Assessment of Subclinical Atherosclerosis in Asymptomatic People In Vivo: Measurements Suitable for Biomarker and Mendelian Randomization Studies.

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.

Omega-3 Polyunsaturated Fatty Acids are not associated with Peripheral Artery Disease in a Meta-Analysis from the Multi-Ethnic Study of Atherosclerosis and Atherosclerosis Risk in Communities Study Cohorts.

BACKGROUND: Research suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce. OBJECTIVES: We evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts. METHODS: Omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined. RESULTS: In the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y. CONCLUSION: This study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk.

Association of diabetes and glycemic control with left atrial function: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND AIMS: Although glycemic status is associated with impaired cardiac structure and function, less is known on left atrial (LA) function across the glycemic spectrum. We evaluated the association of diabetes and glycemic control with LA function in a community-based cohort of older adults. METHODS AND RESULTS: This cross-sectional analysis included 5075 participants from the Atherosclerosis Risk in Communities Study (mean age 75.5 years, 58 % women, and 20 % Black adults) with echocardiographic strain data for LA reservoir, conduit, and contractile function. Multivariable linear regression was used to assess associations of diabetes status and glycemic control with LA function. In participants without diabetes, we used ordinal linear regression to evaluate associations of fasting glucose and HbA1c with LA function. Compared to individuals with a normal fasting glucose, prevalent diabetes was associated with 0.68 % lower LA conduit function (95 % confidence interval (CI): 1.11 to -0.25) and prediabetes a 0.47 % reduction (95 % CI: 0.85 to -0.09) in fully adjusted analyses. Persons with diabetes and high HbA1c (HgbA1c ≥ 7 % vs <7 %) had 1.05 % lower LA conduit function (95 % CI: 1.63, -0.48). Among individuals without diagnosed diabetes, higher fasting glucose, but not HbA1c, was significantly associated with worse LA conduit function. No significant associations were observed for LA reservoir and contractile function. CONCLUSIONS: A history of diabetes, prediabetes, and higher fasting glucose levels in persons without diabetes were associated with worse LA conduit function. Corroborative research is needed in prospective cohorts as well as studies that explore underlying mechanisms.

Oral factor Xa inhibitor underutilization following lower extremity peripheral vascular intervention.

OBJECTIVE: Patients undergoing peripheral vascular intervention (PVI) (ie, endovascular revascularization) for symptomatic lower extremity peripheral artery disease remain at high risk for major adverse limb and cardiovascular events. High-quality evidence demonstrates the addition of a low-dose oral factor Xa inhibitor to single antiplatelet therapy, termed dual pathway inhibition (DPI), reduces the incidence of major adverse events in this population. This study aims to describe the longitudinal trends in factor Xa inhibitor initiation after PVI, identify patient and procedural characteristics associated with factor Xa inhibitor use, and describe temporal trends in antithrombic therapy post-PVI before vs after VOYAGER PAD. METHODS: This retrospective cross-sectional study was performed using data from the Vascular Quality Initiative PVI registry from January 2018 through June 2022. Multivariate logistic regression was utilized to determine predictors of factor Xa inhibitor initiation following PVI, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 91,569 PVI procedures were deemed potentially eligible for factor Xa inhibitor initiation and were included in this analysis. Overall rates of factor Xa inhibitor initiation after PVI increased from 3.5% in 2018 to 9.1% in 2022 (P < .0001). The strongest positive predictors of factor Xa inhibitor initiation after PVI were non-elective (OR, 4.36; 95% CI, 4.06-4.68; P < .0001) or emergent (OR, 8.20; 95% CI, 7.14-9.41; P < .0001) status. The strongest negative predictor was postoperative dual antiplatelet therapy prescription (OR, 0.20; 95% CI, 0.17-0.23; P < .0001), highlighting significant hesitation about use of DPI after PVI and limited translation of VOYAGER PAD findings into clinical practice. Antiplatelet medications remain the most common antithrombotic regimen after PVI, with almost 70% of subjects discharged on dual antiplatelet therapy and approximately 20% discharged on single antiplatelet therapy. CONCLUSIONS: Factor Xa inhibitor initiation after PVI has increased in recent years, although the absolute rate remains low, and most eligible patients are not prescribed this treatment.

