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Coronary artery calcium (CAC) scoring is a powerful tool for atherosclerotic cardiovascular disease risk stratification. The nongated, noncontrast chest computed tomography scan (NCCT) has emerged as a source of CAC characterization with tremendous potential due to the high volume of NCCT scans. Application of incidental CAC characterization from NCCT has raised questions around score accuracy, standardization of methodology including the possibility of deep learning to automate the process, and the risk stratification potential of an NCCT-derived score. In this review, the authors aim to summarize the role of NCCT-derived CAC in preventive cardiovascular health today as well as explore future avenues for eventual clinical applicability in specific patient populations and broader health systems., Competing Interests: Funding Support and Author Disclosures Dr Joshi has received grant support from Novartis, Novo Nordisk, Kaneka, and Amgen; has received consulting fees from Novartis; and has received equity in G3 Therapeutics. Dr Rao has received grant support from Quest; and has received consulting fees from CSL, Raydel, Johnson and Johnson, JP Morgan, and Quest. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Identifying the association of novel plasma biomarkers with coronary artery calcium (CAC) incidence or progression may provide insights into the pathophysiology of atherogenesis and plaque formation., Methods: Participants of the Dallas Heart Study (DHS), a multi-ethnic cohort of ambulatory individuals at low-intermediate risk for future atherosclerotic cardiovascular disease (ASCVD), who had their blood tested for 31 biomarkers reflecting multiple pathophysiological pathways, underwent 2 serial non-contrast computed tomography assessments for CAC a median ∼7 years apart. The collected biomarkers were explored for association with CAC incidence or progression using univariate and multivariate analysis., Results: A total of 1424 participants were included; mean age 43 years, 39 % male, and nearly half African-American. Over a 7-year interval between the two CAC measurements, 340 participants (23.9 %) had CAC incidence or progression, 105 (7.4 %) with incident CAC, and 309 (21.7 %) with CAC progression. Although several plasma biomarkers were associated with CAC incidence or progression in a univariate model, only soluble intercellular adhesion molecule-1 (sICAM-1), related to atherosclerosis by the inflammatory pathway, remained independently associated in a multivariate model adjusted for traditional risk factors., Conclusions: Further studies are needed to characterize the role of sICAM-1 in CAC evolvement to establish whether it has a pivotal mechanistic contribution or is rather an innocent bystander. Alternate measures of coronary atherosclerosis may be needed to elucidate contributors to atherosclerosis incidence or progression., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Neeland has been a speaker/consultant for Boehringer-Ingelheim/Lilly Alliance and Bayer Pharmaceuticals and has been an advisory board member for AMRA Medical, Boehringer Ingelheim, Bayer, and Lilly. Dr. Eisen has been a speaker/consultant/ Advisory board member for Boehringer-Ingelheim, Bayer, Novo Nordisk, AstraZeneca, Pfizer, Neopharm, Medison Pharma, and Sanofi. Dr. de Lemos reports grant support from Roche Diagnostics and Abbott Diagnostics, consulting fees from Quidel Cardiovascular, Inc., Cytokinetics and Glaxo Smith Kline, honoraria for participation in endpoint committees from Beckman Coulter and Siemens Health Care Diagnostics, and fees for participation in Data Monitoring Committees from Astra Zeneca, Novo Nordisk, Eli Lilly, Regeneron, Amgen, and Verve Therapeutics., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Higher rates of dementia are reported in people with a history of coronary artery disease. Smaller hippocampal volume (HV) is a risk factor for the development of dementia., Objective: This study assessed whether coronary artery calcification (CAC) and carotid intima media thickness (CIMT) are associated with HV in participants from the Dallas Heart Study, a community-based study of Dallas County, Texas, residents., Methods: Data from a total of n = 1821 participants in the Dallas Heart Study with brain magnetic resonance imaging, CAC, and CIMT information were included in the present study, after excluding those with a history of myocardial infarction or stroke. To evaluate the effect of CAC and CIMT on total HV, 4 linear regression analyses were conducted in which the primary predictor was (1) CAC as a continuous metric; (2) CAC as a binary metric (CAC = 0 vs. CAC ≥ 1); (3) CAC as a continuous metric but only for those with CAC >0; and (4) CIMT as a continuous