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Background: Childhood cancer survivors have increased risk of dyslipidemia and atherosclerotic cardiovascular disease (CVD). The aim of this study was to evaluate the prevalence and associated cardiovascular risks of specific lipid abnormalities among childhood cancer survivors., Methods: Comprehensive lipid panel measurements were obtained from 4115 5-year survivors, with 3406 (mean age at evaluation = 35.2 years, SD = 10.4 years) not having previous dyslipidemia diagnosis, as well as 624 age, sex, and race and ethnicity matched community controls., Results: Previously undiagnosed dyslipidemia with abnormal low-density lipoprotein (LDL) cholesterol (>160 mg/dL), non-high density lipoprotein (HDL) cholesterol (>190 mg/dL), HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women), and triglycerides (>150 mg/dL) were identified in 4%, 6%, 30%, and 17%, respectively. Survivors without previous dyslipidemia diagnosis had higher LDL cholesterol and non-HDL cholesterol and lower HDL cholesterol than community controls. Cranial radiotherapy (relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.6 to 3.0 for non-HDL cholesterol) and total body irradiation for hematopoietic cell transplantation (RR = 6.7, 95% CI = 3.5 to 13.0 for non-HDL cholesterol; RR = 9.9, 95% CI = 6.0 to 16.3 for triglycerides) were associated with greater risk of dyslipidemia. Diagnoses of low HDL cholesterol (hazard ratio [HR] = 2.9, 95% CI = 1.8 to 4.7) and elevated triglycerides (HR = 3.1, 95% CI = 1.9 to 5.1) were associated with increased risk for myocardial infarction, and diagnoses of high LDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), high non-HDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), low HDL cholesterol (HR = 3.9, 95% CI = 2.8 to 5.4), and elevated triglycerides (HR = 3.8, 95% CI = 2.7 to 5.5) were associated with increased risk for cardiomyopathy., Conclusions: Previously undiagnosed dyslipidemia among childhood cancer survivors was associated with increased risk for myocardial infarction and cardiomyopathy. Comprehensive dyslipidemia evaluation and treatment are needed to reduce cardiovascular morbidity in this population., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background High-density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size-based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size-based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. Methods and Results Seven HDL size-based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi-Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow-up (average 8-10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81-0.94]; H4 0.89 [95% CI, 0.82-0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88-0.99]; H4 0.91 [95% CI, 0.85-0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. Conclusions Two of 7 HDL size-based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.

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.)

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 aimed to investigate the independent and joint associations between family history of myocardial infarction (FH) and coronary artery calcification (CAC) with incident coronary heart disease (CHD)., Background: FH and CAC are associated with each other and with incident CHD. It is not known whether FH retains its predictive value after CAC results are accounted for., Methods: Among 2,390 participants without cardiovascular disease enrolled in the Dallas Heart Study, we assessed FH (myocardial infarction in a first-degree relative) and prevalent CAC by electron-beam computed tomography. The primary outcome, a composite of CHD-related death, myocardial infarction, and percutaneous or surgical coronary revascularization, was assessed over a mean follow-up of 8.0 ± 1.2 years. The individual and joint associations with the CHD composite outcome were determined for FH and CAC., Results: The mean age of the population was 44 ± 9 years; 32% had FH and 47% had a CAC score of 0. In multivariate models adjusted for traditional risk factors, FH was independently associated with CHD (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). Further adjustment for prevalent CAC did not diminish this association (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). FH and CAC were additive: CHD event rates in those with both FH and CAC were 8.8% vs. 3.3% in those with prevalent CAC alone (p < 0.001). CHD rates were 1.9% in those with FH alone compared with 0.4% in those with neither FH nor CAC (p < 0.017). Among subjects without CAC, FH characterized a group with a more unfavorable cardiometabolic profile., Conclusions: FH provided prognostic information that was independent of and additive to CAC. Among those with CAC, FH identified subjects at particularly high short-term risk, and, among those without it, selected a group with an adverse risk-factor profile., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin β receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP)., Methods: Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo., Results: Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin β receptor (1.7 vs 2.4 ng/mL, P = .002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P = .01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P = .02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P = .003) and hs-CRP (0.42 vs 0.31 ng/mL, P = .02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P = .046)., Conclusion: Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Although chronic lung disease (CLD) is common among patients with myocardial infarction (MI), little is known about the influence of CLD on patient management and outcomes following MI., Methods: Using the National Cardiovascular Data Registry's ACTION Registry-GWTG, demographics, clinical characteristics, treatments, processes of care, and in-hospital adverse events after acute MI were compared between patients with (n = 22,624) and without (n = 136,266) CLD. Multivariable adjustment was performed to determine the independent association of CLD with treatments and adverse events., Results: CLD (17.0% of non-ST-elevation MI [NSTEMI] and 10.1% of ST-elevation MI [STEMI] patients) was associated with older age, female sex, and a greater burden of comorbidities. Among NSTEMI patients, those with CLD were less likely to undergo cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft compared to those without; in contrast, no differences were seen in invasive therapies for STEMI patients with or without CLD. Multivariable-adjusted risk of major bleeding was significantly increased in CLD patients with NSTEMI (13.0% vs 8.1%, OR(adj) = 1.27, 95% CI = 1.20-1.34, P < .001) and STEMI (16.0% vs 10.5%, OR(adj) = 1.19, 95% CI = 1.10-1.29, P < .001). In NSTEMI, CLD was associated with a higher risk of inhospital mortality (OR(adj) = 1.21, 95% CI = 1.11-1.33); in STEMI no association between CLD and mortality was seen (OR(adj) = 1.05, 95% CI = 0.95-1.17)., Conclusions: CLD is common among patients with MI and is independently associated with an increased risk for major bleeding. In NSTEMI, CLD is also associated with receiving less revascularization and with increased in-hospital mortality. Special attention should be given to this high-risk subgroup for the prevention and management of complications after MI., (Copyright © 2013 Mosby, Inc. All rights reserved.)