Statin therapy is associated with improved perioperative outcomes and long-term mortality following carotid revascularization in the Vascular Quality Initiative.

OBJECTIVE: Statin therapy is the standard of care for patients with carotid artery stenosis given its proven cardiovascular benefits. However, the impact of statin therapy on outcomes in patients undergoing carotid revascularization in the Vascular Quality Initiative has not yet been evaluated. Therefore, our aim was to investigate the association of statin therapy with outcomes following carotid endarterectomy (CEA), transfemoral carotid artery stenting (tfCAS), and transcarotid artery revascularization (TCAR). METHODS: We identified all patients who underwent CEA, tfCAS, or TCAR in the Vascular Quality Initiative registry from January 2016 to September 2021. To compare outcomes, we stratified patients by procedure type and created 1:1 propensity score-matched cohorts of patients who received no preoperative statin therapy (within 36 hours of procedure) versus those who received preoperative statin therapy. Propensity scores incorporated demographic characteristics, comorbidities, carotid symptom status, preoperative medications, and physician and hospital procedural experience. The primary outcome was a composite end point of in-hospital stroke and/or death. As a secondary analysis, we performed repeat propensity score-matching by postoperative statin use (prescribed at discharge) and assessed 5-year mortality. Relative risks (RR) and hazard ratios (HR) were calculated using log binomial regression and Cox regression, respectively. RESULTS: Among 97,835 CEA, 20,303 tfCAS, and 22,371 TCAR patients, 15%, 17%, and 10% of patients did not receive preoperative statin therapy, respectively. Compared with statin use, no statin use was associated with a higher risk of in-hospital stroke or death among 13,434 matched CEA patients (no statin, 1.7% vs statin, 1.4%; RR, 1.2; 95% confidence interval [CI], 1.02-1.5) and among 2707 matched tfCAS patients (4.8% vs 2.8%; RR, 1.7; 95% CI, 1.3-2.3). However, there was no difference for this outcome by statin use among 2089 matched TCAR patients (1.8% vs 1.6%; RR, 1.1; 95% CI, 0.7-1.8). At 5 years, no statin therapy at discharge was associated with higher 5-year mortality after CEA (15% vs 10%; HR, 1.8; 95% CI, 1.6-2) and tfCAS (18% vs 14%; HR, 1.5; 95% CI, 1.2-1.8), but there was no difference after TCAR (14% vs 11%; HR, 1.3; 95% CI, 0.9-1.8). CONCLUSIONS: Compared with statin use, no statin use was associated with a higher risk of in-hospital stroke or death and 5-year mortality among CEA and tfCAS patients. Although there was no significant difference in outcomes among TCAR patients, this may in part be due to lower statistical power in this cohort. Overall, statin therapy is essential in the short- and long-term management of patients undergoing carotid revascularization. Our findings not only support current Society for Vascular Surgery recommendations for statin therapy in patients undergoing carotid revascularization, but they also highlight an important opportunity for quality improvement.

Associations of dietary patterns with risk of incident atrial fibrillation in the REasons for Geographic And Racial Differences in Stroke (REGARDS).

BACKGROUND: We examined whether the risk of incident atrial fibrillation (AF) in a large, biracial, prospective cohort is lower in participants who adhere to heart-healthy dietary patterns and higher in participants who adhere to less heart-healthy diets. METHODS: Between 2003 and 2007, the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study enrolled 30,239 Black and White Americans aged 45 years or older. Dietary patterns (convenience, plant-based, sweets, Southern, and alcohol and salads) and the Mediterranean diet score (MDS) were derived based on food frequency questionnaire data. The primary outcome was incident AF at the follow-up visit 2013-2016, defined by either electrocardiogram or self-reported medical history of a physician diagnosis. RESULTS: This study included 8977 participants (mean age 63 ± 8.3 years; 56% women; 30% Black) free of AF at baseline who completed the follow-up exam an average of 9.4 years later. A total of 782 incident AF cases were detected. In multivariable logistic regression analyses, neither the MDS score (odds ratio (OR) per SD increment = 1.03; 95% confidence interval (CI) 0.95-1.11) or the plant-based dietary pattern (OR per SD increment = 1.03; 95% CI 0.94-1.12) were associated with AF risk. Additionally, an increased AF risk was not associated with any of the less-healthy dietary patterns. CONCLUSIONS: While specific dietary patterns have been associated with AF risk factors, our findings fail to show an association between diet patterns and AF development.

