Incident Atherosclerotic Cardiovascular Disease Events Research Articles

Associations of dietary magnesium intake with the risk of atherosclerotic cardiovascular disease and mortality in individuals with and without type 2 diabetes: A prospective study in the UK Biobank

BackgroundThe association between dietary magnesium (Mg) intake and the risk of atherosclerotic cardiovascular disease (ASCVD) remains uncertain. We aimed to examine the associations of dietary Mg intake with the risk of ASCVD events and mortality in individuals with and without type 2 diabetes. MethodsA total of 149,929 participants (4603 with type 2 diabetes) from the UK Biobank were included in the analyses. The hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models. Furthermore, interactions of dietary Mg intake with type 2 diabetes status were examined on multiplicative and additive scales. ResultsDuring a median follow-up of 12.0 and 12.1 years, 7811 incident ASCVD events and 5000 deaths (including 599 ASCVD deaths) were documented, respectively. There were significantly negative associations between sufficient dietary Mg intake (equal to or greater than the recommended daily intake) and the risk of ASCVD incidence (HR 0.63 [95 % CI 0.49;0.82]), ASCVD mortality (0.45 [0.24;0.87]), and all-cause mortality (0.71 [0.52;0.97]) in participants with type 2 diabetes, whereas no significant association was observed in participants without type 2 diabetes (1.01 [0.94;1.09] for ASCVD incidence; 1.25 [0.93;1.66] for ASCVD mortality; 0.97 [0.88;1.07] for all-cause mortality). Multiplicative and additive interactions of dietary Mg intake with type 2 diabetes status were both observed. ConclusionSufficient dietary Mg intake was significantly associated with lower risks of ASCVD events and mortality in individuals with type 2 diabetes but not in those without type 2 diabetes. Our findings provide insight into the importance of dietary Mg intake for reducing modifiable cardiovascular burden in individuals with type 2 diabetes, which may inform future personalized dietary guidelines.

Prognostic Value of Cardiovascular Biomarkers in the Population

Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

Discordance Between Very Low-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol Increases Cardiovascular Disease Risk in a Geographically Defined Cohort.

Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low-density lipoprotein cholesterol (VLDL-C) and lipid discordance could be contributors to the residual risk of ASCVD. Cardiovascular disease-free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low-density lipoprotein cholesterol (LDL-C) and VLDL-C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow-up. The association of LDL-C and VLDL-C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL-C and VLDL-C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL-C (per 10-mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05-1.09]; P<0.001]) after adjustment for traditional risk factors. The interaction between LDL-C and VLDL-C was not statistically significant (P=0.11). Discordant individuals with high VLDL-C and low LDL-C experienced the highest rate of incident ASCVD events, 16.9 per 1000 person-years, during follow-up. VLDL-C and lipid discordance are associated with a greater risk of ASCVD and can be estimated from clinically ordered lipid panels to improve ASCVD risk assessment.

Sex differences in incident atherosclerotic cardiovascular disease events among women and men with HIV: Erratum.

Sex differences in incident atherosclerotic cardiovascular disease events among women and men with HIV: Erratum.

Atherosclerotic cardiovascular disease events among adults with high predicted risk without established risk factors

ObjectiveAge is the strongest contributor to 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. Some older adults have a predicted ASCVD risk ≥7.5 %, without established risk factors. We sought to compare ASCVD incidence among adults with predicted ASCVD risk ≥7.5 %, with and without established ASCVD risk factors, to adults with predicted risk <7.5 %. MethodsWe analyzed data from REasons for Geographic and Racial Differences in Stroke study participants, 45–79 years old, without ASCVD or diabetes, not taking statins and with low-density lipoprotein cholesterol 70–189 mg/dL. Participants were categorized into 3 groups based on their 10-year predicted ASCVD risk and presence of established risk factors: <7.5 %, ≥7.5 % with established risk factors and ≥7.5 % without established risk factors. Established risk factors included smoking, systolic blood pressure ≥130 mmHg or antihypertensive medication use, total cholesterol ≥200 mg/dL, or high-density lipoprotein cholesterol <50 mg/dL for women (<40 mg/dL for men). Participants were followed for ASCVD events. ResultsAmong 11,115 participants, 911 incident ASCVD events occurred over a median of 11.1 years. ASCVD incidence rates were 3.6, 12.8, and 9.8 per 1,000 person-years for participants with predicted risk <7.5 %, predicted risk ≥7.5 % with established risk factors and predicted risk ≥7.5 % without established risk factors, respectively. Compared to adults with predicted risk <7.5 %, hazard ratios for incident ASCVD in participants with risk ≥7.5 % with and without established risk factors were 3.58 (95 %CI 3.03 – 4.21) and 2.72 (95 %CI 1.91–3.88), respectively. ConclusionsAdults with a 10-year predicted ASCVD risk ≥7.5 % but without established risk factors had a high ASCVD incidence.

