Associations Between Flavonoid Intake and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Flavonoids may play a role in mitigating atherosclerotic cardiovascular diseases, with evidence suggesting effects may differ between vascular beds. Studies examining associations with subclinical markers of atherosclerosis between subpopulations with different underlying risks of atherosclerosis are lacking. METHODS: Among 5599 participants from the MESA (Multi-Ethnic Study of Atherosclerosis), associations between dietary flavonoid intakes (estimated from a food frequency questionnaire) and subclinical measures of atherosclerosis (ankle-brachial index, carotid plaques and intima-media thickness, and coronary artery calcification) were examined using repeated measures models. Exposures and outcomes were measured at exam 1 (2000-2002) and exam 5 (2010-2011). Stratified analyses and interaction terms were used to explore effect modification by time, sex, race/ethnicity, and smoking status. RESULTS: In the analytic population, at baseline, ≈46% were men with a median age of 62 (interquartile range, 53-70) years and total flavonoid intakes of 182 (interquartile range, 98-308) mg/d. After multivariable adjustments, participants with the highest (quartile 4) versus lowest (quartile 1) total flavonoid intakes had 26% lower odds of having an ankle-brachial index <1 (odds ratio, 0.74 [95% CI, 0.60-0.92]) and 18% lower odds of having a carotid plaque (odds ratio, 0.82 [95% CI, 0.69-0.99]), averaged over exams 1 and 5. Moderate (quartile 3) to high (quartile 4) intakes of flavonols, flavanol monomers, and anthocyanins were associated with 19% to 34% lower odds of having an ankle-brachial index <1 and 18% to 20% lower odds of having carotid plaque. Participants with the highest intakes of anthocyanins (quartile 4) at baseline had a marginally slower rate of carotid plaque progression than those with moderate intakes (quartiles 2 and 3). There were no significant associations with intima-media thickness or coronary artery calcification. Observed associations did not differ by sex, race/ethnicity, or smoking status. CONCLUSIONS: In this multi-ethnic population, higher dietary flavonoid intakes were associated with lower odds of peripheral and carotid artery atherosclerosis. Increasing intakes of healthy, flavonoid-rich foods may protect against atherosclerosis in the peripheral and carotid arteries.

The ankle-brachial index, gastrocnemius mitochondrial respirometry, and walking performance in people with and without peripheral artery disease.

Background: Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle-brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. Objective: To describe associations of the ABI with mitochondrial respiratory function in gastrocnemius muscle biopsies and associations of gastrocnemius mitochondrial respirometry with 6-minute walk distance in people with and without PAD. Methods: People with (ABI ⩽ 0.90) and without (ABI 1.00-1.40) PAD were enrolled. ABI and 6-minute walk distance were measured. Mitochondrial function of permeabilized myofibers from gastrocnemius biopsies was measured with high-resolution respirometry. Results: A total of 30 people with PAD (71.7 years, mean ABI: 0.64) and 68 without PAD (71.8 years, ABI: 1.17) participated. In non-PAD participants, higher ABI values were associated significantly with better mitochondrial respiration (Pearson correlation for maximal oxidative phosphorylation PCI+II: +0.29, p = 0.016). In PAD, the ABI correlated negatively and not significantly with mitochondrial respiration (Pearson correlation for PCI+II: -0.17, p = 0.38). In people without PAD, better mitochondrial respiration was associated with better 6-minute walk distance (Pearson correlation: +0.51, p < 0.001), but this association was not present in PAD (Pearson correlation: +0.10, p = 0.59). Conclusions: Major differences exist between people with and without PAD in the association of gastrocnemius mitochondrial respiration with ABI and 6-minute walk distance. Among people without PAD, ABI and walking performance were positively associated with mitochondrial respiratory function. These associations were not observed in PAD.

Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial.

People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. -10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed.

Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019.