Glucose dysregulation and subclinical cardiac dysfunction in older adults: The Cardiovascular Health Study.

OBJECTIVE: We evaluated whether measures of glucose dysregulation are associated with subclinical cardiac dysfunction, as assessed by speckle-tracking echocardiography, in an older population. METHODS: Participants were men and women in the Cardiovascular Health Study, age 65+ years and without coronary heart disease, atrial fibrillation, or heart failure at baseline. We evaluated fasting insulin resistance (IR) with the homeostatic model of insulin resistance (HOMA-IR) and estimated the Matsuda insulin sensitivity index (ISI) and insulin secretion with an oral glucose tolerance test. Systolic and diastolic cardiac mechanics were measured with speckle-tracking analysis of echocardiograms. Multi-variable adjusted linear regression models were used to investigate associations of insulin measures and cardiac mechanics. RESULTS: Mean age for the 2433 included participants was 72.0 years, 33.6% were male, and 3.7% were black. After adjustment for age, sex, race, site, speckle-tracking analyst, echo image and quality score, higher HOMA-IR, lower Matsuda ISI, and higher insulin secretion were each associated with worse left ventricular (LV) longitudinal strain and LV early diastolic strain rate (p-value < 0.005); however, associations were significantly attenuated after adjustment for waist circumference, with the exception of Matsuda ISI and LV longitudinal strain (increase in strain per standard deviation increment in Matsuda ISI = 0.18; 95% confidence interval = 0.03-0.33). CONCLUSION: In this cross-sectional study of older adults, associations of glucose dysregulation with subclinical cardiac dysfunction were largely attenuated after adjusting for central adiposity.

Functional performance status and risk of cardiovascular events and mortality following endovascular repair of thoracic and abdominal aortic pathology.

OBJECTIVE: To characterize the association of preoperative functional performance status based on Eastern Cooperative Oncology Group (ECOG) scoring with the risk of adverse cardiovascular events, vascular events, and mortality in patients undergoing EVAR and TEVAR. METHODS: Retrospective review of the Society for Vascular Surgery Vascular Quality Initiative, a large, multi-center, registry database was performed. All individuals undergoing EVAR (n = 18,730) and TEVAR (n = 6595) for non-ruptured aortic pathologies between 2014 and 2018 were eligible for analysis. Multivariable logistic regression was used to determine the association of pre-procedure ECOG functional performance status on risk of in-hospital adverse cardiovascular events, vascular events, and mortality. RESULTS: The number of operations complicated by adverse cardiovascular and vascular events was 480 (2.6%) and 190 (1.0%) for EVAR and 733 (11.1%) and 219 (3.3%) for TEVAR, respectively. There were 118 (0.6%) and 240 (3.6%) in-hospital deaths following EVAR and TEVAR, respectively. Patients with ECOG grades 3 or 4 undergoing EVAR were at increased risk of cardiovascular events (OR = 1.62; 95% CI = 1.09, 2.41) and one-year mortality (HR = 2.62; 95% CI = 1.92, 3.57) compared to those with ECOG grade 0. Patients undergoing TEVAR with ECOG grade 3 or 4 were at increased risk for both inpatient death (OR = 2.77; 95% CI = 1.56, 4.9) and one-year mortality (HR = 3.27, 95% CI = 2.06, 5.21). ECOG status was not associated with an increased risk of adverse vascular events following either EVAR or TEVAR. CONCLUSIONS: Poor preoperative functional status as assessed by ECOG score is associated with an increased risk of adverse postoperative cardiovascular events following EVAR and a higher mortality risk following both EVAR and TEVAR. Functional status assessment may be useful for risk stratification and determining procedural candidacy prior to EVAR and TEVAR.

