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Background: One strategy to reduce the burden of cardiovascular disease is the early detection and treatment of atherosclerosis. This has led to significant interest in studies of subclinical atherosclerosis, using different phenotypes, not all of which are accurate reflections of the presence of asymptomatic atherosclerotic plaques. The aim of part 2 of this series is to provide a review of the existing literature on purported measures of subclinical disease and recommendations concerning which tests may be appropriate in the prevention of incident cardiovascular disease., Methods: We conducted a critical review of measurements used to infer the presence of subclinical atherosclerosis in the major conduit arteries and focused on the predictive value of these tests for future cardiovascular events, independent of conventional cardiovascular risk factors, in asymptomatic people. The emphasis was on studies with >10 000 person-years of follow-up, with meta-analysis of results reporting adjusted hazard ratios (HRs) with 95% CIs. The arterial territories were limited to carotid, coronary, aorta, and lower limb arteries., Results: In the carotid arteries, the presence of plaque (8 studies) was independently associated with future stroke (pooled HR, 1.89 [1.04-3.44]) and cardiac events (7 studies), with a pooled HR, 1.77 (1.19-2.62). Increased coronary artery calcium (5 studies) was associated with the risk of coronary heart disease events, pooled HR, 1.54 (1.07-2.07) and increasing severity of calcification (by Agaston score) was associated with escalation of risk (13 studies). An ankle/brachial index (ABI) of <0.9, the pooled HR for cardiovascular death from 7 studies was 2.01 (1.43-2.81). There were insufficient studies of either, thoracic or aortic calcium, aortic diameter, or femoral plaque to synthesize the data based on consistent reporting of these measures., Conclusions: The presence of carotid plaque, coronary artery calcium, or abnormal ankle pressures seems to be a valid indicator of the presence of subclinical atherosclerosis and may be considered for use in biomarker, Mendelian randomization and similar studies., Competing Interests: Disclosures None.

We determined associations of cumulative exposures to neighborhood physical activity opportunities with risk of incident cardiovascular disease (CVD). We included 3595 participants from the Cardiovascular Health Study recruited between 1989 and 1993 (mean age = 73; 60% women; 11% black). Neighborhood environment measures were calculated using Geographic Information Systems (GIS) and annual information from the National Establishment Time Series database, including the density of (1) walking destinations and (2) physical activity/recreational facilities in a 1- and 5-km radius around the respondent's home. Incident CVD was defined as the development of myocardial infarction, stroke, or cardiovascular death and associations with time to incident CVD were estimated using Cox proportional hazards models. A total of 1986 incident CVD cases occurred over a median follow-up of 11.2 years. After adjusting for baseline and time-varying individual and neighborhood-level confounding, a one standard deviation increase in walking destinations and physical activity/recreational facilities within 5 km of home was associated with a respective 7% (95% confidence interval (CI) = 0.87-0.99) and 12% (95% CI = 0.73-1.0) decreased risk of incident CVD. No significant associations were noted within a 1-km radius. Efforts to improve the availability of physical activity resources in neighborhoods may be an important strategy for lowering CVD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Prospective studies reporting a positive association of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with incident cardiovascular disease (CVD) have included primarily white individuals. We evaluated associations of Lp-PLA2 and first-time cardiovascular events in a healthy multi-ethnic cohort characterized by presence or absence of baseline subclinical atherosclerosis., Methods: Lp-PLA2 mass and activity were measured at baseline in 5456 participants in the Multi-Ethnic Study of Atherosclerosis. Individuals were characterized for presence of baseline subclinical disease (coronary artery calcium score > 0 or carotid intima-media thickness value > 80th percentile) and followed prospectively for development of CVD events (coronary heart disease, ischemic stroke, and cardiovascular death)., Results: 516 incident CVD events occurred over median follow-up of 10.2 years. In adjusted Cox proportional hazards models, each higher standard deviation of both Lp-PLA2 activity and mass was associated with an increased risk of cardiovascular events; hazard ratios (HR; 95% confidence intervals (CI)) 1.12 (1.01-1.26) for Lp-PLA2 activity and 1.10 (1.01-1.21) for mass. Associations did not differ by subclinical disease status (p-value for interaction 0.99 for Lp-PLA2 activity and 0.32 for Lp-PLA2 mass) and there was no confounding by subclinical atherosclerosis measures. Associations of Lp-PLA2 activity but not mass were weaker in Chinese participants but there were relatively few events among Chinese in race-stratified analysis., Conclusion: In this multi-ethnic cohort, Lp-PLA2 was positively associated with CVD risk, regardless of the presence of coronary artery calcium or a thickened carotid-intimal media., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Vascular surgery is associated with a higher incidence of perioperative cardiovascular morbidity and mortality compared with other noncardiac surgeries. Patients undergoing vascular surgery represent a higher-risk population, usually because of the presence of generalized arterial disease and multiple comorbidities. The overwhelming perioperative cardiac event is myocardial infarction. This article offers a tailored approach to preoperative cardiovascular management for patients undergoing vascular surgery. The use and limitations of well-established guidelines and clinical risk indices for patients undergoing noncardiac surgery are described as it pertains to vascular surgery in particular. Furthermore, the role and benefit of noninvasive stress testing, coronary revascularization, and medical therapy before vascular surgery are discussed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