Importance: Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. Objective: To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. Design, Setting, and Participants: An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. Exposures: In this study, no particular exposure was specifically targeted. Main Outcomes and Measures: The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. Results: In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). Conclusions and Relevance: In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Association between Statin use and Incident Peripheral Artery Disease According to Race, Age, and Presence of Depression in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Peripheral artery disease (PAD) is associated with high morbidity and mortality and has been commonly described as a coronary heart disease equivalent. Statin medications are recommended for primary prevention of atherosclerotic cardiovascular disease (CVD) among other indications. Therefore, understanding the longitudinal relationship of incident PAD is necessary to inform future research on how to prevent the disease. Depression complicates CVD patients' ability to properly adhere to their medications, yet the effect of depression on the relationship between statin use and incident PAD is understudied. People with PAD have a higher incidence of depressive symptoms than people without PAD. Black American and Hispanic populations are disproportionately affected by both PAD and depression yet research on the modifying effect of either race or depression on the relationship between statin use and onset of PAD is minimal. While statin utilization is highest for ages 75-84 years, there is minimal evidence of favorable risk-benefit balance. Consequently, in this project, we examined the relationship between statin use and incident PAD and whether this relationship is modified by race/ethnicity, depressive symptoms, or age. METHODS: We used data on participants from the Multi-Ethnic Study of Atherosclerosis from visit 1 (2000) through study visit 6 (2020) who had three separate measurements of the ankle-brachial index (ABI) taken at visit 1, visit 3, and visit 5. Incident PAD was defined as 1) incident lower extremity amputation or revascularization or 2) ABI less than 0.90 coupled with ABI decrease greater than 0.15 over the follow-up period. Statin use was noted on the study visit prior to incident PAD diagnosis while depressive symptoms were measured at exam 1, visit 3, and visit 5. Propensity score matching was implemented to create balance between the participants in the two treatment groups, that is, statin-treated and statin-untreated groups, to reduce the problem of confounding by indication. Propensity scores were calculated using multivariate logistic regression model to estimate the probability of receiving statin treatment. We used Cox proportional hazards regression to investigate the relationship between time-dependent statin use as well as other risk factors with incident PAD, overall and stratified by 1) race, 2) depression status, and 3) age. RESULTS: A total of 4,210 participants were included in the final matched analytic cohort. There were 810 incident cases (19.3%) of PAD that occurred over an average (mean) of 11.3 years (SD = 5.7) of follow-up time. In the statin-treated group, and with an average follow-up time of 12.5 years (SD = 5.6), there were 281 cases (13.4%) of incident PAD with the average follow-up time of 10.1 years (SD = 5.5), whereas in the statin-untreated group, there were 531 cases (25.2%) (P < 0.001). Results demonstrate a lower risk of PAD event in the statin-treated group compared to the untreated group (hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.33-0.62) over the span of 18.5 years. The interactions between 1) depression and 2) race with statin use for incident PAD were not significant. However, other risk factors which were significant included Black American race that had approximately 30% lower hazard of PAD compared to non-Hispanic White (HR = 0.70, 95% CI: 0.58-0.84); age-stratified models were also fitted, and stain use was still a significant treatment factor for ages 45-54 (HR = 0.45, 95% CI: 0.33-0.63), 55-64 (HR = 0.61, 95% CI: 0.46-0.79), and 65-74 years (HR = 0.61, 95% CI: 0.48-0.78) but not for ages 75-84 years. CONCLUSIONS: Statin use was associated with a decreased risk of incident PAD for those under the age of 75 years. Neither race nor depression significantly modified the relationship between statin use and incident PAD; however, the risk of incident PAD was lower among Black Americans. These findings highlight that the benefit of statin may wane for those over the age of 75 years. Findings also suggest that statin use may not be compromised in those living with depression.