Associations of body size and composition with subclinical cardiac dysfunction in older individuals: the cardiovascular health study.

BACKGROUND: Focused studies in younger to middle-aged populations have demonstrated a relationship between obesity and adverse cardiac mechanics. We examined whether measures of overall and central adiposity are associated with cardiac mechanics, assessed by speckle-tracking echocardiography, in an older population without prevalent coronary heart disease or heart failure. METHODS: Body composition was measured by anthropometry, bioelectrical impedance, and dual-energy x-ray absorptiometry among participants in the Cardiovascular Health Study, a population-based cohort of adults aged 65 years or older. Systolic and diastolic cardiac mechanics were measured with speckle-tracking analysis of echocardiograms. Multi-variable adjusted linear regression models were used to investigate associations of body composition measures and cardiac mechanics. RESULTS: Mean age for the 3525 included participants was 72.6 years, 39% were male, and 10% were black. Mean body-mass index (BMI) was 26.3 ± 4.4 kg/m2, waist circumference (WC) was 93.2 ± 12.9 cm, and waist-to-hip ratio was 0.92 ± 0.09. In fully adjusted analyses, all adiposity measures were associated with worse LV longitudinal strain, LV early diastolic strain rate, and left atrial reservoir strain; however, associations were strongest for WC and BMI (p < 0.001). When both BMI and WC were included in the same model, only WC remained associated with each cardiac strain measure. CONCLUSION: In this cross-sectional study of older adults, central obesity was most robustly associated with impaired left ventricular systolic and diastolic strain as well as left atrial strain. The adverse effects of central obesity appear to extend even into older age.

Plasma ω-3 and ω-6 PUFA Concentrations and Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.

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.

Soluble CD14 and Risk of Heart Failure and Its Subtypes in Older Adults.

BACKGROUND: CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults. METHODS AND RESULTS: We included participants in the Cardiovascular Health Study without preexisting HF and available baseline sCD14. We evaluated the associations of sCD14, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and white blood cell count (WBC) with incident HF and subtypes using Cox regression. Among 5217 participants, 1878 had incident HF over 13.6 years (609 classifiable as HF with preserved ejection fraction [HFpEF] and 419 as HF with reduced ejection fraction [HFrEF]). After adjusting for clinical and laboratory covariates, sCD14 was significantly associated with incident HF (hazard ratio [HR]: 1.56 per doubling, 95% confidence interval [CI]: 1.29-1.89), an association that was numerically stronger than for hsCRP (HR per doubling: 1.10, 95% CI: 1.06-1.15), IL-6 (HR: 1.18, 95% CI: 1.10-1.25), and WBC (HR: 1.24, 95% CI: 1.09-1.42), and that remained significant after adjustment for the other markers of inflammation. This association for sCD14 was observed with HFpEF (HR: 1.50, 95% CI: 1.07-2.10) but not HFrEF (HR: 0.99, 95% CI: 0.67-1.49). CONCLUSIONS: Plasma sCD14 was associated with incident HF independently and numerically more strongly than other major inflammatory markers. This association was only observed with HFpEF in the subset with classifiable HF subtypes. Pending replication, these findings have potentially important therapeutic implications.

Brachial Flow-mediated Dilation and Risk of Dementia: The Cardiovascular Health Study.

INTRODUCTION: Brachial flow-mediated dilation (FMD) is a physiologic measure of endothelial function. We determined the prospective association of brachial FMD with incident dementia among older adults. METHODS: We included 2777 Cardiovascular Health Study participants who underwent brachial FMD measurement. Incident dementia was ascertained by medication use, International Classification of Diseases-9 codes, requirement for a proxy, and death certificates and calibrated to gold-standard assessments performed in a subset of the cohort. RESULTS: Mean participant age at time of brachial FMD measurement was 77.9 years. We identified 1650 incident dementia cases (median follow-up=10.5 y). After adjusting for age, race, sex, education, clinic site, and baseline arterial diameter, risk of dementia for participants in the highest quartile of percent brachial FMD did not differ from those in lowest quartile (hazard ratio=0.89, 95% confidence interval: 0.77, 1.03). CONCLUSIONS: Brachial FMD, measured late in life, is not associated with an increased risk of incident dementia.

