Measures Of Subclinical Cardiovascular Disease Research Articles

Associations of Ambulatory Blood Pressure Measurements With High-Sensitivity Troponin and Natriuretic Peptide Levels in SPRINT.

Nighttime blood pressure (BP) has greater prognostic importance for cardiovascular disease (CVD) than daytime BP, but less is known about nighttime and daytime BP associations with measures of subclinical CVD. Among 897 Systolic Blood Pressure Intervention Trial Study (SPRINT) participants with 24-hour ambulatory BP monitoring obtained near the 27-month study visit, 849 (95%) had N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) measured at the 24-month study visit. Multivariable linear regression analyses were performed to evaluate the associations of nighttime and daytime BP with cardiac biomarker levels. The mean age was 69 ± 12 years, 28% were African American, and mean nighttime and daytime SBP were 121 ± 16 mm Hg and 132 ± 14 mm Hg, respectively. In multivariable models, compared with the lowest tertile of nighttime systolic BP, the highest tertile was associated with 48% higher NT-proBNP levels (adjusted geometric mean ratio [GMR] = 1.48, 95% CI: 1.22, 1.79), and 19% higher hs-cTnT levels (adjusted GMR = 1.19, 95% CI: 1.07, 1.32). In contrast, the highest vs. lowest tertile of daytime systolic BP was not associated with NT-proBNP (adjusted GMR = 1.09, 95% CI: 0.88, 1.34), but was associated with 16% higher hs-cTnT levels (adjusted GMR = 1.16, 95% CI: 1.04, 1.30). Similar results were observed using diastolic BP. In SPRINT, both higher nighttime and daytime BP were independently associated with higher hs-cTnT levels, but only higher nighttime BP was associated with higher NT-proBNP levels.

Subclinical vascular composites predict clinical cardiovascular disease, stroke, and dementia: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aimsSubclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores. MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) followed 6814 participants (45–84 years of age) from baseline in 2000–2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supineblood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound. Baseline subclinical CVD measures were transformed into z-scores before factor analysis to derive composite factor scores. Time to clinical event for all-cause CVD, CHD, stroke and ICD code-based dementia events were modeled using Cox proportional hazards models reported as area under the curve (AUC) with 95% Confidence Intervals (95%CI) at 10 and 15 years of follow-up. All models included all factor scores together, and adjustment for conventional risk scores for global CVD, stroke, and dementia. ResultsAfter factor selection, 24 subclinical measures aggregated into four distinct factors representing: blood pressure, atherosclerosis, arteriosclerosis, and cardiac factors. Each factor significantly predicted time to CVD events and dementia at 10 and 15 years independent of each other and conventional risk scores. Subclinical vascular composites of atherosclerosis and arteriosclerosis best predicted time to clinical events of CVD, CHD, stroke, and dementia. These results were consistent across sex and racial and ethnic groups. ConclusionsSubclinical vascular composites of atherosclerosis and arteriosclerosis may be useful biomarkers to inform the vascular pathways contributing to events of CVD, CHD, stroke, and dementia.

1233-P: The Association between Subgingival Microbiome, Subclinical Cardiovascular Disease, and Type 1 Diabetes

Background: Dysbiosis in the subgingival microbiome is the root cause of periodontal disease, a risk factor of cardiovascular disease (CVD), but its association with subclinical CVD, particularly among those with type 1 diabetes (T1D) is unclear. Methods: We included 283 subjects with (n=141) and without (n=142) T1D. We performed 16S rDNA sequencing on subgingival plaque samples and identified amplicon sequence variants. Subclinical CVD was measured by carotid intima-media thickness (cIMT), pulse wave velocity (PWV), and brachial artery distensibility (BrachD). Results: Beta diversity differed between T1D and the nondiabetes (ND) group (F = 1.66, P=0.024). As shown in Figure 1, in the stratified generalized linear model (adjusted for age, gender, race, smoking, alcohol drinking, BMI, and additionally HbA1c in the T1D model), we observed 4 taxa in the T1D group and 28 taxa in the ND group to be associated with cIMT (all Padj< 0.05). Moreover, 8 and 17 taxa were associated with BrachD (lower value suggests worse status) in T1D and ND groups, and 6 and 5 for PWV (all Padj < 0.05). Some associations were in opposite directions by diabetes status, especially for cIMT. Conclusion: We observed differences in the subgingival microbiome profile between those with and without T1D. Subgingival microbiome taxa were associated with subclinical CVD measures, with some differences observed by diabetes status. Disclosure M. Xiao: None. A. Sarkar: None. J.K. Snell-Bergeon: None. S. Chandrasekaran: None. L.R. Johnson: None. B.R. Burkhardt: None. J. Petrosino: None. A.C. Alman: None. Funding National Institutes of Health (5R01DE026480)