Aspirin and Cardiovascular Risk in Individuals With Elevated Lipoprotein(a): The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Effective therapies for reducing cardiovascular disease (CVD) risk in people with elevated lipoprotein(a) are lacking, especially for primary prevention. Because of the potential association of lipoprotein(a) with thrombosis, we evaluated the relationship between aspirin use and CVD events in people with elevated lipoprotein(a). METHODS AND RESULTS: We used data from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of baseline cardiovascular disease. Due to potential confounding by indication, we matched aspirin users to nonusers using a propensity score based on CVD risk factors. We then evaluated the association between aspirin use and coronary heart disease (CHD) events (CHD death, nonfatal myocardial infarction) stratified by baseline lipoprotein(a) level (threshold of 50 mg/dL) using Cox proportional hazards models with adjustment for CVD risk factors. After propensity matching, the study cohort included 2183 participants, including 1234 (57%) with baseline aspirin use and 423 (19%) with lipoprotein(a) >50 mg/dL. Participants with lipoprotein(a) >50 mg/dL had a higher burden of CVD risk factors, more frequent aspirin use (61.7% versus 55.3%, P=0.02), and higher rate of incident CHD events (13.7% versus 8.9%, P<0.01). Aspirin was associated with a significant reduction in CHD events among those with elevated lipoprotein(a) (hazard ratio, 0.54 [95% CI, 0.32-0.94]; P=0.03). Those with lipoprotein(a) >50 mg/dL and aspirin use had similar CHD risk as those with lipoprotein(a) ≤50 mg/dL regardless of aspirin use. CONCLUSIONS: Aspirin use was associated with a significantly lower risk for CHD events in participants with lipoprotein(a) >50 mg/dL without baseline CVD. The results of this observational propensity-matched study require confirmation in studies with randomization of aspirin use.

Discordance of patient-reported outcome measures with objectively assessed walking decline in peripheral artery disease.

OBJECTIVE: Among people with peripheral artery disease (PAD), perceived change in walking difficulty over time, compared with people without PAD, is unclear. Among people reporting no change in walking difficulty over time, differences in objectively measured change in walking performance between people with and without PAD are unknown. METHODS: A total of 1289 participants were included. Eight hundred seventy-four participants with PAD (aged 71.1 ± 9.1 years) were identified from noninvasive vascular laboratories and 415 without PAD (aged 69.9 ± 7.6 years) were identified from people with normal vascular laboratory testing or general medical practices in Chicago. The Walking Impairment Questionnaire and 6-minute walk were completed at baseline and 1-year follow-up. The Walking Impairment Questionnaire assessed perceived difficulty walking due to symptoms in the calves or buttocks on a Likert scale (range, 0-4). Symptom change was determined by comparing difficulty reported at 1-year follow-up to difficulty reported at baseline. RESULTS: At 1-year follow-up, 31.9% of participants with and 20.6% of participants without PAD reported walking difficulty that was improved (P < .01), whereas 41.2% vs 55%, respectively, reported walking difficulty that was unchanged (P < .01). Among all reporting no change in walking difficulty, participants with PAD declined in 6-minute walk, whereas participants without PAD improved (-10 vs +15 meters; mean difference, -25; 95% confidence interval, -38 to -13; P < .01). CONCLUSIONS: Most people with PAD reported improvement or no change in walking difficulty from calf or buttock symptoms at one-year follow-up. Among all participants who perceived stable walking ability, those with PAD had significant greater declines in objectively measured walking performance, compared with people without PAD.

Disparities in Diagnosis, Treatment, and Outcomes of Peripheral Artery Disease: JACC Scientific Statement.

Disparities by sex, race, socioeconomic status, and geography exist in diagnosis, treatment, and outcomes for people with lower extremity peripheral artery disease (PAD). PAD prevalence is similar in men and women, but women have more atypical symptoms and undergo lower extremity revascularization at older ages compared to men. People who are Black have an approximately 2-fold higher prevalence of PAD, compared to people who are White and have more atypical symptoms, greater mobility loss, less optimal medical care, and higher amputation rates. Although fewer data are available for other races, people with PAD who are Hispanic have higher amputation rates than White people. Rates of amputation also vary by geography in the United States, with the highest rates of amputation in the southeastern United States. To improve PAD outcomes, intentional actions to eliminate disparities are necessary, including clinician education, patient education with culturally appropriate messaging, improved access to high-quality health care, science focused on disparity elimination, and health policy changes.

Nutritional Avocado Intervention Improves Physical Activity Measures in Hispanic/Latino Families: A Cluster RCT.