Preoperative hemoglobin A1c levels and increased risk of adverse limb events in diabetic patients undergoing infrainguinal lower extremity bypass surgery in the Vascular Quality Initiative.

BACKGROUND: The impact of preoperative glycemic control on the risk of adverse perioperative outcomes in diabetic patients undergoing lower extremity bypass (LEB) surgery is not well-understood. We determined whether higher preoperative hemoglobin A1c (HbA1c) levels are associated with an increased risk of major adverse limb events, major adverse cardiovascular events, and mortality in diabetic patients undergoing infrainguinal LEB. METHODS: A retrospective review of all infrainguinal LEB surgeries in the Vascular Quality Initiative registry from January 2012 to February 2017 was performed. Only surgeries performed on diabetic patients with complete demographic and clinical data, including HbA1c value at the time of LEB, were included for analysis (n = 7727). Entries were stratified according to the following HbA1c levels: 6 or less (n = 1087), greater than 6 to 7 or less (n = 2137), greater than 7 to 8 or less (n = 1657), and greater than 8 (n = 2846). Multivariate logistic regression was used to determine the association of preoperative HbA1c levels on the risk of in-hospital major adverse limb events (above ankle amputation, loss of primary graft patency), major adverse cardiovascular events (myocardial infarction, stroke, congestive heart failure, cardiac arrhythmia), and mortality. RESULTS: The number of surgeries complicated by adverse limb and cardiovascular events were 356 (4.6%) and 1314 (17.0%), respectively. There were 72 in-hospital deaths (0.9%). After adjustment for clinical and demographic variables, patients with high HbA1c values (≥8%) were at an increased risk of adverse limb events (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.01-1.86) compared with those with a normal HbA1c (>6% to ≤7%). High HbA1c values were not associated with an increased risk of cardiovascular events (OR, 1.07; 95% CI, 0.81-1.43) or mortality (OR, 1.57; 95% CI, 0.83-3.03). Patients with low HbA1c values (≤6%) did not experience a significantly higher risk for any of the three outcomes. In a stratified analysis, the association of high HbA1c values with adverse limb events was only present in those presenting without critical limb ischemia (OR 1.82; 95% CI, 1.05-3.16). CONCLUSIONS: Poor preoperative glycemic control in diabetic individuals undergoing infrainguinal LEB, particularly in those without critical limb ischemia, is associated with an increased risk of in-hospital limb events. Further study should evaluate whether improved efforts to identify individuals with poorly controlled diabetes and subsequent interventions to better optimize glycemic control during the preoperative period improve limb outcomes after LEB.

Association of lipoprotein-associated phospholipase A2 and risk of incident atrial fibrillation: Findings from 3 cohorts.

BACKGROUND: Multiple prospective studies have established an association between inflammation and higher risk of atrial fibrillation (AF), but the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity and incident AF has not been extensively evaluated. METHODS: Using data from 10,794 Atherosclerosis Risk In Communities (ARIC) study participants aged 53-75 years, 5,181 Cardiovascular Health Study (CHS) participants aged 65 to 100 years, and 5,425 Multi-Ethnic Study of Atherosclerosis (MESA) participants aged 45-84 years, we investigated the association between baseline Lp-PLA2 levels and the risk of developing AF. Incident AF was identified in each cohort by follow-up visit electrocardiograms, hospital discharge coding of AF, or Medicare claims data. RESULTS: Over a mean of 13.1, 11.5, and 10.0 years of follow-up, 1,439 (13%), 2,084 (40%), and 615 (11%) incident AF events occurred in ARIC, CHS, and MESA, respectively. In adjusted analyses, each SD increment in Lp-PLA2 activity was associated with incident AF in both ARIC (hazard ratio [HR] 1.13, 95% CI 1.06-1.20) and MESA (HR 1.24, 95% CI 1.05-1.46). Each SD increment in Lp-PLA2 mass was also associated with incident AF in MESA (HR 1.25, 95% CI 1.11-1.41). No significant associations were observed among CHS participants. CONCLUSIONS: Although higher Lp-PLA2 mass and activity were associated with development of AF in ARIC and MESA, this relationship was not observed in CHS, a cohort of older individuals.

