. ATAC and CAC were measured from baseline cardiac computed tomography (CT). Cox regression models were used to estimate the associations of ATAC volume and density with incident coronary heart disease (CHD) events and CVD events, after adjustment for standard CVD risk factors and CAC volume and density. ResultsAmong 6811 participants, 234 (3.4%) had prevalent ATAC and 3395 (49.8%) had prevalent CAC. Over 10.3 years, 355 CHD and 562 CVD events occurred. One-standard deviation higher ATAC density was associated with a lower risk of CHD (HR 0.48 [95% CI 0.29–0.79], p<0.01) and CVD (HR 0.56 [0.37–0.84], p<0.01) after full adjustment. ATAC volume was not associated with outcomes after full adjustment. ConclusionsATAC was uncommon in a cohort free of clinical CVD at baseline. However, ATAC density was inversely associated with incident CHD and CVD after adjustment for CVD risk factors and CAC volume and density.

Physiologically assessed hot flashes and endothelial function among midlife women.

Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations. Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol. In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P < 0.05) indicated that among the younger tertile of women in the sample (age 40-53 years), the presence of hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol. Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

Aortic-Brachial Arterial Stiffness Gradient and Cardiovascular Risk in the Community: The Framingham Heart Study.

A recent study reported that the aortic-brachial arterial stiffness gradient, defined as carotid-radial/carotid-femoral pulse wave velocity (PWV ratio), predicts all-cause mortality better than carotid-femoral pulse wave velocity (CFPWV) alone in dialysis patients. However, the prognostic significance of PWV ratio for cardiovascular disease (CVD) in the community remains unclear. Accordingly, we assessed the correlates and prognostic value of the PWV ratio in 2114 Framingham Heart Study participants (60±10 years; 56% women) free of overt CVD. Mean PWV ratio decreased from 1.36±0.19 in participants aged <40 years to 0.73±0.21 in those aged ≥80 years. In multivariable linear regression, older age, male sex, higher body mass index, diabetes mellitus, lower high-density lipoprotein cholesterol, higher mean arterial pressure, and higher heart rate were associated with lower PWV ratio (P<0.001 for all). During a median follow-up of 12.6 years, 248 first CVD events occurred. In Cox regression models adjusted for standard CVD risk factors, 1-SD changes in CFPWV (hazard ratio, 1.33; 95% confidence interval, 1.10-1.61) and PWV ratio (hazard ratio, 1.32; 95% confidence interval, 1.09-1.59) were associated with similar CVD risks. Models that included conventional CVD risk factors plus CFPWV or PWV ratio gave the same C statistics (C=0.783). Although PWV ratio has been reported to provide incremental predictive value over CFPWV in dialysis patients, we could not replicate these findings in our community-based sample. Our findings suggest that the prognostic significance of PWV ratio may vary based on baseline CVD risk, and CFPWV should remain the criterion standard for assessing vascular stiffness in the community.

Child Abuse and Neglect and Subclinical Cardiovascular Disease Among Midlife Women.

A childhood history of abuse or neglect may be associated with elevated adult cardiovascular disease (CVD) risk. No studies have examined associations between child abuse/neglect and subclinical CVD using a validated measure of abuse and neglect. We hypothesized that midlife women with a history of childhood abuse or neglect would have increased subclinical CVD beyond standard CVD risk factors. We tested moderation of associations by sleep, hot flashes, and race/ethnicity. Two hundred ninety-five midlife women completed the Child Trauma Questionnaire, physiologic hot flash and actigraphic sleep monitoring, blood draw, and carotid ultrasound (intima media thickness [IMT]; plaque). Relations between abuse/neglect and outcomes were tested in linear regression models adjusting for demographic, psychosocial, and CVD risk factors. Interactions with sleep, hot flashes, and race/ethnicity were tested. Forty-five percent of women reported a history of child abuse or neglect. Women with any child abuse or neglect had higher IMT [b(SE) = .039 (.011), p = .001] and carotid plaque [odds ratio (95% [CI] = 1.95 [1.15-3.33]); p = .014] than nonabused/neglected women. Furthermore, physical abuse, emotional abuse, and emotional neglect were associated with higher subclinical CVD. Sexual abuse was associated with higher IMT among nonwhite women. Interactions with sleep time and sleep hot flashes (p values < .05) indicated that higher subclinical CVD with an abuse/neglect history was observed primarily among women sleeping less than 6 hours/night or with sleep hot flashes. A history of child abuse or neglect is associated with higher subclinical CVD in women, particularly when paired with short sleep or hot flashes. Findings underscore the importance of childhood adversity in midlife women's CVD risk.

