Key result
Homozygous chr7:111,666,943 T allele linked to ~80% higher risk of adverse cardiovascular events.
Why the study?
Excessive microvascular constriction during mental stress predicts adverse outcomes, but whether genetic factors contribute to this response in coronary artery disease was unknown.
Does the chr7:111,666,943 T allele or lower sPAT-ratio predict recurrent cardiovascular events in patients with coronary artery disease?
Cohort (n=580)
Yes
Does the chr7:111,666,943 T allele or lower sPAT-ratio predict recurrent cardiovascular events in patients with coronary artery disease?
A novel genetic locus on chromosome 7 modulates stress-induced microvascular constriction, which is associated with an increased risk of recurrent cardiovascular events in patients with CAD.
May inform CAD risk models with genetic microvascular markers; leaves open validation before clinical adoption.
Excessive peripheral microvascular constriction during acute psychological stress reflects similar changes in coronary blood flow and is a predictor of adverse cardiovascular outcomes. Among individuals with coronary artery disease (CAD), we sought to determine if genetic factors contribute to the degree of microvascular constriction during mental stress. A total of 580 stable CAD individuals from two prospective cohort studies underwent mental stress testing. Digital pulse wave amplitude was continuously measured and the stress/rest (sPAT) ratio of pulse wave amplitude was calculated. Race stratified genome-wide association studies (GWAS) of sPAT-ratio were conducted using linear regression of additive genetic models. A trans-ethnic meta-analysis integrated the four sets of GWAS results. Participants were followed for the outcome of recurrent cardiovascular events (myocardial infarction, heart failure, revascularization, and CV death) for a median of 5 years. We used Wei-Lin-Weissfeld (WLW) model to assess the association between sPAT-ratio with recurrent events. Mean age was 63 ± 9. We identified three SNPs in linkage disequilibrium, closely related to chr7:111,666,943 T > C (rs6466396) that were associated with sPAT-ratio (p = 6.68E-09). Participants homozygous for the T allele had 80% higher risk of incident adverse events (HR 1.8, 95% CI, 1.4-2.2). Also, participants with a lower sPAT-ratio (< median) had a higher adverse event rate, hazard ratio (HR) = 1.3, [95%confidence interval (CI), 1.1-1.6]. However, adjustment for the genotypes did not substantially alter the impact of sPAT ratio on adverse outcome rate. In conclusion, we have identified a genetic basis for stress-induced vasomotion. The 3 linked variants modulate vasoconstriction during mental stress may have a prognostic importance.
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Almuwaqqat et al. (2024) conducted a cohort in Coronary artery disease (CAD) (n=580). Homozygous T allele at chr7:111,666,943 (rs6466396) vs. Non-homozygous T allele was evaluated on Recurrent cardiovascular events (myocardial infarction, heart failure, revascularization, and CV death) (HR 1.8, 95% CI 1.4-2.2). Participants homozygous for the T allele at the chr7:111,666,943 locus had an 80% higher risk of incident adverse cardiovascular events (HR 1.8) compared to those without the risk allele.
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