Abstract P392: Association Between Blood Pressure Variability and Subclinical Measures of Cardiovascular Disease in Desk Workers

Introduction: Previous research has demonstrated that variability in resting blood pressure (BP) across arms, measurements, or days may be associated with an increased risk for cardiovascular disease (CVD) and mortality. Yet, the extent to which BP variability increases cardiovascular risk and the mechanisms explaining this association are unclear. This study evaluated associations between BP variability with subclinical pathways of CVD development (arterial stiffness (pulse wave velocity [PWV]) and cardiac autonomic function (heart rate variability [HRV]) in desk workers. Hypothesis: Higher BP variability will be associated with higher PWV and lower (worse) HRV Methods: This secondary analysis of baseline data from the Effect of Reducing Sedentary on Blood Pressure randomized controlled trial included 265 sedentary and inactive desk workers (mean age 44.9±11.6 years; 82.0% white; 57.9% female) with elevated-to-stage 2 hypertension and who were not using antihypertensive medication. Sequential BP measurements determined the arm with the higher systolic BP by using an oscillometric device (Omron HEM-907XL). BP was then measured at least twice from the arm with the higher systolic BP at the first (visit-1) and second (visit-2) visits, occurring ≤30 days apart. Systolic BP variability metrics included inter-arm (first measurements between arms at visit-1), intra-arm (first two measurements on the arm with higher systolic BP at visit-1), and inter-visit (average BP from repeated measurements on the same arm across visits-1 and -2). Subclinical measures of CVD included resting carotid- femoral(cfPWV) and carotid-radial(crPWV) PWV (Complier Analyse) and the log transformed standard deviation of normal R-R intervals (SDNN) and the root mean square of the successive differences (RMSSD) HRV measures (Polar Electro). Adjusted linear regression estimated the associations between subclinical measures of CVD and BP variability metrics; Metrics were operationalized into three categories: differences of 0-5 mmHg, 6-10 mmHg, and 11 or more mmHg. Results: The prevalence of having 6 mmHg or more difference for the inter-arm, intra-arm, and inter-visit systolic BP was 43%, 38%, and 53%, respectively. PWV and HRV were not different across categories of inter-arm systolic BP variability or inter-visit systolic BP variability (all p>0.05). However, a same-day intra-arm difference in systolic BP of 6-10 mmHg within visit-1 was associated with higher cfPWV (β=0.42 m/s, (95% CI: 0.07, 0.77) as compared to those with an intra-arm difference of 0-5 mmHg. Conclusion: These data suggest that higher systolic BP variability in the same arm within visit, but not variability across arms or between visits, may be associated with higher aortic stiffness in desk workers with untreated elevated-to-stage 2 hypertension.

The association between leptin and subclinical cardiovascular disease explained by body fat: Observational and Mendelian randomization analyses

Background and aimsLeptin has been associated with adverse effects on cardiovascular disease, but the effect of confounding by body fat in these associations remains unclear. To investigate associations between leptin and heart function and subclinical cardiovascular disease adjusted for total body fat, and to investigate the causal relation between leptin and cardiovascular disease using Mendelian randomisation. Methods and resultsLeptin concentrations, total body fat and diverse measures of subclinical cardiovascular disease were determined in participants of the Netherlands Epidemiology of Obesity study. Linear regression between leptin concentration and measures of heart function, ECG measures, and carotid intima media thickness as a measure of subclinical atherosclerosis was adjusted for potential confounding factors, and additionally including total body fat. We analysed the combined effects of genetic variants from a GWAS on leptin concentrations in publicly-available summary statistics of coronary heart disease GWAS (CARDIoGRAMplusC4D, n = 184,305). As many as 6107 men and women, mean (SD) age 56 (6) years, BMI 26 (4) kg/m2, and median leptin concentration 12.1 μg (IQR: 6.7–22.6) were included.In observational analyses, leptin was weakly associated with heart function and subclinical cardiovascular disease, but these associations attenuated when adjusting for total body fat. A doubling of genetically-determined leptin concentration was associated with an odds ratio of cardiovascular disease of 0.69 (0.37, 1.27). ConclusionObservational associations between leptin and subclinical measures of cardiovascular disease were largely explained by differences in total body fat. Results of analyses of genetically-determined leptin and coronary heart disease risk were inconclusive due to a large confidence interval.