Abstract 14460: Impact of Carotid Artery Plaque Detection on Cardiovascular Disease Risk and the Importance of Age in the Multi-Ethnic Study of Atherosclerosis

Background Carotid artery plaque (CAP) predicts future atherosclerotic cardiovascular disease (ASCVD) events; however, its prevalence increases with age and differs by sex and race/ethnicity, so how its presence influences ASCVD risk in clinical settings is uncertain. Hypothesis: We hypothesized that the impact of CAP detection on relative ASCVD risk declines with age. Methods: CAP was detected and quantified by ultrasound in adults free of clinical ASCVD at Exam 1 of the Multi-Ethnic Study of Atherosclerosis who were followed longitudinally for coronary death, myocardial infarction, angina, stroke, and ASCVD death. Cox proportional hazards models investigated associations of CAP and incident ASCVD events in subsets defined by age categories. These models were adjusted for confounders and an age*CAP interaction. Results: The 5198 participants were a mean (standard deviation) 61.8 (10.1) years old (53% female, 27% Black, 22% Hispanic, 12% Chinese) and experienced 880 ASCVD events over 14.3 (5.7) years. Prevalence of CAP and the age at which 50% of participants had detectable CAP differed by age, sex, and race/ethnicity, ranging from 13% in Chinese women &lt;50 years old to 97% in Non-Hispanic White men 80-84 years old (Figure). CAP presence independently predicted ASCVD events (hazard ratio, 1.35, [95% confidence interval 1.17-1.57], p&lt;0.001), however the strength of this association declined with increasing age (p interaction =0.029, Figure). CAP detection in younger individuals conferred higher relative ASCVD risk than in older participants who had higher absolute risk, regardless of CAP. Conclusions: Prevalence of CAP varies by sex and race/ethnicity. CAP becomes very common with increasing age and its relative association with future ASCVD events declines. These data can assist in guiding ASCVD risk assessment in younger adults and provide perspective for incidentally detected CAP on clinical imaging studies in older adults who have higher absolute ASCVD risk.

Abstract 12346: Atherosclerotic Cardiovascular Disease Risk Associated With Social Determinants of Health at Individual and Area Levels

Introduction: Adverse social determinants of health (SDOH) are associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD). However, it is unclear if the ASCVD risks associated with area-level SDOH are similar to those with individual-level measures. Further, SDOH are not included in the Pooled Cohort Equations (PCEs) when estimating 10-year ASCVD risk. Studies have shown that PCEs systematically underestimate risk for socially deprived individuals. Aims To examine the association of individual- and area-level SDOH including education, income, and employment with incident ASCVD. Also, we assessed if adding SDOH to the PCEs improves risk prediction accuracy. Methods: We pooled data from four cohorts: Jackson Heart Study, Multi-Ethnic Study of Atherosclerosis, Framingham Heart Study Offspring Cohort, and Reasons for Geographic and Racial Differences in Stroke Study. We excluded participants with a history of ASCVD. Individual-level SDOH were based on participants’ self-report and area-level SDOH were derived by linking participants’ addresses to US Census tract data. We used Cox proportional hazards models to assess the associations between SDOH and ASCVD. We also assessed the changes in discrimination (Harrell’s C-index) and calibration (Integrated Brier Score) after adding SDOH to risk prediction models. Results: We analyzed data from 27,603 participants (mean age 61.4 years, 59% women, and 49% White). During a median follow-up of 13 years, 2,839 incident ASCVD events occurred. Both individual- and area-level SDOH were associated with ASCVD ( Figure, Panel A ). Adding both individual- and area-level SDOH to risk prediction modestly improved model discrimination and calibration in Black men and women ( Figure, Panels B &amp; C ), and also improved calibration in non-Black women. Conclusions: The findings suggest that SDOH may be considered in the development of future ASCVD risk assessment tools, particularly among Black individuals.