metric. Demographic and cardiovascular disease risk factors, as well as intracranial volume, were entered into the model as covariates., Results: Participants were largely women (58.2%) with a mean age of 49.7 ± 10.3 years. Forty-six percent of the sample reported being Black, and approximately 14% reported being Hispanic. All 3 variations of the CAC effect were nonsignificant predictors of total HV (β = -0.013, P = 0.602; β = -0.011, P = 0.650; β = 0.036, P = 0.354, respectively), as was the effect of CIMT (β = 0.009, P = 0.686)., Conclusions: Current findings suggest nonsignificant relationships between both CAC and CIMT and between CAC and total HV, while controlling for other related factors in a large, diverse, community-based sample of people without a history of myocardial infarction or stroke. In the context of existing evidence that both coronary artery disease and smaller HV are associated with the development of dementia, the present findings suggest that neither marker of the cardiovascular disease examined here is associated with a reduction in HV in the population studied. Longitudinal studies are needed to assess relationships between CAC and CIMT and between CAC and HV over time., (Copyright © 2023 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Soluble Fms-like tyrosine kinase-1 (sFlt-1) plays a role in angiogenesis, atherogenesis, and preeclampsia. The relationship of sFlt-1 with markers of subclinical atherosclerosis and future atherosclerotic cardiovascular disease (ASCVD) events in a generally healthy population is unknown., Methods: Participants in the Dallas Heart Study with sFlt-1 measured were included (n = 3292). Abdominal aortic atherosclerosis was measured by MRI and coronary artery calcium (CAC) by CT. The cohort was also followed for subsequent ASCVD events (CV death, MI, stroke, unstable angina, revascularization). Multivariable linear and logistic regression analyses and Cox regression analyses were performed adjusting for demographics and traditional cardiac risk factors., Results: sFlt-1 levels were higher in older individuals, males, and African Americans, and tracked with most traditional risk factors. sFlt-1 was significantly associated with higher prevalence of aortic plaque [OR 1.33 (95% CI 1.02-1.73)], greater abdominal aortic wall thickness (p<0.01) and aortic plaque area (p<0.02) but no difference in coronary artery calcification. There were 322 ASCVD events over 12 years of follow-up. Higher sFlt-1 levels associated with increased ASCVD events in unadjusted (16.1% vs. 8.9%, p<0.001, quartile 4 vs. quartile 1) and adjusted analyses (HR 1.58 [1.14-2.18], p<0.01, quartile 4 vs. quartile 1). Findings were unchanged when analyzing sFlt-1 as a continuous variable or when excluding those with a history of ASCVD., Conclusions: In a population-based cohort, sFlt-1 is associated with measures of subclinical aortic atherosclerosis and clinical ASCVD events. Future studies are warranted on the therapeutic potential of targeting sFlt-1 for atherosclerotic disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Importance: Higher coronary artery calcium (CAC) identifies individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether it can also identify individuals likely to derive net benefit from aspirin therapy is unclear., Objective: To examine the association between CAC, bleeding, and ASCVD and explore the net estimated effect of aspirin at different CAC thresholds., Design, Setting, and Participants: Prospective population-based cohort study of Dallas Heart Study participants, free from ASCVD and not taking aspirin at baseline. Data were analyzed between February 1, 2020, and July 15, 2020., Exposures: Coronary artery calcium score in the following categories: 0, 1-99, and 100 or higher., Main Outcomes and Measures: Major bleeding and ASCVD events were identified from International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. Meta-analysis-derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds., Results: A total of 2191 participants (mean [SD], age 44 [9.1] years, 1247 women [57%], and 1039 black individuals [47%]) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC 1-99 and ≥100 vs CAC 0) were associated with both ASCVD and bleeding events (hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3; HR, 4.8; 95% CI, 2.8-8.2; P < .001; HR, 5.3; 95% CI, 3.6-7.9; P < .001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (<5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (≥20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of at least 100 identified individuals who would experience net benefit, but only in those at borderline or higher (≥5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk., Conclusions and Relevance: Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.