NEIGHBORHOOD QUALITY AS IT RELATES TO HEALTH AND WELL-BEING IN OLDER AFRICAN AMERICANS

Abstract With the burgeoning older adult population, there will be an increased demand for neighborhood environments that are conducive to successful aging. For example, the need for affordable and usable housing developments for older adults that provide greater opportunities for social engagement, social services, and convenience to neighborhood resources (e.g., grocery stores, healthcare) will continue to rise. Several initiatives have sought to develop age-friendly neighborhoods, which focused on improving accessibility and affordability of community resources. However, limited effort has focused on the health and cognitive effects of neighborhood-level socioeconomic disadvantage, with respect to neighborhood income, education, employment, and housing quality. This symposium will include presentations from two studies that explored how neighborhood disadvantage (measured by the Area Deprivation Index) relates to health and cognition. The objectives of the proposed symposium are the following: (1) discuss how neighborhood disadvantage relates to subjective and objective measures of physical health; and (2) discuss how neighborhood disadvantage relates to cognitive functioning. Allan and colleagues explored the association between neighborhood disadvantage as it relates to changes in self-reported health and objective measures (i.e., blood pressure) of health among older Black adults. Wright and colleagues explored the association between neighborhood disadvantage and measures of subclinical cardiovascular disease in older Black and White adults. Aiken-Morgan and colleagues examined associations between neighborhood disadvantage and cognitive functioning among Black older adults. Lastly, McCain and colleagues explored associations between neighborhood disadvantage and mobility among Black older adults.

Abstract 12239: Objectively Measured Physical Activity Decreases the Risk of Subclinical Cardiovascular Disease: A Systematic Review

Introduction: Physical activity (PA) decreases the risk of cardiovascular events, but to what degree this is related to effects on surrogate markers of subclinical cardiovascular disease (CVD) is unclear. Clarifying the relationship between objectively measured PA and subclinical CVD would provide justification for using measures of subclinical CVD in clinical trials of PA interventions. Hypothesis: We hypothesized that higher levels of objectively measured PA are associated with less subclinical CVD. Methods: We performed a systematic review using Medline, Embase, CINAHL and Cochrane (January 1, 2000 - January 12, 2022). Studies of adult populations that examined the relationship between objectively measured PA (accelerometry) and subclinical CVD were included. Markers for subclinical CVD included: ankle brachial index ( n =4 studies); arterial stiffness ( n =31); carotid artery plaque/stenosis and intima media thickness ( n =9); coronary artery atherosclerosis ( n =4); endothelial function ( n =8); measures of cardiac structure and function ( n =4); and eight studies included multiple of the aforementioned outcomes. For those studies, we considered results on each outcome separately. Risk of bias was also assessed. Results: PA was inversely associated with subclinical CVD in 60 of 78 included analyses (76.9%). Of these, five studies (6.4%) found only an association with higher levels of PA. In six studies (7.7%), PA was no longer associated with subclinical CVD after adjustment for confounders. Seven analyses (9.0%) demonstrated mixed results but demonstrated an inverse relationship between PA and subclinical CVD in specific circumstances. Only 18 studies (23.1%) suggested that PA was not associated with decreased subclinical CVD. Conclusions: Increased PA is associated with less subclinical CVD across diverse populations. Interventions to increase PA have the potential to reduce the burden of subclinical CVD and, therefore, clinical CVD events.

Abstract 9978: Non-Traditional Risk Markers for Incident Coronary Artery Calcium Among Persons ≥65 Years Old: The Multi-Ethnic Study of Atherosclerosis

