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Predictors of Coronary Artery Calcium and Long-Term Risks of Death, Myocardial Infarction, and Stroke in Young Adults.

ABSTRACT: Background Coronary artery calcium (CAC) is well-validated for cardiovascular disease risk stratification in middle to older-aged adults; however, the 2019 American College of Cardiology/American Heart Association guidelines state that more data are needed regarding the performance of CAC in low-risk younger adults. Methods and Results We measured CAC in 13 397 patients aged 30 to 49 years without known cardiovascular disease or malignancy between 1997 and 2009. Outcomes of myocardial infarction (MI), stroke, major adverse cardiovascular events (MACE; MI, stroke, or cardiovascular death), and all-cause mortality were assessed using Cox proportional hazard models, controlling for baseline risk factors (including atrial fibrillation for stroke and MACE) and the competing risk of death or noncardiac death as appropriate. The cohort (74% men, mean age 44 years, and 76% with ≤1 cardiovascular disease risk factor) had a 20.6% prevalence of any CAC. CAC was independently predicted by age, male sex, White race, and cardiovascular disease risk factors. Over a mean of 11 years of follow-up, the relative adjusted subhazard ratio of CAC >0 was 2.9 for MI and 1.6 for MACE. CAC >100 was associated with significantly increased hazards of MI (adjusted subhazard ratio, 5.2), MACE (adjusted subhazard ratio, 3.1), stroke (adjusted subhazard ratio, 1.7), and all-cause mortality (hazard ratio, 2.1). CAC significantly improved the prognostic accuracy of risk factors for MACE, MI, and all-cause mortality by the likelihood ratio test (P<0.05). Conclusions CAC was prevalent in a large sample of low-risk young adults. Those with any CAC had significantly higher long-term hazards of MACE and MI, while severe CAC increased hazards for all outcomes including death. CAC may have utility for clinical decision-making among select young adults.

SUBMITTER: Javaid A

PROVIDER: S-EPMC8751911 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceSerum calcium has been associated with cardiovascular disease in observational studies and evidence from randomized clinical trials indicates that calcium supplementation, which raises serum calcium levels, may increase the risk of cardiovascular events, particularly myocardial infarction.ObjectiveTo evaluate the potential causal association between genetic variants related to elevated serum calcium levels and risk of coronary artery disease (CAD) and myocardial infarction using mendelian randomization.Design, setting, and participantsThe analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs) identified from a genome-wide association meta-analysis of serum calcium levels (N = up to 61 079 individuals) and from the Coronary Artery Disease Genome-wide Replication and Meta-analysis Plus the Coronary Artery Disease Genetics (CardiogramplusC4D) consortium's 1000 genomes-based genome-wide association meta-analysis (N = up to 184 305 individuals) that included cases (individuals with CAD and myocardial infarction) and noncases, with baseline data collected from 1948 and populations derived from across the globe. The association of each SNP with CAD and myocardial infarction was weighted by its association with serum calcium, and estimates were combined using an inverse-variance weighted meta-analysis.ExposuresGenetic risk score based on genetic variants related to elevated serum calcium levels.Main outcomes and measuresCo-primary outcomes were the odds of CAD and myocardial infarction.ResultsAmong the mendelian randomized analytic sample of 184 305 individuals (60 801 CAD cases [approximately 70% with myocardial infarction] and 123 504 noncases), the 6 SNPs related to serum calcium levels and without pleiotropic associations with potential confounders were estimated to explain about 0.8% of the variation in serum calcium levels. In the inverse-variance weighted meta-analysis (combining the estimates of the 6 SNPs), the odds ratios per 0.5-mg/dL increase (about 1 SD) in genetically predicted serum calcium levels were 1.25 (95% CI, 1.08-1.45; P = .003) for CAD and 1.24 (95% CI, 1.05-1.46; P = .009) for myocardial infarction.Conclusions and relevanceA genetic predisposition to higher serum calcium levels was associated with increased risk of CAD and myocardial infarction. Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown.

Project description:Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD).To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort.Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded.Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ?1 stenosis ?20% but no stenosis ?70%; obstructive CAD: any stenosis ?70% or left main [LM] stenosis ?50%) and distribution (1, 2, or 3 vessel).The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality.Among 37,674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20,899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n?=?8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n?=?10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56% (n?=?13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n?=?6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18% (n?=?101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n?=?110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n?=?137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1- or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome.In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients.

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Predictors of Coronary Artery Calcium and Long-Term Risks of Death, Myocardial Infarction, and Stroke in Young Adults.

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