Introduction: Nutrition and physical activity are key components for the prevention of cardiovascular disease. There remains a paucity of trial data on the effect of specific nutritional interventions on physical activity and sedentary time. One question is how a common nutrient-dense food such as avocado may impact physical activity and sedentary time in Hispanic/Latino families, a group that reports the lowest levels of physical activity. Design: This is a 6-month clustered RCT. Setting/participants: Seventy-two families (235 individuals) who identified as Hispanic/Latino were enrolled through the San Ysidro Health Center (San Diego, CA) between April 2017 and June 2018. Intervention: After a 2-week run-in period, 35 families were randomized to the intervention arm (14 avocados/family/week), and 37 families were assigned to the control arm (3 avocados/family/week). Main outcome measures: Linear mixed-effects models were used to assess changes in physical activity (MET minutes per week) between the groups during the 6-month trial. Secondary outcomes included sedentary time (minutes/week), BMI, and systolic and diastolic blood pressures. Results: An adherence goal of >80% was achieved for both arms. Total mean physical activity increased by 2,197 MET minutes per week more in the intervention group (p<0.01) than in the control group, driven by between-group differences in moderate (p<0.01) versus vigorous (p=0.06) physical activity. After accounting for longitudinal repeated measures per participant and nested family effects, total adult physical activity remained significantly higher in the intervention than in the control group (+1,163 MET minutes per week on average per participant), with a significant intervention interaction term (p<0.01). There were no significant changes in sedentary time, BMI, or blood pressure. Conclusions: Higher allocation of avocados was associated with significantly higher physical activity and no adverse changes in BMI or blood pressure, suggesting that this nutritional intervention may have beneficial pleiotropic effects.Trial registration: This study is registered at www.clinicaltrials.gov as NCT02903433.

Serum reactivity to citrullinated protein/peptide antigens and left ventricular structure and function in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Antibodies to citrullinated protein antigens have been linked to altered left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA). Serum reactivity to several citrullinated protein/peptide antigens has been identified in RA, which are detectable years before RA onset and in individuals who may never develop RA. Among community-living individuals without heart failure (HF) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated associations between serum reactivity to citrullinated protein/peptide antigens, LV mass, LV ejection fraction (LVEF), and incident HF. METHODS: Among 1232 MESA participants, we measured serum reactivity to 28 different citrullinated proteins/peptides using a multiplex bead-based array. Each antibody was defined as having extremely high reactivity (EHR) if >95th percentile cut-off in MESA. Number of EHR antibody responses to citrullinated protein/peptide antigens were summed for each participant (range 0-28). LV mass(g) and LVEF(%) were measured on cardiac MRI. Associations between EHR antibodies and LV mass and LVEF were evaluated using linear regression. Cox proportional hazards models were used to evaluate associations between EHR antibodies and incident HF during 11 years of follow-up, adjusting for age, gender, race/ethnicity, smoking status, systolic blood pressure, use of anti-hypertensive medications, self-reported arthritis, IL-6, body surface area, and estimated glomerular filtration rate. RESULTS: Mean age was 65±10, 50% were female, 40% were White, 21% were Black, 26% were Hispanic/Latino, and 14% were Chinese. Twenty-seven percent of MESA participants had extremely high reactivity to ≥ 1 citrullinated protein/peptide antigen. In fully adjusted analysis, every additional EHR antibody was significantly associated with 0.1% lower LVEF (95% CI: -0.17%, -0.02%). No association was observed with LV mass (ß per additional EHR antibody) = 0.13±0.15 (p = 0.37)). Neither the presence nor number of EHR antibodies was associated with incident HF during follow-up (HR per additional EHR antibody = 1.008 (95% CI: 0.97, 1.05)). CONCLUSION: Greater number of extremely highly reactive antibodies was associated with lower LVEF, but not with LV mass or incident HF. Thus, serum reactivity to citrullinated protein/peptide antigens was associated with subtle subclinical changes in myocardial contractility, but the significance in relation to clinically apparent HF is uncertain.

Home-Based Walking Exercise and Supervised Treadmill Exercise in Patients With Peripheral Artery Disease: An Individual Participant Data Meta-Analysis.