Introduction: Initiation of coronary artery calcium (CAC) is an important milestone associated with a marked increase in cardiovascular disease (CVD) risk. However, traditional risk factors do not perform well for CVD risk stratification among older persons. Hypothesis: Contrasting to measures of subclinical CVD, blood-based non-traditional risk factors will not strongly predict incident CAC in older adults. Methods: There were 815 participants > 65 years old with CAC=0 at Visit 1. We calculated multivariable Cox hazards ratios and C-statistics for the association of non-traditional risk factors with incident CAC. Results: The mean age was 70.2 years old, 67% were women, and 35% were Black. A total of 55% developed incident CAC with a median follow-up time to incident CAC of 3.6 years. The largest proportion of persons with incident CAC was among those with microalbuminuria (Figure). Albuminuria (aHR=1.54, 95% CI: 1.10-2.16) and thoracic calcification (TAC) (aHR=1.38, 95% CI: 1.10-1.75) were significantly associated with incident CAC, while 1-SD higher level of apolipoprotein-B, lipoprotein(a), high-sensitivity troponin T, N-terminal pro-brain natriuretic peptide and C-reactive protein were not. When added to demographic information, albuminuria and TAC provided a greater C-statistic improvement (+0.044, p=0.01) versus all traditional risk factors combined (+0.029, p=0.09). Conclusions: Among non-traditional risk factors and measures of subclinical CVD, only albuminuria and TAC were significantly associated with incident CAC in persons >65 years old. Identification of older persons with albuminuria or TAC may help guide the utility and timing of repeat CAC scoring in older persons with baseline CAC=0.

Circulating anti-Müllerian hormone levels and markers of subclinical cardiovascular disease in middle-aged and older men

ContextRecent research suggests that higher circulating anti-Müllerian hormone (AMH) levels are associated with less frequent occurrence of (subclinical) cardiovascular disease (CVD) in women, but evidence in men is limited. ObjectiveWe investigated whether circulating AMH levels are associated with measures of subclinical CVD in middle-aged and older men. DesignProspective cohort study with a median follow-up time of 8.7 years. Serum AMH was measured at baseline. We assessed both cross-sectional and longitudinal associations using linear regression models adjusted for confounders. SettingDutch middle-aged and older men from the community. Participants394 men (aged 40–80 years) with an available AMH measurement at baseline. Main outcome measuresAt baseline (2001−2002): carotid intima-media thickness (CIMT), pulse wave velocity (PWV), abdominal aortic diameter, and Framingham risk score (FRS) predictions. At follow-up (2010−2011): CIMT, mean carotid aortic plaque score, PWV, and FRS predictions. All outcomes were transformed using rank-based inverse normal transformation to meet the normality assumption. ResultsHigher AMH levels were associated with lower CIMT at baseline (β = −0.04; 95%CI = 0.07, −0.01), but not with the other measures of subclinical CVD at baseline. Longitudinal analyses suggested that higher baseline AMH levels were associated with lower mean plaque scores at follow-up (β = −0.03, 95%CI = −0.07, 0.00), but not with the other follow-up outcomes. ConclusionsOur results suggest that AMH is associated with current CIMT and future carotid aortic plaque burden in men, implying that circulating AMH levels are potentially associated with local atherosclerosis rather than with total aortic stiffness.

Young men of color lower on adult attachment anxiety have higher carotid-intima media thickness compared to white young men: The exploration of an unexpected finding

Cardiovascular disease (CVD) remains the number one cause of death among men in the United States. Emerging research demonstrates that socioemotional mechanisms such as adult attachment, or the ways in which individuals are able to form and maintain socioemotional bonds, may impact physical health via alterations in physiological stress functioning. However, there may be key differences in the relation between attachment and physical health by race and sexual orientation. Thus, this study sought to examine the potential moderating effect of race and sexual orientation on the association between adult attachment and carotid-intima media thickness (cIMT), a measure of subclinical cardiovascular disease, among young men. The sample consisted of 72 young men (mean [SD] age = 22.92 [3.23]: 30.6 % identified as White, 30.6 % as Black, and 38.8 % as Other), each of which were surveyed and underwent an ultrasound to measure cIMT. Ordinary Least Squares (OLS) regression was used in order to examine our study hypotheses. We first ran a main effects model to examine adult attachment’s (i.e., anxiety and avoidance) association with mean cIMT. We then ran two interaction models with an interaction between race/ethnicity and adult-related attachment and sexual orientation and adult attachment. We found that race significantly moderated the association between attachment-related anxiety and mean cIMT in our study sample. However, we did not find evidence to suggest that race moderated the association between attachment-related avoidance and mean cIMT in our study sample. In comparison to White individuals, Black individuals and those who identified as “Other” race with lower scores on attachment-related anxiety had higher mean cIMT. Additionally, higher scores on attachment-related anxiety were associated with lower mean cIMT among Black and “Other” respondents, but not among White respondents. We did not find evidence to suggest that sexual orientation moderated the association between adult attachment and mean cIMT in our study sample. Our findings suggest that adult attachment anxiety may be protective for young men of color but not for White young men. Future research should utilize longitudinal study designs in order to better understand how adult attachment influences CVD risk among racially/ethnically diverse young men.