Increased risk of mortality after lower extremity bypass in individuals with acute kidney injury in the Vascular Quality Initiative.

OBJECTIVE: The development of acute kidney injury (AKI) and its effect on prognosis after lower extremity bypass (LEB) surgery have not been well described. We determined risk factors associated with AKI in patients undergoing infrainguinal LEB surgery and whether individuals with AKI are at increased risk for cardiovascular events and mortality. METHODS: Data for 12,907 operations entered in the Vascular Quality Initiative (VQI) registry from January 2012 through April 2015 were retrospectively reviewed. Procedures performed on patients not on dialysis before the surgery with perioperative assessments of renal function were eligible for the study. AKI was defined as a postoperative increase in serum creatinine ≥0.5 mg/dL or new dialysis requirement. Logistic regression was performed to determine the effect of AKI on the risk of in-hospital cardiovascular events, including myocardial infarction, stroke, congestive heart failure, or arrhythmias, and mortality. Cox proportional hazards regression was performed to determine the risk of long-term mortality (median follow-up of 11.5 months). RESULTS: AKI developed after 507 (4%) of the 12,907 operations performed in 11,859 patients. After adjustment for demographic, clinical, and perioperative variables, AKI was associated with an increased risk of in-hospital cardiovascular events (odds ratio, 2.50; 95% confidence interval [CI], 1.91-3.28) and in-hospital mortality (odds ratio, 6.96; 95% CI, 3.94-12.31). Risk of mortality persisted over the course of follow-up (hazard ratio, 1.98; 95% CI, 1.58-2.47). CONCLUSIONS: AKI after LEB is associated with an increased risk of cardiovascular events and all-cause mortality. Further study should evaluate whether preoperative interventions before LEB can be effectively applied for at-risk patients to reduce the incidence of AKI and its associated morbidity and mortality.

Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.

OBJECTIVE: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI). APPROACH AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged ≥65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95% confidence interval 1.09, 1.50). CONCLUSIONS: Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.

Lipoprotein-associated phospholipase A2 and risk of incident peripheral arterial disease in a multi-ethnic cohort: The Multi-Ethnic Study of Atherosclerosis.

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.

Association of hypertension severity and control with risk of incident atrial fibrillation: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND: The association of hypertension (HTN) severity and control with the risk of incident atrial fibrillation (AF) is unclear. HYPOTHESIS: Increased HTN severity and poorer blood pressure control would be associated with an increased risk of incident AF. METHODS: This analysis included 9485 participants (mean age 63 ± 8 years; 56% women; 35% Black). Participants were stratified into six mutually exclusive groups at baseline-normotension (n = 1629), prehypertension (n = 704), controlled HTN (n = 2224), uncontrolled HTN (n = 4123), controlled apparent treatment-resistant hypertension (aTRH) (n = 88), and uncontrolled aTRH (n = 717). Incident AF was ascertained at the follow-up visit, defined by either electrocardiogram or self-reported medical history of a physician diagnosis. Multivariable logistic regression analyses adjusted for demographic and clinical variables. RESULTS: Over an average of 9.3 years later, 868 incident AF cases were detected. Compared to those with normotension, incident AF risk was highest for those with aTRH (controlled aTRH: odds ratio (OR) 2.95; 95% confidence interval (CI) 1.60, 5.43, & uncontrolled aTRH: OR 2.47; 95% CI 1.76, 3.48). The increase in AF risk was smaller for those on no more than three antihypertensive agents regardless of their blood pressure control (controlled OR 1.72; 95% CI 1.30, 2.29 and uncontrolled OR 1.56; 95% CI 1.14, 2.13). CONCLUSIONS: The risk of developing AF is increased in all individuals with HTN. Risk is highest in those aTRH regardless of blood pressure control. A more aggressive approach that focuses on lifestyle and pharmacologic measures to either prevent HTN or better control HTN during earlier stages may be particularly beneficial in reducing related AF risk.

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.