Background: High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C., Methods: We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA (Multi-Ethnic Study of Atherosclerosis; n=6632), and PREVEND (Prevention of Renal and Vascular Endstage Disease; n=5022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke., Results: In the overall population (n=15 784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors (hazard ratio [HR] for quartile 4 [Q4] versus quartile 1 [Q1], 0.64 [95% CI, 0.52-0.78]), as was HDL-C (HR for Q4 versus Q1, 0.76 [95% CI, 0.61-0.94]). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and atherosclerotic cardiovascular disease, whereas adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual end points of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR for Q4 versus Q1 for Whites, 0.49 [95% CI, 0.35-0.69]; for Blacks, 1.22 [95% CI, 0.76-1.98]; P interaction =0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR for Q4 versus Q1, 0.53 [95% CI, 0.36-0.78]) but had a weak direct association with MI among Black participants (HR for Q4 versus Q1, 1.75 [95% CI, 1.08-2.83]; P interaction <0.0001)., Conclusions: Compared with HDL-C, HDL-P was consistently associated with MI and ischemic stroke in the overall population. Differential associations of both HDL-C and HDL-P for MI by Black ethnicity suggest that atherosclerotic cardiovascular disease risk may differ by vascular domain and ethnicity. Future studies should examine individual outcomes separately.

Objectives: This study sought to assess the effect of coronary artery calcium (CAC) on coronary heart disease (CHD) risk prediction in a younger population., Background: CAC measured by computed tomography improves CHD risk classification in older adults, but the effectiveness of CAC in younger populations has not been fully assessed., Methods: In the DHS (Dallas Heart Study), a multiethnic probability-based population sample, traditional CHD risk factors and CAC were measured in participants without baseline cardiovascular disease or diabetes. Incident CHD-defined as CHD death, myocardial infarction, or coronary revascularization-was assessed over a median follow-up of 9.2 years. Predicted CHD risk was assessed with a Weibull model inclusive of traditional risk factors before and after the addition of CAC as ln(CAC + 1). Participants were divided into 3 10-year risk categories, <6%, 6% to <20%, and ≥20%, and the net reclassification improvement (NRI) was calculated. We also performed a random-effects meta-analysis of NRI from previous studies inclusive of older individuals., Results: The analysis comprised 2,084 participants; mean age was 44.4 ± 9.0 years. CAC was independently associated with incident CHD (hazard ratio per SD: 1.90, 95% confidence interval [CI] 1.51 to 2.38; p < 0.001). The addition of CAC to the traditional risk factor model resulted in significant improvement in the C-statistic (delta = 0.03; p = 0.003). Among participants with CHD events, the addition of CAC resulted in net correct upward reclassification of 21%, and among those without CHD, a net correct downward reclassification of 0.5% (NRI: 0.216, p = 0.012). Results remained significant when the outcome was restricted to CHD death and myocardial infarction and when individuals with diabetes were included. The NRI observed in this study was similar to the pooled estimate from previous studies (0.200, 95% CI: 0.140 to 0.258) and the addition of our study to the meta-analysis did not result in significant heterogeneity (I(2) = 0%)., Conclusions: CAC scoring also improves CHD risk classification in younger adults., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Therapies targeting high-density lipoprotein cholesterol content (HDL-C) have not improved coronary heart disease (CHD) outcomes. High-density lipoprotein particle concentration (HDL-P) may better predict CHD. However, the impact of race/ethnicity on the relations between HDL-P and subclinical atherosclerosis and incident CHD events has not been described. Participants from the Dallas Heart Study (DHS), a multiethnic, probability-based, population cohort of Dallas County adults, underwent the following baseline measurements: HDL-C, HDL-P by nuclear magnetic resonance imaging, and coronary artery calcium by electron-beam computed tomography. Participants were followed for a median of 9.3 years for incident CHD events (composite of first myocardial infarction, stroke, coronary revascularization, or cardiovascular death). The study comprised 1,977 participants free of CHD (51% women, 46% black). In adjusted models, HDL-C was