Abstract 040: Sleep Regularity And Subclinical Markers Of Cardiovascular Disease: The Multi Ethnic Study Of Atherosclerosis (MESA)

Background: Sleep irregularity has been linked to incident cardiovascular disease (CVD). Less is known about sleep regularity and associations with atherosclerosis. Our objective was to examine associations of sleep regularity with measures of atherosclerosis in the diverse MESA cohort. Methods: Participants from the MESA Sleep Study (2010-2013; N=2,032, Mean age: 68.6 ± 9.2 years; 53% Female, 38% White, 28% Black or African American, 23% Hispanic, 11% Chinese) completed 7-days of actigraphy. At the same exam, coronary artery calcium (CAC) was derived from computed tomography, carotid plaque presence and carotid intima-media thickness (cIMT) were derived from ultrasonography, and the ankle brachial index (ABI) was calculated from extremity measured systolic blood pressure. Sleep regularity was quantified by standard deviations in sleep durations and sleep onset time across wear days and categorized in 30 minute (mins) increments. Adjusted relative risk regression models were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CI) for associations of measures of sleep regularity with each subclinical marker of CVD. Models adjusted for demographics, CVD risk factors, and objectively-assessed obstructive sleep apnea. Results: After multivariable adjustment, and compared to those with regular sleep durations (SD≤60 mins), participants with greater sleep duration irregularity (SD>120 mins) were more likely to have high CAC burden [CAC >300; PR (95% CI): 1.36 (1.03-1.78)], carotid plaque [1.10 (1.00-1.22)] and an abnormal ABI [ABI <0.9; 1.74 (1.00-3.02)]. Compared to participants with regular sleep timing (SD≤30 mins), those with irregular sleep timing (SD>90 mins) were 1.38 (1.04-1.83) times more likely to have high CAC burden. Associations did not vary by age or sex. Conclusion: Sleep regularity, particularly sleep duration regularity, was associated with measures of subclinical CVD in this diverse cohort. Sleep regularity is a modifiable sleep dimension worthy of further investigation.

Abstract P162: Cardiovascular Disease And Periodontal Disease In Type 1 Diabetes

Type 1 diabetes (T1D) is a condition in which the body’s immune system destroys insulin-producing beta cells, resulting in hyperglycemia. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in those with T1D. Periodontal disease (PD) is the 6th major complication of T1D. Oral bacteria have been detected in atherosclerotic plaques. Thus, oral bacteria may play a causal role in cardiovascular disease. The aims of this study are to determine how subclinical measures of cardiovascular disease differ by diabetes status and how they are related to the extent of periodontal disease. It is hypothesized that people with T1D will have stiffer vessels with higher pulse wave velocity (PWV), lower brachial artery distensibility (BrachD), and higher carotid intima-media thickness (cIMT) compared to non-diabetic controls. It is also hypothesized that people with T1D will have a higher prevalence of PD compared to non-diabetic controls. Study visits were performed to assess cardiovascular and periodontal outcomes in people with T1D (n=144) and non-diabetic controls (n=147). Univariate analysis was performed using t-test and chi-square to test for significant differences in vascular measures and periodontal status between T1D and controls. Age and sex-adjusted multivariate linear and logistic regression was used to further examine differences in vascular measures and periodontal disease by diabetes status. PWV was significantly higher in people with T1D compared to controls (8.390 +/- 0.111 vs. 7.822 +/- 0.108, p=0.0003). BrachD was significantly lower in people with T1D compared to controls (5.795 +/- 0.095 vs. 6.413 +/- 0.094, p<0.0001). cIMT was significantly higher in people with T1D compared to controls (0.679 +/- 0.009 vs. 0.626 +/- 0.009, p<0.0001). Adults with T1D were significantly more likely to have moderate to severe PD compared to controls (OR = 2.759, 95% CI [1.310-5.811], p=0.0076). Adults with T1D have worse cardiovascular health as measured by stiffer central vessels, more subclinical atherosclerosis, and lower peripheral vessel distensibility. Adults with T1D had almost 3-fold higher risk of moderate to severe PD compared to non-diabetic adults. The relationship between PD and the increased CVD risk in people with T1D warrants further examination.

Association Between Myocardial Strain and Frailty in CHS.