Genome-Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the CETP Gene.

Background The risk of atherosclerotic cardiovascular disease (ASCVD) increases sharply with age. Some older individuals, however, remain unaffected despite high predicted risk. These individuals may carry cardioprotective genetic variants that contribute to resilience. Our aim was to assess whether asymptomatic older individuals without prevalent ASCVD carry cardioprotective genetic variants that contribute to ASCVD resilience. Methods and Results We performed a genome-wide association study using a 10-year predicted ASCVD risk score as a quantitative trait, calculated only in asymptomatic older individuals aged ≥70 years without prevalent ASCVD. Our discovery genome-wide association study of N=12 031 ASCVD event-free individuals from the ASPREE (Aspirin in Reducing Events in the Elderly) trial identified 2 independent variants, rs9939224 (P<5×10-8) and rs56156922 (P<10-6), in the CETP (cholesteryl ester transfer protein) gene. The CETP gene is a regulator of plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) levels, and it is a therapeutic drug target. The associations were replicated in the UK Biobank (subpopulation of N=13 888 individuals aged ≥69 years without prevalent ASCVD). Carriers of the identified CETP variants (versus noncarriers) had higher plasma high-density lipoprotein cholesterol levels, lower plasma low-density lipoprotein cholesterol levels, and reduced risk of incident ASCVD events during follow-up. Expression quantitative trait loci analysis predicted the identified CETP variants reduce CETP gene expression across various tissues. Previously reported associations between genetic CETP inhibition and increased risk of age-related macular degeneration were not observed among the 3917 ASPREE trial participants with retinal imaging and genetic data available. Conclusions Common genetic variants in the CETP gene region are associated with cardiovascular resilience during aging. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.

Determinants of incident atherosclerotic cardiovascular disease events among individuals with type 2 diabetic microvascular complications in the UK: a prospective cohort study

ObjectiveTo evaluate the association of atherosclerotic cardiovascular disease (ASCVD) risk factors with incident ASCVD events among type 2 diabetes (T2D) individuals with microvascular complications.MethodsWe included T2D participants with only microvascular complications from the UK Biobank cohort at baseline (2006–2010). Multivariable-adjusted Cox proportional hazards models were used to study the association between ASCVD risk factors with adjudicated incident ASCVD in T2D participants with only microvascular complications. A restricted cubic spline approach was employed to evaluate potential nonlinear associations between ASCVD risk factors and ASCVD.ResultsWe studied 4,129 T2D individuals with microvascular complications at baseline. Over a median follow-up of 11.7 years, a total of 1,180 cases of incident ASCVD were documented, of which 1,040 were CHD, 100 were stroke, and 40 were both CHD and stroke events. After multivariable-adjustment, high-density lipoprotein cholesterol (HDL-C) level was linearly associated with a decreased risk of incident ASCVD [hazard ratio (HR): 0.49, 95% Confidence interval (CI): 0.32–0.75, Plinear = 0.011] and each 10 nmol/L increase of lipoprotein(a) [Lp(a)] level (HR: 1.02, 95% CI: 1.00-1.04, Plinear = 0.012) was linearly associated with an increased risk of incident ASCVD in T2D participants with only microvascular complications.ConclusionHDL-C levels and Lp(a) levels (per 10 nmol/L) showed an independent linear relation with ASCVD risk among T2D individuals with only microvascular complications at long-term follow-up.

Prognostic value of coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with suspected nonalcoholic hepatic steatosis: Results from the multi-ethnic study of atherosclerosis

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events; thus, a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in participants with suspected nonalcoholic hepatic steatosis. A total of 713 participants with suspected nonalcoholic hepatic steatosis without previous cardiovascular events from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for the occurrence of incident ASCVD. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistics and areas under the time-dependent receiver operating characteristic curves (tAUC) were used to compare incremental contributions of CAC score when added to the clinical risk factors. In multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR=1.33, 95% CI=1.22-1.44, P < .001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (P < .001) and tAUC at 10 years from 0.668 to 0.771, respectively. In subgroup analyses, the incremental prognostic value of CAC score was more significant in participants with low/borderline- (<7.5%) and intermediate- (7.5%-20%) 10-year ASCVD risk scores. The inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with suspected nonalcoholic hepatic steatosis, indicating a potential role for CAC screening in risk assessment.