Relations of Arterial Stiffness With Postural Change in Mean Arterial Pressure in Middle-Aged Adults: The Framingham Heart Study.

Impaired regulation of blood pressure on standing can lead to adverse outcomes, including falls, syncope, and disorientation. Mean arterial pressure (MAP) typically increases on standing; however, an insufficient increase or a decline in MAP on standing may result in decreased cerebral perfusion. Orthostatic hypotension has been reported in older people with increased arterial stiffness, whereas the association between orthostatic change in MAP and arterial stiffness in young- to middle-aged individuals has not been examined. We analyzed orthostatic blood pressure response and comprehensive hemodynamic data in 3205 participants (1693 [53%] women) in the Framingham Heart Study Third Generation cohort. Participants were predominantly middle aged (mean age: 46±9 years). Arterial stiffness was assessed using carotid-femoral pulse wave velocity, forward pressure wave amplitude, and characteristic impedance of the aorta. Adjusting for standard cardiovascular disease risk factors, orthostatic change in MAP (6.9±7.7 mm Hg) was inversely associated with carotid-femoral pulse wave velocity (partial correlation, rp=-0.084; P<0.0001), forward wave amplitude (rp=-0.129; P<0.0001), and characteristic impedance (rp=-0.094; P<0.0001). The negative relation between forward wave amplitude and change in MAP on standing was accentuated in women (P=0.002 for sex interaction). Thus, higher aortic stiffness was associated with a blunted orthostatic increase in MAP, even in middle age. The clinical implications of these findings warrant further study.

Abstract P032: Increased Abdominal Aortic Diameters on Multidetector CT Scan Are Independent Predictors of Incident Adverse Cardiovascular Events: The Framingham Heart Study

Introduction: Adverse aortic remodeling, such as dilation, is cross-sectionally associated with multiple cardiovascular disease (CVD) risk factors. We sought to determine whether increased, though not necessarily aneurysmal, abdominal aortic diameters augment prediction of incident adverse CVD events above standard CVD risk factors in a community-dwelling cohort. This may be useful since the aorta is often incidentally visualized on computed tomography (CT) body scans performed for indications other than CVD risk stratification. Methods: Participants (N=3318, aged 50±10y, 51% M) from the Framingham Offspring and Third Generation Cohorts who were free of clinical CVD, had complete risk factor profiles (collected at the adjacent cycle exams), and had non-contrast, abdominal multidetector CT scans (MDCT) during 2002-2005 were included in this study. Anteroposterior (AP) and left-right (LR) diameters were measured in the infrarenal (IAA) and lower abdominal (LAA) aorta. The IAA was measured at 5 cm above the aortoiliac bifurcation and the LAA was measured at one slice level (2.5mm) above the bifurcation of the abdominal aorta into the common iliac arteries. For each segment, the greater of AP and LR diameters was used in the analyses. Adverse events comprised CVD death, myocardial infarction, coronary insufficiency, index admission for heart failure, and stroke. For each aortic segment, hazard of an adverse event for enlarged IAA or LAA diameter (enlarged was defined as ≥ upper 90 th percentile diameter for age, sex and BSA) was determined using multivariable (MV) adjusted Cox proportional hazards models. Results: Over a mean 8.8±2.0y of follow-up, there were 149 incident adverse CVD events. In multivariable models adjusted for traditional CVD risk factors, enlarged IAA was associated with greater hazard of an adverse CVD event (HR 1.62; 95% CI 1.07-2.46; p=0.022). However, the association of enlarged LAA with adverse CVD events was borderline (HR 1.56; 95% CI 0.99-2.46; p=0.054). Conclusion: Among community-dwelling adults initially free of clinical CVD, enlarged infrarenal abdominal (IAA) aortic diameter, as determined from noncontrast MDCT scans, augments prediction of incident adverse CVD events above traditional risk factors alone.