Importance: Few people with lower extremity peripheral artery disease (PAD) participate in supervised treadmill exercise covered by the Center for Medicare and Medicaid Services. In people with PAD, the benefits of home-based walking exercise, relative to supervised exercise, remain unclear. Objective: To study whether home-based walking exercise improves 6-minute walk (6MW) more than supervised treadmill exercise in people with PAD (defined as Ankle Brachial Index ≤0.90). Data Sources: Data were combined from 5 randomized clinical trials of exercise therapy for PAD using individual participant data meta-analyses, published from 2009 to 2022. Study Selection: Of the 5 clinical trials, 3 clinical trials compared supervised treadmill exercise to nonexercise control (N = 370) and 2 clinical trials compared an effective home-based walking exercise intervention to nonexercise control (N = 349). Data Extraction and Synthesis: Individual participant-level data from 5 randomized clinical trials led by 1 investigative team were combined. The 5 randomized clinical trials included 3 clinical trials of supervised treadmill exercise and 2 effective home-based walking exercise interventions. Main Outcomes and Measures: Change in 6MW distance, maximum treadmill walking distance, and Walking Impairment Questionnaire at 6-month follow-up. The supervised treadmill exercise intervention consisted of treadmill exercise in the presence of an exercise physiologist, conducted 3 days weekly for up to 50 minutes per session. Home-based walking exercise consisted of a behavioral intervention in which a coach helped participants walk for exercise in or around home for up to 5 days per week for 50 minutes per session. Results: A total of 719 participants with PAD (mean [SD] age, 68.8 [9.5] years; 46.5% female) were included (349 in a home-based exercise clinical trial and 370 in a supervised exercise trial). Compared with nonexercise control, supervised treadmill exercise was associated with significantly improved 6MW by 32.9 m (95% CI, 20.6-45.6; P < .001) and home-based walking exercise was associated with significantly improved 6MW by 50.7 m (95% CI, 34.8-66.7; P < .001). Compared with supervised treadmill exercise, home-based walking exercise was associated with significantly greater improvement in 6MW distance (between-group difference: 23.8 m [95% CI, 3.6, 44.0; P = .02]) but significantly less improvement in maximum treadmill walking distance (between-group difference:-132.5 m [95% CI, -192.9 to -72.1; P < .001]). Conclusions and Relevance: In this individual participant data meta-analyses, compared with supervised exercise, home-based walking exercise was associated with greater improvement in 6MW in people with PAD. These findings support home-based walking exercise as a first-line therapy for walking limitations in PAD.

Lipoprotein(a) and the pooled cohort equations for ASCVD risk prediction: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) but is not included in the Pooled Cohort Equations (PCE). We aimed to assess how well the PCE predict 10-year event rates in individuals with elevated Lp(a), and whether the addition of Lp(a) improves risk prediction. METHODS: We compared observed versus PCE-predicted 10-year ASCVD event rates, stratified by Lp(a) level and ASCVD risk category using Poisson regression, and evaluated the association between Lp(a) > 50 mg/dL and ASCVD risk using Cox proportional hazards models in the Multi-Ethnic Study of Atherosclerosis (MESA). We evaluated the C-index and net reclassification improvement (NRI) with addition of Lp(a) to the PCE. RESULTS: The study population included 6639 individuals (20%, n = 1325 with elevated Lp(a)). The PCE accurately predicted 10-year event rates for individuals with elevated Lp(a) with observed event rates falling within predicted limits. Elevated Lp(a) was associated with increased risk of CVD events overall (HR 1.27, 95% CI 1.00-1.60), particularly in low (HR 2.45, 95% CI 1.40-4.31), and high-risk (HR 1.41, 95% CI 1.02-1.96) individuals. Continuous NRI (95% CI) with the addition of Lp(a) to the PCE for CVD was 0.0963 (0.0158-0.1953) overall, and 0.2999 (0.0876, 0.5525) among low-risk individuals. CONCLUSIONS: The PCE performs well for event rate prediction in individuals with elevated Lp(a). However, Lp(a) is associated with increased CVD risk, and the addition of Lp(a) to the PCE improves risk prediction, particularly among low-risk individuals. These results lend support for increasing use of Lp(a) testing for risk assessment.

Lipoprotein(a) and coronary artery calcium in comparison with other lipid biomarkers: The multi-ethnic study of atherosclerosis.

