Insulin resistance genetic risk score and burden of coronary artery disease in patients referred for coronary angiography

AimsInsulin resistance associates with development of metabolic syndrome and risk of cardiovascular disease. The link between insulin resistance and cardiovascular disease is complex and multifactorial. Confirming the genetic link between insulin resistance, type 2 diabetes, and coronary artery disease, as well as the extent of coronary artery disease, is important and may provide better risk stratification for patients at risk. We investigated whether a genetic risk score of 53 single nucleotide polymorphisms known to be associated with insulin resistance phenotypes was associated with diabetes and burden of coronary artery disease.Methods and resultsWe genotyped patients with a coronary angiography performed in the capital region of Denmark from 2010-2014 and constructed a genetic risk score of the 53 single nucleotide polymorphisms. Logistic regression using quartiles of the genetic risk score was performed to determine associations with diabetes and coronary artery disease. Associations with the extent of coronary artery disease, defined as one-, two- or three-vessel coronary artery disease, was determined by multinomial logistic regression. We identified 4,963 patients, of which 17% had diabetes and 55% had significant coronary artery disease. Of the latter, 27%, 14% and 14% had one, two or three-vessel coronary artery disease, respectively. No significant increased risk of diabetes was identified comparing the highest genetic risk score quartile with the lowest. An increased risk of coronary artery disease was found for patients with the highest genetic risk score quartile in both unadjusted and adjusted analyses, OR 1.21 (95% CI: 1.03, 1.42, p = 0.02) and 1.25 (95% CI 1.06, 1.48, pConclusionsAmong patients referred for coronary angiography, only a strong genetic predisposition to insulin resistance was associated with risk of coronary artery disease and with a greater disease burden

Association of genetic variants previously implicated in coronary artery disease with age at onset of coronary artery disease requiring revascularizations

BACKGROUND:The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography. METHODS:1599 individuals (mean age 64 years [min-max 29-96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010-2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies. RESULTS:Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CAD-GRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively. CONCLUSIONS:Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a "missing heritability" in early-onset CAD warrants more research

Short-term mortality risk of serum potassium levels in acute heart failure following myocardial infarction

AIMS: Diuretic treatment is often needed in acute heart failure following myocardial infarction (MI) and carries a risk of abnormal potassium levels. We examined the relation between different levels of potassium and mortality. METHODS AND RESULTS: From Danish national registries we identified 2596 patients treated with loop diuretics after their first MI episode where potassium measurement was available within 3 months. All-cause mortality was examined according to seven predefined potassium levels: hypokalaemia <3.5 mmol/L, low normal potassium 3.5–3.8 mmol/L, normal potassium 3.9–4.2 mmol/L, normal potassium 4.3–4.5 mmol/L, high normal potassium 4.6–5.0 mmol/L, mild hyperkalaemia 5.1–5.5 mmol/L, and severe hyperkalaemia: >5.5 mmol/L. Follow-up was 90 days and using normal potassium 3.9–4.2 mmol/L as a reference, we estimated the risk of death with a multivariable-adjusted Cox proportional hazard model. After 90 days, the mortality rates in the seven potassium intervals were 15.7, 13.6, 7.3, 8.1, 10.6, 15.5, and 38.3%, respectively. Multivariable-adjusted risk for death was statistically significant for patients with hypokalaemia [hazard ratio (HR): 1.91, confidence interval (95%CI): 1.14–3.19], and mild and severe hyperkalaemia (HR: 2, CI: 1.25–3.18 and HR: 5.6, CI: 3.38–9.29, respectively). Low and high normal potassium were also associated with increased mortality (HR: 1.84, CI: 1.23–2.76 and HR: 1.55, CI: 1.09–2.22, respectively). CONCLUSION: Potassium levels outside the interval 3.9–4.5 mmol/L were associated with a substantial risk of death in patients requiring diuretic treatment after an MI