Implications of Social Disadvantage Score in Cardiovascular Outcomes and Risk Assessment: Findings From the Multi-Ethnic Study of Atherosclerosis.

Social determinants of health contribute to disparate cardiovascular outcomes, yet they have not been operationalized into the current paradigm of cardiovascular risk assessment. Data from the Multi-Ethnic Study of Atherosclerosis, which includes participants from 6 US field centers, were used to create an index of baseline Social Disadvantage Score (SDS) to explore its association with incident atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality and impact on ASCVD risk prediction. SDS, which ranges from 0 to 4, was calculated by tallying the following social factors: (1) household income less than the federal poverty level; (2) educational attainment less than a high school diploma; (3) single-living status; and (4) experience of lifetime discrimination. Cox models were used to examine the association between SDS and each outcome with adjustment for traditional cardiovascular risk factors. Changes in the discrimination and reclassification of ASCVD risk by incorporating SDS into the pooled cohort equations were examined. A total of 6434 participants (mean age, 61.9±10.2 years; female 52.8%; non-white 60.9%) had available SDS 1733 (26.9%) with SDS 0; 2614 (40.6%) with SDS 1; 1515 (23.5%) with SDS 2; and 572 (8.9%) with SDS ≥3. In total, 775 incident ASCVD events and 1573 deaths were observed over a median follow-up of 17.0 years. Increasing SDS was significantly associated with incident ASCVD and all-cause mortality after adjusting for traditional risk factors (ASCVD: per unit increase in SDS hazard ratio, 1.15 [95% CI, 1.07-1.24]; mortality: per unit increase in SDS hazard ratio, 1.13 [95% CI, 1.08-1.19]). Adding SDS to pooled cohort equations components in a Cox model for 10-year ASCVD risk prediction did not significantly improve discrimination (P=0.208) or reclassification (P=0.112). Although SDS is independently associated with incident ASCVD and all-cause mortality, it does not improve 10-year ASCVD risk prediction beyond pooled cohort equations.

Lipoprotein Apheresis: Current Recommendations for Treating Familial Hypercholesterolemia and Elevated Lipoprotein(a).

Familial hypercholesterolemia (FH) and hyperlipoproteinemia(a) are relatively common disorders, posing a significant health burden due to increased risk of atherosclerotic cardiovascular disease (ASCVD). Development of electronic health record-based strategies with a linkage to the genetic test results has increased awareness, detection, and control of heritable lipid disorders. This review attempts to critically examine available data to provide a summary of the current evidence for lipoprotein apheresis in FH and elevated lipoprotein(a) (Lp(a)). Availability and indications for lipoprotein apheresis vary across the globe. On average, greater than 60% of atherogenic apoB-containing lipoproteins are immediately reduced following a single procedure, translating in substantial reduction of incident ASCVD events, and preventing accelerated vascular aging. Simultaneous lipid-lowering therapy targeting low-density lipoprotein (LDL) and Lp(a) enhances the efficacy of lipoprotein apheresis. Lipoprotein apheresis alters the proteomics of the lipoprotein particles, including reduction in the concentration of the oxidized-LDL and Lp(a) particles, and proinflammatory apoE bound to HDL particles and remnant lipoproteins. Other effects attributed to lipoprotein apheresis include improvement in blood rheology, endothelial function, microvascular flow, myocardial perfusion, reduction in circulating inflammatory markers. Development of lipoprotein apheresis registries provides data on benefits, challenges, and barriers to inform pertinent healthcare policies. Lipoprotein apheresis is a safe and effective procedure for lowering cholesterol in patients with combined and isolated FH and elevated Lp(a). It reduces the burden of ASCVD and improves long-term prognosis. A team approach is required by the patient, medical staff, and healthcare provider to initiate and maintain a lipoprotein apheresis program.