BACKGROUND: Coronary artery calcium (CAC) scoring is often used for atherosclerotic cardiovascular disease (ASCVD) risk stratification in individuals with elevated lipoprotein(a) [Lp(a)]. OBJECTIVE: To evaluate associations between Lp(a) and baseline CAC (volume/density) and CAC progression compared to other lipid biomarkers. METHODS: We utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of individuals without clinical ASCVD, excluding statin users. We evaluated the associations between Lp(a), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, total cholesterol, apolipoprotein B, and non-HDL-C with baseline CAC and annual CAC progression using multivariable ordinal regression with adjustment for ASCVD risk factors. Analyses were also stratified by median age. RESULTS: In 5,597 participants (2,726 at median 9.5-year follow-up), Lp(a) was not associated with baseline CAC volume or density and was modestly associated with volume progression (OR 1.11, 95% CI 1.03-1.21). However, other biomarkers were positively associated with baseline volume and volume progression (LDL-C: OR 1.26, 95% CI: 1.19-1.33 and OR 1.22, 95% CI: 1.15-1.30, respectively), except HDL-C which was inversely associated. LDL-C, total cholesterol and non-HDL-C were inversely associated with baseline density. In participants <62 years of age, Lp(a) was modestly associated with baseline CAC volume (OR 1.10, 95% CI: 1.00-1.20) and volume progression (OR 1.16 95% CI: 1.04-1.30). CONCLUSIONS: In contrast to other lipid biomarkers, Lp(a) was not associated with baseline CAC volume or density and was only modestly associated with volume progression. Our findings suggest that Lp(a) is not as robustly associated with CAC as other lipid biomarkers.

Coronary Artery Calcium Density and Cardiovascular Events by Volume Level: The MESA.

BACKGROUND: The Agatston coronary artery calcium (CAC) score provides robust cardiovascular disease risk prediction but upweights plaque area by a density factor. Density, however, has been shown to be inversely associated with events. Using CAC volume and density separately improves risk prediction, but it is unclear how to apply this method clinically. We aimed to evaluate the association between CAC density and cardiovascular disease across the spectrum of CAC volume to better understand how to incorporate these metrics into a single score. METHODS: We performed an analysis of MESA (Multi-Ethnic Study of Atherosclerosis) participants with detectable CAC to evaluate the association between CAC density and events by level of CAC volume using multivariable Cox regression models. RESULTS: In a cohort of 3316 participants, there was a significant interaction (P<0.001) between CAC volume and density for coronary heart disease (CHD) risk (myocardial infarction, CHD death, resuscitated cardiac arrest). Models using CAC volume and density resulted in improvement in the C-index (0.703, SE 0.012 versus 0.687, SE 0.013) and a significant net reclassification improvement (0.208 [95% CI, 0.102-0.306]) compared with the Agatston score for CHD risk prediction. Density was significantly associated with lower CHD risk at volumes ≤130 mm3 (hazard ratio, 0.57 per unit of density [95% CI, 0.43-0.75]), but the inverse association at volumes >130 mm3 was not significant (hazard ratio, 0.82 per unit of density [95% CI, 0.55-1.22]). CONCLUSIONS: The lower risk for CHD associated with higher CAC density varied by level of volume, and volume ≤130 mm3 is a potentially clinically useful cut point. Further study is needed to integrate these findings into a unified CAC scoring method.

Association of Coronary Artery Calcium Density and Volume With Predicted Atherosclerotic Cardiovascular Disease Risk and Cardiometabolic Risk Factors in South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

Individuals of South Asian (SA) ancestry are predisposed to a higher risk of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC) volume and density can identify coronary plaque characteristics unique to SA that may provide important prognostic information to identify high risk individuals beyond traditional CAC scores. We used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA). CAC density and volume were assessed according to established protocols. ASCVD risk was estimated using the pooled cohort equations (PCE). Multivariable-adjusted linear regression models were used to study the association between the PCE and advanced CAC measures, and between cardiovascular risk factors and CAC density and volume. Our analyses included 1,155 participants (mean age 57 (SD 9) years, 52% men) with information on advanced CAC measures. After multivariable-adjustment, the PCE was associated with both CAC density (ß 0.24, 95% CI 0.12,0.35) and CAC volume (ß 0.43, 95% CI 0.38,0.48). High-density lipoprotein cholesterol was directly associated with CAC density while waist circumference was inversely associated with it. Body mass index, hypertension status, statin use, diabetes, and HOMA-IR were all directly associated with CAC volume. Estimated ASCVD risk was associated with both CAC volume and density. Different cardiometabolic risk factors are associated with CAC density and volume. Future longitudinal studies are required to demonstrate the interrelationship of advanced CAC measures and cardiovascular risk factors with incident ASCVD outcomes.