A 40-year-old African-American woman presented with atypical chest pain, an acute non-ST segment elevation myocardial infarction, and angiographic evidence for severe ostial vasospasm of the left main and right coronary arteries. Subsequently, she was diagnosed with hyperthyroidism and treated with antithyroid therapy and oral nitrates. Repeat angiography revealed resolution of the vasospasm; however, the chest pain recurred in the euthyroid state. Hyperthyroidism-associated coronary vasospasm is a rare disorder that characteristically causes angina in young Asian women and resolves with correction of hyperthyroidism. We present an atypical case of an African-American woman presenting with a myocardial infarction who developed recurrent angina while euthyroid.

The authors consider the results of studies on the clinical utility of growth differentiation factor 15 (GDF-15) as biomarker for acute coronary syndromes (ACS) and chronic coronary artery disease (CAD). They cite the steps needed to determine the utility of a biomarker including the assessment of pre- and postanalytical factors which influence sample measurement. They mention the link between high GDF-15 levels and mortality based on the AtheroGene registry findings. They offer recommendation for future GDF-15 studies.

Background: Cholesterol efflux capacity (CEC), which is a key step in the reverse cholesterol transport pathway, is independently associated with atherosclerotic cardiovascular disease (ASCVD). However, whether it predicts ASCVD beyond validated novel risk markers is unknown.Objectives: This study assessed if CEC improved ACSVD risk prediction beyond using coronary artery calcium (CAC), family history (FH), and high-sensitivity C-reactive protein (hs-CRP).Methods: CEC, CAC, self-reported FH, and hs-CRP were assessed among participants without baseline ASCVD who were enrolled in the Dallas Heart Study (DHS). ASCVD was defined as a first nonfatal myocardial infarction (MI) or stroke, coronary revascularization, or cardiovascular death, assessed over a median 9.4 years. Risk prediction was assessed using various modeling techniques and improvements in the c-statistic, the integrated discrimination index (IDI), and the net reclassification index (NRI).Results: The mean age of the population (N = 1,972) was 45 years, 52% had CAC (>0), 31% had FH, and 58% had elevated hs-CRP (≥2 mg/l). CEC greater than the median was associated with a 50% reduced incidence of ASCVD in those with CAC (5.4% vs. 10.5%; p = 0.003), FH (5.8% vs. 10%; p = 0.05), and elevated hs-CRP (3.8% vs. 7.9%; p = 0.004). CEC improved all metrics of discrimination and reclassification when added to CAC (c-statistic, p = 0.004; IDI, p = 0.02; NRI: 0.38; 95% confidence interval [CI]: 0.13 to 0.53), FH (c-statistic, p = 0.006; IDI, p = 0.008; NRI: 0.38; 95% CI: 0.13 to 0.55), or elevated hs-CRP (c-statistic p = 0.008; IDI p = 0.02; NRI: 0.36; 95% CI 0.12 to 0.52).Conclusions: CEC improves ASCVD risk prediction beyond using CAC, FH, and hs-CRP and warrants consideration as a novel ASCVD risk marker. [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]