Risk of atherosclerotic cardiovascular disease in patients with premature ASCVD: A study from approximately 1 million young adults

Abstract Funding Acknowledgements Type of funding sources: None. Background Risk of atherosclerotic cardiovascular disease (ASCVD) attributable to premature ASCVD remains poorly understood. Purpose To evaluate the risk of ASCVD among those with premature ASCVD versus those without in a large contemporary population. Methods This observational cohort study included young adults (ages 30-55 years) with and without prior ASCVD (as of January 1, 2006) who were members of an integrated healthcare delivery system in Northern California. Adjusted multivariate models were specified to estimate risk ratios (RRs) for incident ASCVD events by ASCVD status at baseline. Incident ASCVD events were defined as a composite of nonfatal myocardial infarction, ischemic stroke, or coronary heart disease death through December 31, 2020. Results A total of 929,214 individuals met the selection criteria of no prior ASCVD and 5,703 with prior ASCVD. Mean age was 43.9 (±7.3) years and 50.0 (±5.2) years, respectively. Fifty-two and thirty percent were women in each cohort, and the median follow-up was 11.8 and 8.3 years, respectively. Crude ASCVD rate was 2.1 and 24.5 events per 1,000 person-years, respectively. Age-adjusted Kaplan-Meier curves for ASCVD in individuals with and without prior ASCVD in Figure. In models adjusted for demographics (sex, age, race) and traditional risk factors (diabetes, hypertension, LDL-cholesterol, HDL-cholesterol, total cholesterol, smoking), individuals with prior ASCVD had RR of 4.6 (95% CI 4.3-5.0) for CHD, RR of 3.0 (95% CI 2.7-3.4) for stroke and RR of 4.1 (95% CI 3.8-4.3) for ASCVD. Conclusions Risk of ASCVD among those with prior ASCVD was several-fold greater compared to those without prior ASCVD. Continued efforts for secondary prevention are needed in this vulnerable high-risk population.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in Patients With Age-Related Macular Degeneration: Prospective Cohort Study of UK Biobank.

Major risk factors of atherosclerotic cardiovascular disease (ASCVD) and mortality have been well-established in the general population. Our study is aimed at assessing longitudinal relationships between ASCVD risk factors and incident ASCVD events or all-cause mortality in patients with age-related macular degeneration (AMD). Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors with adjudicated incident ASCVD events and all-cause mortality outcomes followed until 2021. A restricted cubic spline approach was utilized to assess nonlinear associations between potential cardiovascular risk factors and ASCVD or mortality. We identified 3508 eligible patients [mean (SD) age = 61.45 (6.43) years; 37.76% males] with AMD at baseline. During a median follow-up year of 12, there were 110 cases of ASCVD events and 186 cases of all-cause mortality. After multivariable adjustment, each 10 U/L increase of serum gamma-glutamyl transferase level was linearly associated with incident ASCVD [hazard ratio (HR) = 1.03, 95% CI = 1.00-1.07, Pnonlinear = 0.85)] in AMD. A history of chronic kidney disease (HR = 1.94, 95% CI = 1.09-3.46) and lower vitamin D [HR = 0.98, 95% CI = 0.97-0.99, per nanomoles per liter (nmol/L)] were significantly associated with all-cause mortality in patients with AMD, with the association between vitamin D and all-cause mortality presenting a U shape (Pnonlinear = 0.02). In contrast, risk factors significantly associated with ASCVD and all-cause mortality in healthy controls differed from patients with AMD. Our findings demonstrate risk factors associated with ASCVD events and all-cause mortality among individuals with AMD differed from healthy controls and suggest the long-term management of risk factors in patients with AMD.

Abstract P453: Apolipoprotein B, Low-Density Lipoprotein Particle Number, Non-High-Denisity Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Total Cholesterol for Atherosclerotic Cardiovascular Disease Risk Prediction in Young Adults