Inter-arm systolic blood pressure difference: non-persistence and association with incident cardiovascular disease in the Multi-ethnic Study of Atherosclerosis.

We investigated inter-arm systolic blood pressure (sIAD) difference, reproducibility, and incident cardiovascular disease (CVD). We hypothesized that higher sIAD values have low prevalence and nonpersistence over years, but that CVD risk is higher starting from the time of first high absolute sIAD. In Multi-Ethnic Study of Atherosclerosis participants (n = 6725, 53% female, 45-84 years old), Doppler systolic blood pressure (SBP) measurements were made in both arms (10-minute interval) thrice over 9.5 years. Proportional hazards for CVD (coronary heart disease, heart failure, stroke, peripheral arterial disease (PAD)) over 16.4 years were tested according to time-varying absolute inter-arm difference with covariates: (1) age, gender, race, and clinic; (2) model 1 plus height, heart rate, BP, antihypertensives, BMI, smoking status, lipids, lipid lowering medication, and diabetes. High sIAD was not persistent across exams. Maximum absolute sIAD ≥ 15 mmHg was found at least once in 815 persons. Maximum absolute sIAD had a graded relationship with incident stroke or PAD: 6.2% events; model 2 hazard ratio per 10 mmHg 1.34 (95% CI, 1.15-1.56) and this risk was approximately doubled for maximum absolute sIAD ≥ 15 mmHg vs 0-4 mmHg. Total CVD risk (18.4% events) was increased only for maximum absolute sIAD ≥25 mmHg. Associations with incident CVD did not differ for higher SBP in left vs right arm. A higher maximum absolute sIAD at any exam was associated with greater risk for stroke and PAD especially for values ≥ 15 mmHg, and ≥25 mmHg for other CVD. Measuring SBP between arms may help identify individuals at risk for CVD.

Barriers to participation in supervised exercise therapy reported by people with peripheral artery disease.

OBJECTIVE: This study identified barriers to participation in supervised exercise therapy covered by the Centers for Medicare and Medicaid Services (CMS), reported by people with lower extremity peripheral artery disease (PAD). METHODS: People with PAD participating in research studies of walking impairment due to PAD in the Chicagoland area were asked to complete a questionnaire between March 15, 2019, and July 12, 2022, assessing their experience and attitudes about supervised exercise therapy. Participants were identified using mailed postcards to people aged 50 and older in Chicagoland, from medical centers in Chicago, and using bus and train advertisements. The questionnaire was developed based on focus group feedback from people with PAD. RESULTS: Of 516 participants with PAD approached, 489 (94.8%) completed the questionnaire (mean age: 71.0 years [standard deviation: 8.7], mean ankle-brachial index: 0.71 [standard deviation: 0.25]; 204 [41.7%] women and 261 [53.4%] Black). Of the 489 participants, 416 (85.1%) reported that their physician had never prescribed or recommended supervised exercise therapy. Overall, 357 (73.2%) reported willingness to travel three times weekly to the medical center for supervised exercise participation. However, of these, 214 (59.9%) reported that they were unwilling or unable to pay the $11 per exercise session copay required for supervised exercise covered by CMS. Of 51 people with PAD who reported prior participation in supervised exercise, only 5 (9.8%) completed the 12 weeks of supervised exercise therapy covered by CMS and 29 (56.9%) completed 6 or fewer weeks. Of 131 (26.8%) unwilling to travel three times weekly to a center for supervised exercise, the most common reasons for unwillingness to participate were "too time-consuming" (55.0%), "too inconvenient" (45.8%), and "lack of interest in treadmill exercise" (28.2%). CONCLUSIONS: Approximately 2 to 4 years after CMS began covering supervised exercise for PAD, most people with PAD in this study from a large urban area had not participated in supervised exercise therapy. Of those who participated, most completed fewer than half of the sessions covered by CMS. The required CMS copayment was a common barrier to supervised exercise participation by people with PAD.