not associated with prevalent coronary artery calcium (p = 0.13) or incident CHD overall (hazard ratio [HR] per 1 SD 0.89, 95% confidence interval [CI] 0.76 to 1.05). However, HDL-C was inversely associated with incident CHD among nonblack (adjusted HR per 1 SD 0.67, 95% CI 0.46 to 0.97) but not black participants (HR 0.94, 95% CI 0.78 to 1.13, pinteraction = 0.05). Conversely, HDL-P, adjusted for risk factors and HDL-C, was inversely associated with prevalent coronary artery calcium (p = 0.009) and with incident CHD overall (adjusted HR per 1 SD 0.73, 95% CI 0.62 to 0.86), with no interaction by black race/ethnicity (pinteraction = 0.57). In conclusion, in contrast to HDL-C, the inverse relation between HDL-P and incident CHD events is consistent across ethnicities. These findings suggest that HDL-P is superior to HDL-C in predicting prevalent atherosclerosis as well as incident CHD events across a diverse population and should be considered as a therapeutic target., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The absence of coronary artery calcium (CAC) in middle age is associated with very low short-term risk for coronary events. However, the long-term implications of a CAC score of 0 are uncertain, particularly among individuals with high cardiovascular lifetime risk. We sought to characterize the association between predicted lifetime risk and incident CAC among individuals with low short-term risk., Methods and Results: We included 754 Dallas Heart Study participants with serial CAC scans (6.9 years apart) and both low short-term risk and baseline CAC=0. Lifetime risk for cardiovascular disease was estimated according to risk factor burden. Among this group, 365 individuals (48.4%) were at low lifetime risk and 389 (51.6%) at high lifetime risk. High lifetime risk was associated with higher annualized CAC incidence (4.2% versus 2.7%; P < 0.001). Similarly, mean follow-up CAC scores were higher among participants with high lifetime risk (7.8 versus 2.4 Agatston units). After adjustment for age, sex, and race, high lifetime risk remained independently associated with incident CAC (OR 1.60; 95% CI 1.12 to 2.27; P=0.01). When assessing risk factor burden at the follow-up visit, 66.7% of CAC incidence observed in the low lifetime risk group occurred among individuals reclassified to a higher short- or long-term risk category., Conclusion: Among individuals with low short-term risk and CAC scores of 0, high lifetime risk is associated with a higher incidence of CAC. These findings highlight the importance of lifetime risk even among individuals with very low short-term risk., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Growth differentiation factor 15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions. Although higher circulating GDF-15 concentrations are associated with mortality across a spectrum of cardiovascular conditions, the relationship of GDF-15 with atherosclerosis and mortality in the general population remains undefined., Methods: We measured plasma GDF-15 in 3219 participants of the Dallas Heart Study, a population sample of adults ages 30-65 years (55% women, 49% black). GDF-15 was analyzed in prespecified categories (<1200; 1200-1799; and ≥1800 ng/L) and continuously. End points included prevalent coronary artery calcium (CAC>10 Agatston units), increased CAC (CAC≥100 Agatston units) by electron beam computed tomography, and mortality through a median 7.3 years of follow-up (120 deaths, 48 cardiovascular deaths)., Results: Increasing GDF-15 associated with older age, black race, hypertension, diabetes, smoking, left ventricular (LV) mass/body surface area, and worse renal function (P<0.0001 for each). In multivariable models adjusted for traditional risk factors, renal function, and LV mass/body surface area, GDF-15≥1800 ng/L was associated with CAC>10 (odds ratio 2.1; 95% CI 1.2-3.7; P=0.01), CAC≥100 (odds ratio 2.6; 95% CI 1.4-4.9; P=0.002), all-cause mortality (hazard ratio 3.5; 95% CI 2.1-5.9, P<0.0001), and cardiovascular mortality (hazard ratio 2.5; 95% CI 1.1-5.8, P=0.03). Adding log GDF-15 to fully adjusted models modestly improved the c statistic (P=0.025), the integrated discrimination index (0.028; P<0.0001) and the category-less net reclassification index (0.42; P=0.002). These findings remained significant with further adjustment for high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T., Conclusions: GDF-15 is independently associated with subclinical coronary atherosclerosis and mortality, and its potential role for risk stratification in the general population merits further evaluation.