Introduction: Measures of atherogenic particle number (apoB and LDL particle number [LDL-P]) are stronger predictors of atherosclerotic cardiovascular disease (ASCVD) risk than measures of cholesterol concentration (LDL-C, non-HDL-C, total cholesterol [TC]) in middle-aged adults. It is unclear if this is true for younger adults. Methods: Among CARDIA participants (ppts), NMR was used to measure apoB and LDL-P. Non-HDL-C and TC were measured using standard assays; LDL-C was calculated using the Friedewald equation. We stratified the ppts into two age windows: age 20-30y (n=1645) and age 30-40y (n=2922). We used adjusted Cox proportional hazards models to assess the associations of 1SD higher apoB, LDL-P, non-HDL-C, LDL-C, or TC with incident ASCVD events. We substituted each measure of atherogenic lipid burden for TC in a modified Pooled Cohort Equation (PCE) model (with and without HDL-C); and model performance (discrimination and reclassification) was evaluated. Results: There were 81 and 163 ASCVD events over (median [IQR]) 31.8y (31.1-32.0y) for the age 20-30 age window and over 26.8y (19.1-27.1y) for the 30-40y age window, respectively. In ppts age 20-30y, a 1SD higher apoB, LDL-P, non-HDL-C, and LDL-C were significantly associated with incident ASCVD in demographic adjusted models. The strengths of associations with ASCVD were not significantly different across these measures. For the 30-40y age window, all measures of atherogenic lipoproteins were significantly associated with ASCVD; the strengths of association were not significantly different across atherogenic lipid measures in all models. There were no significant differences in the C-statistic and no improvement in reclassification when each measure was used to replace TC in the PCE model. Conclusions: ApoB, LDL-P, LDL-C or non-HDL-C may be slightly better markers of long-term ASCVD risk than TC in adults &lt; 30y. However, in adults between 30-40y all measures of atherogenic lipid burden appeared to be equivalent predictors of long-term risk.

Abstract P200: Cumulative Circulating Branched Chain Amino Acid Exposure in Young Adulthood and Incident Atherosclerotic Cardiovascular Disease (ASCVD) in Later Life: The CARDIA Study

Introduction: Circulating branched chain amino acid (BCAA) levels are associated with the development of diabetes mellitus (DM) and downstream ASCVD in middle-aged women. It is unknown if BCAAs in young adult men and women are associated with ASCVD events. BCAA levels may be dynamic in middle-aged adults prior to the development of DM or ASCVD events, thus cumulative BCAA measures in early life may better quantify exposure risk than a single measure at mid-life. Methods: We measured plasma BCAA levels in 3110 Coronary Artery Risk Development in Young Adults study participants using nuclear magnetic resonance (NMR) at Years (y) 2, 7, 15, and 20. To minimize missingness bias, BCAA levels were imputed for the residual 1835 participants without NMR measures. Cumulative BCAA exposure from 19-40y of age was calculated as the area under the curve using a spline-based mixed-effects model to estimate subject-specific BCAA trajectories from 19-40y. Sex-specific associations between cumulative BCAA exposure and incident ASCVD events after 40y of age were assessed by multivariable (Table) Cox proportional hazards regression models including BCAA levels and fasting blood glucose (FBG) at age 40y and further stratified by DM status. Results: Among 4945 participants (55.3% female), there were 255 ASCVD events and 675 DM cases over a median of 18.8 years of follow-up after age 40y. In adjusted models, cumulative BCAA exposure from 19-40y was associated with ASCVD events after 40y of age in women, but not men (Table). The associations in women were robust to adjustment for BCAAs and FBG at age 40y. There was no significant difference in the cumulative BCAA-ASCVD association among men or women who developed DM before ASCVD versus those who did not. Conclusions: Cumulative BCAA exposure in early adulthood is associated with ASCVD in women independent of mid-life BCAA levels. Elevated BCAA levels in women during early adulthood may reflect behaviors and/or metabolic pathways that increase risks for ASCVD independent of the development of hyperglycemia.

Life satisfaction and the risk of atherosclerotic cardiovascular disease in the general Japanese population: the Suita Study.

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality. Life satisfaction is a measure of mental health with a potential cardioprotective role. This study aimed to investigate the association between life satisfaction and ASCVD risk in the general Japanese population. We used data from 6,877 people (30-84 years) registered in the Suita Study, a Japanese population-based prospective cohort study. All participants were free from stroke and coronary heart disease (CHD) at baseline. Then, participants were followed up for incident ASCVD, including cerebral infarction and CHD. Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of incident ASCVD according to life satisfaction. Within 102,545 person-years (median follow-up = 16.6 years), 482 incident ASCVD events were identified. In the age- and sex-adjusted model, being very satisfied, rather satisfied, or not sure, compared to being dissatisfied with life, showed a lower risk of ASCVD: HR (95% CI) = 0.55 (0.41, 0.74), 0.67 (0.50, 0.89), and 0.57 (0.36, 0.88), respectively (p-trend < 0.001). The associations remained consistent after adjusting for stress and unfortunate events: HR (95% CI) = 0.57 (0.42, 0.77), 0.68 (0.50, 0.91), and 0.54 (0.35, 0.84), respectively (p-trend < 0.001). The results did not vary between cerebral infarction and CHD: HR (95% CI) for being very satisfied with life = 0.58 (0.37, 0.91) and 0.55 (0.36, 0.84), respectively. Life satisfaction was inversely associated with the risk of ASCVD in the investigated general Japanese population.