• CMEC quantifies net movement of cholesterol between cells and HDL. • We determined the association of CMEC with CAC. • Higher CMEC levels were not associated with lower CAC score or higher CAC density. • CV risk associated with HDL CMEC appears unrelated to calcified plaque burden. We assessed the cross-sectional and longitudinal relationships of high-density lipoprotein (HDL)-mediated cholesterol mass efflux capacity (CMEC) with coronary artery calcium (CAC) score and CAC density. CMEC was measured in 1626 Multi-Ethnic Study of Atherosclerosis (MESA) participants in samples obtained between 2000 and 2002 as part of two nested case-control studies, one with cases of incident cardiovascular disease and the other with cases of carotid plaque progression by ultrasound. Cardiac CT examinations for the presence of CAC were performed at baseline and at two additional examinations. CAC scores (Agatston and volume) and density scores (for those with positive CAC) were calculated. Multivariable linear regression modeling per SD increment of CMEC was used to estimate the associations of CMEC with each of these CAC measures. We found no association between higher CMEC and either lower CAC scores or a higher CAC density. We also found no association between higher CMEC and progression of any of these CAC measures. These findings suggest that HDL-mediated cholesterol efflux may be associated with cardiovascular risk via mechanisms unrelated to burden of calcified plaque. [ABSTRACT FROM AUTHOR]

We investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle–brachial index (ABI). Hs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15 from baseline, was assessed among 5920 eligible individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3–10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively. Overall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes. NT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD. • Hs-cTnT and NT-proBNP levels are associated with an increased risk of PAD in predominantly white populations. • We expanded these findings to a multi-ethnic cohort without baseline cardiovascular disease. • Future studies are needed to determine whether these biomarkers can actually improve PAD risk prediction. [ABSTRACT FROM AUTHOR]

Background: Current literature examining the prospective relation of circulating omega-3 (n-3) and omega-6 (n-6) PUFAs and atrial fibrillation (AF) is limited to predominantly white populations.Objectives: We investigated the association of circulating n-3 and n-6 PUFAs with incident AF in participants from the Multi-Ethnic Study of Atherosclerosis.Methods: A total of 6229 participants (mean age = 62 y; 53% female; 39% white, 27% black, 22% Hispanic, and 12% Chinese) who were free of baseline AF and with plasma phospholipid PUFAs measured at baseline using GC were prospectively followed for the development of AF. Incident AF was ascertained using International Classification of Diseases-9 codes from hospital discharge records and Medicare claims data with follow-up through 2014. Multivariable Cox proportional hazards regression analysis was performed to determine the risk of incident AF.Results: During a median follow-up of 12.9 y, 813 (13%) participants developed AF. Each higher SD increment in arachidonic acid (AA; 20:4n-6) concentrations was associated with an 11% decreased risk of incident AF (HR: 0.89; 95% CI: 0.82, 0.96). Similarly, higher overall n-6 PUFA concentrations were also associated with a reduced AF risk (HR per SD increment: 0.93; 95% CI: 0.87, 1.00). Although no significant overall associations were observed for any individual n-3 PUFAs, higher circulating concentrations of DHA (22:6n-3) and EPA (20:5n-3) were associated with a decreased AF risk in blacks and Hispanics (DHA only) but not whites or Chinese Americans.Conclusions: In a multiethnic cohort of individuals free of baseline cardiovascular disease, higher plasma concentrations of n-6 PUFAs, particularly AA, were associated with a reduced risk of incident AF. Important differences in AF risk were also noted across race/ethnicity for the n-3 PUFAs DHA and EPA. [ABSTRACT FROM AUTHOR]