Myocardial strain, measured by speckle-tracking echocardiography, is a novel measure of subclinical cardiovascular disease and may reflect myocardial aging. We evaluated the association between myocardial strain and frailty-a clinical syndrome of lack of physiological reserve. Frailty was defined in participants of the CHS (Cardiovascular Health Study) as having ≥3 of the following clinical criteria: weakness, slowness, weight loss, exhaustion, and inactivity. Using speckle-tracking echocardiography data, we examined the cross-sectional (n=3206) and longitudinal (n=1431) associations with frailty among participants who had at least 1 measure of myocardial strain, left ventricular longitudinal strain (LVLS), left ventricular early diastolic strain rate and left atrial reservoir strain, and no history of cardiovascular disease or heart failure at the time of echocardiography. In cross-sectional analyses, lower (worse) LVLS was associated with prevalent frailty; this association was robust to adjustment for left ventricular ejection fraction (adjusted odds ratio, 1.32 [95% CI, 1.07-1.61] per 1-SD lower strain; P=0.007) and left ventricular stroke volume (adjusted OR, 1.32 [95% CI, 1.08-1.61] per 1-SD lower strain; P=0.007). In longitudinal analyses, adjusted associations of LVLS and left ventricular early diastolic strain with incident frailty were 1.35 ([95% CI, 0.96-1.89] P=0.086) and 1.58 ([95% CI, 1.11-2.27] P=0.013, respectively). Participants who were frail and had the worst LVLS had a 2.2-fold increased risk of death (hazard ratio, 2.20 [95% CI, 1.81-2.66]; P<0.0001). In community-dwelling older adults without prevalent cardiovascular disease, worse LVLS by speckle-tracking echocardiography, reflective of subclinical myocardial dysfunction, was associated with frailty. Frailty and LVLS have an additive effect on mortality risk.

Soluble CD14 Levels in the Jackson Heart Study: Associations With Cardiovascular Disease Risk and Genetic Variants.

[Figure: see text].

The Association Between Myocardial Strain and Frailty in the Cardiovascular Health Study

Myocardial strain, measured by speckle tracking echocardiography (STE), is a novel measure of subclinical cardiovascular disease and may reflect myocardial aging. We aimed to explore the association between myocardial strain and frailty, a clinical syndrome of impaired resilience and lack of physiologic reserve. Frailty was defined in 4,042 participants of the Cardiovascular Health Study (CHS) as having 3 or more of the following clinical criteria: weakness, slowness, shrinking, exhaustion, and inactivity. We examined the cross-sectional and longitudinal associations of left ventricular (LV) longitudinal strain, LV early diastolic strain rate and left atrial reservoir strain with frailty in participants with no history of cardiovascular disease or heart failure at the time of echocardiography. In cross-sectional analyses, LV longitudinal strain, LV early diastolic strain, left atrial reservoir strain and LV ejection fraction (measured by conventional echocardiography) levels were lower (worse) among frail participants than among those who were not frail and pre-frail (p<0.01). This association of LV longitudinal strain and frailty was robust to adjustment by LV ejection fraction (adjusted OR: 1.34, 95% CI: 1.20, 2.09). Conversely, LV ejection fraction was not associated with frailty after adjustment for LV longitudinal strain. In longitudinal analyses, LV longitudinal strain and LV early diastolic strain were associated with incident frailty (adjusted OR: 1.49, 95% CI: 1.07, 2.08) and 1.65, 95% CI: 1.15, 2.25, respectively). In community-dwelling older adults without prevalent cardiovascular disease, worse LV longitudinal strain, reflective of subclinical myocardial dysfunction, was associated with frailty independent of LV ejection fraction and other risk factors.

APOL1 Risk Variants and Subclinical Cardiovascular Disease in Incident Hemodialysis Patients

IntroductionTo better understand the impact of APOL1 risk variants in end-stage renal disease (ESRD) we evaluated associations of APOL1 risk variants with subclinical cardiovascular disease (CVD) and mortality among African Americans initiating hemodialysis and enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in ESRD cohort study. MethodsWe modeled associations of APOL1 risk status (high = 2; low = 0/1 risk alleles) with baseline subclinical CVD (left ventricular [LV] hypertrophy; LV mass; ejection fraction; coronary artery calcification [CAC]; pulse wave velocity [PWV]) using logistic and linear regression and all-cause or cardiovascular mortality using Cox models, adjusting for age, sex, and ancestry. In sensitivity analyses, we further adjusted for systolic blood pressure and Charlson Comorbidity Index. ResultsOf 267 African American participants successfully genotyped for APOL1, 27% were high-risk carriers, 41% were women, and mean age was 53 years. At baseline, APOL1 high- versus low-risk status was independently associated with 50% and 53% lower odds of LV hypertrophy and CAC, respectively, and 10.7% lower LV mass. These associations were robust to further adjustment for comorbidities but not systolic blood pressure. APOL1 risk status was not associated with all-cause or cardiovascular mortality (mean follow-up 2.5 years). ConclusionAmong African American patients with incident hemodialysis, APOL1 high-risk status was associated with better subclinical measures of CVD but not mortality.