Stair climbing and the incidence of atherosclerotic cardiovascular disease: a population-based prospective cohort study.

Stair climbing is a readily available form of physical activity with potential cardioprotective merits. Herein, we investigated the association between stair climbing and atherosclerotic cardiovascular disease (ASCVD) incidence among Japanese people. This prospective cohort study used data from 7,282 participants, aged 30-84 years, registered in the Suita Study and free from stroke and ischemic heart disease (IHD). Standard approaches were used to detect incident ASCVD events, including cerebral infarction and IHD, during follow-up. Stair climbing was assessed using a baseline questionnaire. We applied the Cox regression to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of incident ASCVD for climbing stairs in 20-39%, 40-59%, and ≥60% compared to <20% of the time. We adjusted the regression models for age, sex, body mass index, smoking, alcohol consumption, physical activity, hypertension, diabetes, atrial fibrillation, lipid profile, chronic kidney disease, and history of cardiac murmur or valvular diseases. A total of 536 new ASCVD events were detected within a median follow-up period of 16.6 years. In the age- and sex-adjusted model, stair climbing 20-39%, 40-59%, and ≥60% of the time was associated with lower ASCVD incidence: HRs (95% CIs) = 0.72 (0.56, 0.92), 0.86 (0.68, 1.08), and 0.78 (0.61, 0.99), respectively (p-trend = 0.020). The corresponding associations were attenuated after adjusting for lifestyle and clinical factors: HRs (95% CIs) = 0.74 (0.58, 0.95), 0.90 (0.71, 1.13), and 0.89 (0.69, 1.13), respectively (p-trend = 0.152). Frequent stair climbing was associated with lower ASCVD incidence; however, this association was partly explained by lifestyle and clinical factors of participants.

Abstract 10288: Lipoprotein(a) and Long-Term Risk of Atherosclerotic Cardiovascular Disease in a US Pooled Cohort

Background: Lipoprotein(a) [Lp(a)] is a common genetic factor associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large prospective primary prevention cohorts of the US population, including those with diabetes. Methods: We examined the relation of Lp(a) with ASCVD outcomes in a pooled cohort of five major US prospective studies: the Multiethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, Jackson, Framingham Offspring, and Atherosclerosis Risk in Communities. Lp(a) levels were examined continuously (per 50 mg/dL) and categorically as follows: &lt;15 mg/dL (reference), 15-29 mg/dL, 30-49 mg/dL, 50-69 mg/dL, and &gt; 70 mg/dL. Cox regression, adjusted for age, sex, race/ethnicity, LDL-C, and other risk factors, examined the relation of Lp(a) levels with total incident ASCVD events (non-fatal and fatal myocardial infarction, stroke, revascularization, and coronary heart disease death) in the pooled cohort overall and among those at low-intermediate (&lt;20%) and high ( &gt; 20%) 10-year risk and in those with diabetes. Results: We included 27,756 persons without prior ASCVD (mean age 51.3 + 12.4 years, 55.0% female, and 35.7% black participants) who had a mean follow-up of 21.1 + 9.9 years for ASCVD events. The table below shows the adjusted hazard ratios (HRs) and 95% confidence intervals for Lp(a) levels in relation to ASCVD events. In the overall sample, a 50 mg/dL increment in Lp(a) was associated with a 26% greater risk and compared to &lt;15 mg/dL those with Lp(a) levels of 15-29 mg/dL, 30-40 mg/dL, 50-69 mg/dL, and &gt; 70 mg/dL had 10%, 31%, 44%, and 30% greater risks of ASCVD events. Relationships were stronger in those with diabetes. Conclusions: Our results demonstrate in a large pooled cohort of US prospective studies relationships of increased ASCVD risk begin above Lp(a) levels of 15 mg/dL, especially in those with diabetes.