Background: Endothelial dysfunction is associated with common risk factors for AF and has been implicated in the pathophysiology of atrial fibrillation (AF) through a variety of mechanisms. We determined the prospective association of brachial flow-mediated dilation (FMD) with incident AF among older adults.Methods: We included 2027 Cardiovascular Health Study participants (mean age=78.3 years, male=39%, Black=17%) who underwent brachial FMD measurement at the 1997 to 1998 clinic visit. Incident AF was ascertained by study electrocardiograms, hospital discharge diagnosis coding and Medicare claims data. Cox regression models were used to examine the association between FMD and incident AF.Results: We identified 754 incident of AF cases (37%) over a median follow-up of 11.0 years. After adjusting for age, sex, race, height, weight, cardiovascular disease, cigarette smoking, hypertension, diabetes, kidney function, c-reactive protein, physical activity, alcohol consumption, and statins, the risk of AF did not differ according to brachial FMD response (4th vs 1st quartile hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.81, 1.26; per FMD unit increment HR=1.01, 95% CI: 0.97, 1.05).Conclusion: We found no relationship between brachial FMD and the risk of developing AF in this elderly cohort. Our findings suggest that the utility of brachial FMD as a risk marker for AF in older individuals is minimal. [ABSTRACT FROM AUTHOR]

Prospective studies supporting a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident peripheral arterial disease (PAD) are limited. We evaluated the association of Lp-PLA2 with incident PAD in a multi-ethnic cohort without clinical cardiovascular disease. A total of 4622 participants with measurement of Lp-PLA2 mass and Lp-PLA2 activity and an ankle–brachial index (ABI) between 0.9 and 1.4 were followed for the development of PAD (median follow-up = 9.3 years), defined as an ABI ⩽0.9 and decline from baseline ⩾0.15. There were 158 incident PAD events during follow-up. In adjusted logistic regression models, each higher standard deviation of both Lp-PLA2 activity and mass did not confer an increased risk of developing PAD [odds ratios, (95% confidence intervals)]: 0.92 (0.66–1.27) for Lp-PLA2 activity and 1.06 (0.85–1.34) for mass. Additionally, no significant interaction was found according to ethnicity: p=0.43 for Lp-PLA2 activity and p=0.55 for Lp-PLA2 mass. We found no evidence of an association between Lp-PLA2 and incident PAD. [ABSTRACT FROM AUTHOR]

Mechanisms underlying the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) in atherosclerotic development are not completely understood. We evaluated the relationship of Lp-PLA2 with endothelial dysfunction, an early manifestation of atherosclerosis, in a cohort without known clinical cardiovascular disease. A total of 2809 participants in the Multi-Ethnic Study of Atherosclerosis underwent plasma Lp-PLA2 mass and activity measurement and brachial artery flow-mediated vasodilation testing. In adjusted linear regression models, higher Lp-PLA2 mass and activity levels were not associated with lower endothelial function (−0.04%, p = 0.51 and −0.09%, p = 0.10, respectively). Among individuals with subclinical atherosclerosis based on ankle–brachial index (ABI) or carotid intima–media thickness (IMT), Lp-PLA2 mass and activity were not associated with lower endothelial function (−0.03%, p = 0.88 and −0.31%, p = 0.16 for ABI < 1.00; 0.01%, p = 0.94 and −0.15%, p = 0.20 for abnormal carotid IMT). In summary, Lp-PLA2 is not associated with endothelial dysfunction, suggesting its role in atherosclerosis development is primarily related to other factors. [ABSTRACT FROM AUTHOR]

Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship. We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline. Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm3/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm3/year in quartile 4, compared to −3.44, −0.59 and 1.91 mm3/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL. Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression. • Higher Lp(a) was related to a higher annual absolute increase in CAC volume. • The relationship was stronger in participants with inflammation and procoagulation. • Baseline Lp(a) was not related to change in the density of CAC. [ABSTRACT FROM AUTHOR]