Association between marijuana use and electrocardiographic abnormalities by middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

To evaluate the prevalence of electrocardiogram (ECG) abnormalities in marijuana users as an indirect measure of subclinical cardiovascular disease (CVD). Longitudinal and cross-sectional secondary data analysis from the CARDIA (Coronary Artery Risk Development in Young Adults) study. Four communities in the United States. A total of 2585 participants from the 5115 black and white men and women recruited at age 18-30years in 1985 to 1986 in CARDIA. ECG abnormalities coded as minor and major abnormalities with the Minnesota code of electrocardiographic findings at year20. Self-reported current (past 30days) and computed cumulative life-time marijuana use (one 'marijuana-year' corresponds to 365days of use) through assessments every 2-5years. We fitted logistic regression models adjusting for sex, race, center, education, age, tobacco smoking, physical activity, alcohol use and body mass index. Among the 2585 participants with an ECG at year 20, mean age was 46, 57% were women, 45% were black; 83% had past exposure to marijuana and 11% were using marijuana currently. One hundred and seventy-three participants (7%) had major abnormalities and 944 (37%) had minor abnormalities. Comparing current with never use in multivariable-adjusted models, the odds ratio (OR) for major ECG abnormalities was 0.60 [95% confidence interval (CI)=0.32-1.15] and for minor ECG abnormalities 1.21 (95% CI=0.87-1.68). Results did not change after stratifying by sex and race. Cumulative marijuana use was not associated with ECG abnormalities. In a middle-aged US population, life-time cumulative and occasional current marijuana use were not associated with increases in electrocardiogram abnormalities. This adds to the growing body of evidence that occasional marijuana use and cardiovascular disease events and markers of subclinical atherosclerosis are not associated.

Abstract P133: Circulating Anti-Müllerian Hormone and Subclinical Cardiovascular Disease in Middle-aged and Older Men

Introduction: Anti-Müllerian hormone (AMH) is primarily known for its role in sexual differentiation during embryogenesis, and ovarian follicle development in premenopausal women. Furthermore, recent research suggests that higher AMH levels are associated with a lower occurrence of (subclinical) cardiovascular disease (CVD) in both women and men. However, these studies only included a small variety of subclinical CVD measures. We aimed to investigate whether circulating AMH is associated with a wider range of subclinical CVD measures in middle-aged and older men. Hypothesis: Higher AMH levels are associated with more favorable levels of subclinical CVD measures. Methods: We analyzed data from 371 male participants (aged 40-80 years at recruitment) from a Dutch population-based study. AMH was measured in serum samples obtained at recruitment using the Elecsys ® AMH assay (Roche Diagnostics). At baseline we measured carotid intima-media thickness (cIMT)(μm), pulse wave velocity (PWV)(m/s) and aorta diameter (cm), and calculated Framingham risk score predictions. We investigated associations between AMH (μg/L) levels, both continuously and in tertiles, and these outcomes using linear regression models adjusted for known CVD risk factors, free testosterone, free estradiol and dihydroepiandrosterone sulphate (DHEAS). Sensitivity analyses comprised exclusion of prevalent diabetes and CVD cases. Results: Higher AMH levels were associated with a lower cIMT at baseline (β continuousAMH = -6.3, 95%CI: -10.7, -1.9; β T2vsT1 = -30.6, 95%CI: -60.2, -0.9; β T3vsT1 = -39.8, 95%CI: -70.1, -9.6). We observed no statistically significant associations between AMH and the remaining outcomes, but effect estimates indicated that higher AMH levels may be associated with lower PWV (β continuousAMH = -0.02, 95%CI: -0.10, 0.05), and lower Framingham risk score predictions (β continuousAMH = -0.004, 95%CI: -0.008, 0.000). Exclusion of prevalent diabetes and CVD cases did not change our conclusions. Conclusions: The results of this study suggest that higher AMH levels are associated with a lower cIMT in middle-aged and older men. Based on our results we cannot exclude a possible relation between circulating AMH levels and other measures of subclinical cardiovascular disease.