Relation of Risk Factors and Abdominal Aortic Calcium to Progression of Coronary Artery Calcium (from the Framingham Heart Study)

Coronary artery calcium (CAC) and abdominal aortic calcium (AAC) on multidetector computed tomography (MDCT) permit assessment of the presence and burden of coronary and systemic atherosclerosis. Risk factors for progression of CAC and AAC and the association of AAC with CAC progression have not been well characterized in a community-dwelling cohort. We studied 1,959 asymptomatic participants from the Framingham Heart Study who underwent serial MDCT scans with a median interval of 6.1years. Primary outcomes were (a) the incidence of CAC and AAC (CAC >0 and AAC >0 with baseline CAC= 0 and AAC= 0) and (b) absolute progression of CAC (CAC > baseline CAC and AAC > baseline AAC). Covariates were collected at adjacent cycle examinations and included age, gender, use of antihypertensive therapy, use of lipid-lowering therapy, cigarette smoking, and total and high-density lipoprotein cholesterol. Predictors for CAC and AAC progression included baseline CAC, baseline AAC, lipid-lowering therapy, diabetes, high-density lipoprotein cholesterol, BMI, and serum creatinine. Multivariable stepwise logistic and linear regression models were used to test the association of these risk factors with CAC and AAC. Those who developed incident CAC on follow-up scanning comprised 18.8% of 1,124 participants, and 84.9% of 780 participants, with detectable baseline CAC, had further progression. Baseline AAC was a predictor of both CAC incidence and progression, independent of other risk factors. In stepwise models, addition of baseline AAC slightly improved the area under the curve from 0.72 (0.68 to 0.76) to 0.74 (0.70 to 0.78). In conclusion, standard cardiovascular disease risk factors are associated with incidence and progression of CAC and AAC, and AAC augments CAC incidence and progression above cardiovascular disease risk factors.

Cardiovascular disease prevalence and insulin resistance in the Kyushu–Okinawa Population Study and the Framingham Offspring Study

Age-adjusted cardiovascular disease (CVD) prevalence rates are significantly lower in Japan than in the United States. Our aim was to compare CVD risk in participants in Fukuoka and Framingham. We measured glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C, and triglycerides in men and women from Fukuoka (n=1108), and age (median, 53years) and gender-matched subjects from Framingham (n=1101). Blood pressure, body mass index, use of medications, and history of CVD were also assessed. CVD prevalence rates were more than 6-fold higher in Framingham men and women than their Fukuoka counterparts (P<.001). Median body mass index, LDL-C, insulin levels, and insulin resistance assessment in Fukuoka men and women were significantly (P<.01) lower than in Framingham; however, diabetes prevalence in Fukuoka men was significantly (P<.01) higher than in Framingham men, whereas female rates were similar, as were levels of systolic blood pressure. High-density lipoprotein cholesterol and surprisingly small dense LDL-C levels were significantly (P<.001) higher in Fukuoka than in Framingham. Standard risk factors do not account for the large differences in CVD prevalence rates between the 2 populations, and population differences in insulin resistance may explain some of these differences. Our data are consistent with the concept that the CVD prevalence rate in a Japanese population is much lower than those observed in the United States, and that these differences cannot be explained by standard CVD risk factors, but may relate to marked population differences in insulin resistance.