Objective: Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population., Methods and Results: Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08-1.84), APB (beta coefficient 0.23, p = 0.02), and AWT (beta coefficient 0.04, p = 0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61-1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (p(interaction) = 0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23-2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68-1.44)., Conclusion: Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Previous studies have derived and validated an HDL apolipoproteomic score (pCAD) that predicts coronary artery disease (CAD) risk. However, the associations between pCAD and markers of cardiometabolic health in healthy adults are not known, nor are the effects of regular exercise on pCAD. A total of 641 physically inactive adults free of cardiovascular disease from the HERITAGE Family Study completed 20 weeks of exercise training. The pCAD index (range 0–100) was calculated using measurements of apolipoproteins A-I, C–I, C-II, C-III, and C-IV from ApoA-I-tagged serum (higher index = higher CAD risk). The associations between pCAD index and cardiometabolic traits at baseline and their training responses were assessed with Spearman correlation and general linear models. A Bonferroni correction of p < 8.9 × 10−04 was used to determine statistical significance. The mean ± SD baseline pCAD index was 29 ± 32, with 106 (16.5 %) participants classified as high CAD risk. At baseline, pCAD index was positively associated with blood pressure, systemic inflammation, and body composition. HDL size, VO 2 max, and HDL-C were negatively associated with pCAD index at baseline. Of those classified as high CAD risk at baseline, 52 (49 %) were reclassified as normal risk after training. Following training, pCAD index changes were inversely correlated (p < 1.4 × 10−04) with changes in HDL-C, HDL size, and LDL size. A higher pCAD index was associated with a worse cardiometabolic profile at baseline but improved with regular exercise. The results from this study highlight the potential role of HDL apolipoproteins as therapeutic targets for lifestyle interventions, particularly in high-risk individuals. [Display omitted] • A higher HDL apolipoproteomic index (pCAD) was associated with a worse cardiometabolic profile at baseline. • Individuals with the highest pCAD had the greatest reductions in pCAD following regular exercise. • HDL apolipoproteins are potential therapeutic targets for lifestyle interventions. [ABSTRACT FROM AUTHOR]

Introduction: Elevated lipoprotein(a) [Lp(a)] levels and family history of coronary heart disease (FHx) are associated with an increased risk of cardiovascular events. Whether elevated Lp(a) and FHx have an additive association with long-term atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) risk is unclear. Hypothesis: High Lp(a) and FHx have an additive joint association with long-term ASCVD and CHD risk. Methods: ARIC study participants free of ASCVD had Lp(a) measured using a sandwich ELISA and were followed for clinical events. The independent and joint associations of FHx at any age and race-specific Lp(a) quintiles with ASCVD (CV death, non-fatal MI, non-fatal stroke) and CHD (CHD death, non-fatal MI) were assessed using cumulative incidence curves and Cox proportional hazards models adjusted for ACC/AHA pooled cohort equation risk factors (age, gender, race, diabetes, smoking, systolic BP, antihypertensive use, total cholesterol, HDL cholesterol) and statin use. Results: Among 12,149 participants (56% female, 23% blacks, mean age 54 years), 44% had FHx and after a mean follow-up of 21 years, 3,114 ASCVD and 2,283 CHD events were observed. High race-specific Lp(a) level (quintile 5 vs. quintile 1) and FHx were independently associated with ASCVD [HR (95% CI), 1.25 (1.19-1.40) and 1.17 (1.09-1.26); respectively] and CHD events [HR 1.27 (1.12-1.45) and 1.31 (1.12-1.42); respectively] in adjusted models. Presence of FHx and high Lp(a) (quintile 5) had an additive association with long-term ASCVD and CHD risk (Figure). Compared to those without FHx and lower Lp(a) (quintile 1-4), those with either high Lp(a) or FHx had a higher adjusted hazard of ASCVD and CHD (p<0.05 each), while those with both had the highest risk [HR 1.43 (1.27-1.62) and 1.68 (1.47-1.93) for CHD and ASCVD, respectively]. Similar results were observed in analyses stratified by FHx of premature CHD (CHD in father before age 55 years or mother before age 60 years). Conclusion: In this large biracial population-based cohort of individuals free of CVD, we observed an independent and additive joint association of high Lp(a) and FHx with long-term ASCVD as well as CHD risk. [ABSTRACT FROM AUTHOR]