Abstract P135: Aortic Areas at Multiple Locations are Independent Correlates of Multiple Subclinical Cardiovascular Disease Measures

To handle the force from high blood pressure, arteries throughout the vasculature undergo outward remodeling, which can be assessed through measurement of arterial dimension. While the proximal aortic size is indicative of aneurysm risk, other regions of the aorta, such as the descending or abdominal aorta, may be more reflective of general aortic remodeling. However, there have been no studies using multiple measures of aortic size and their association with established subclinical cardiovascular disease (CVD) markers. Therefore, we aimed to measure aortic area at three locations along its length: the ascending thoracic aorta (ASC), the descending thoracic aorta (DSC), and the abdominal aorta (ABD) and to test for associations with subclinical CVD measured via carotid ultrasound, arterial calcification, and brachial ankle pulse-wave velocity (PWV). Preliminary analyses were conducted on data from 279 African ancestry men from Tobago (mean age 64 years, range 53-89 years). Aortic areas (cm 2 ) were measured from computed tomography (CT) scans of the chest (ASC and DSC; measured on the same transverse plane at the location of the pulmonary artery) and the abdomen (ABD; measured at the midpoint of L3). The mean of 3 contiguous CT slices was used for each aortic area measure. Each area was individually tested for association with age, body size, blood pressures, and lifestyle factors (including smoking, physical activity, and alcohol), and significant covariates were included in the fully adjusted models. All aortic areas were correlated with each other (r=0.40-0.66, all P&lt;0.0001). Greater age and weight were predictive of greater aortic area at all three locations (P&lt;0.0001 for all). ASC and DSC were also associated with higher blood pressures (P&lt;0.01, for all). No aortic measure was significantly associated with lifestyle factors. After full adjustment, ASC, DSC, and ABD areas were associated with carotid interadventitial diameter (r=0.34, 0.22, 0.20, respectively; all P&lt;0.001). ASC was also positively associated with carotid intima-media thickness (P&lt;0.01). While ABD was associated with abdominal aortic calcification (P&lt;0.001), no area was associated with coronary artery calcification. Lastly, both ABD and DSC were correlated with greater PWV (r=0.24 and 0.16, P&lt;0.005 for both), with DSC being significantly associated with PWV independent of ABD. This is the first study to test the association of aortic size measured at multiple points with established measures of subclinical CVD. While ASC and DSC were associated with age, blood pressures, and carotid outward remodeling, ABD was more strongly correlated with aging-related vascular changes. Additionally, DSC, which can be measured from clinical chest CTs, may be a novel indicator of arterial stiffness independent of age and blood pressures. Longitudinal studies are needed to determine the predictive value of aortic area measurement.

Social Role-Related Stress and Social Role-Related Reward as Related to Subsequent Subclinical Cardiovascular Disease in a Longitudinal Study of Midlife Women: The Study of Women's Health Across the Nation.

The purpose of this study was to determine if midlife social role quality, defined by the stress and rewards associated with four social roles, is related to later-life subclinical cardiovascular disease (SCVD) in a cohort of women transitioning through menopause. The Study of Women's Health Across the Nation (SWAN) is a longitudinal cohort study of midlife women. Stress and reward from four social roles (spouse, parent, employee, caregiver) were assessed at seven early visits. Later-life SCVD was assessed via carotid ultrasound and brachial-ankle pulse wave velocity at two later visits. We tested whether ever reporting an "extremely" or "quite a bit" stressful role was related to SCVD. We also tested whether cumulative stress and reward, as well as baseline and change in stress and reward were related to SCVD, adjusting for demographics and cardiovascular risk factors. Among 1602 women, reporting a stressful role during midlife (between ages 47 and 52 years) was associated with later-life (age 61 years) carotid intima-media thickness, which was 21 μm thicker than never reporting a stressful role. No significant relationships between stressful roles and other SCVD measures were identified. Cumulative and baseline change models of stress and reward were not related to SCVD. A stressful social role in midlife was associated with greater atherosclerotic burden in later-life in a cohort of women transitioning through menopause. Social role rewards were unrelated to better later-life SCVD. These findings extend the knowledge of stress and cardiovascular disease in women by using measures of stress and reward for multiple social roles over the years of midlife.