Naderian, Mohammadreza

BACKGROUND: In the Myocardial Infarction Genes clinical trial (URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01936675), participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (Framingham risk score group, n=103) or an integrated risk score (integrated risk score group [IRS g ], n=104) that additionally included a polygenic risk score. After 6 months, IRS g participants had higher statin initiation and lower low-density lipoprotein cholesterol. We conducted a post hoc 10-year follow-up analysis to investigate whether disclosure of a polygenic risk score for CHD was associated with a reduction in major adverse cardiovascular events (MACE). METHODS: Participants were followed from randomization in October 2013 to September 2023 to ascertain MACE, testing for CHD, and changes in risk factors. The primary outcome was time to first MACE, defined as cardiovascular death, nonfatal myocardial infarction, coronary revascularization, and nonfatal stroke. Statistical analyses included Cox proportional hazards regression and linear mixed-effects models. RESULTS: We followed all participants who completed the trial, 100 in Framingham risk score group and 103 in IRS g (mean age at the end of follow-up, 68.2±5.2; 48% male). During a median follow-up of 9.5 years, 9 MACEs occurred in Framingham risk score group and 2 in IRS g (hazard ratio, 0.20 [95% CI, 0.04–0.94]; P =0.042). In Framingham risk score group, 47 (47%) underwent at least 1 diagnostic test for CHD, compared with 30 (29%) in IRS g (hazard ratio, 0.51 [95% CI, 0.32–0.81]; P =0.004). A higher proportion of IRS g participants were on statin therapy during the first 4 years postrandomization and had a greater reduction in low-density lipoprotein cholesterol for up to 3 years postrandomization. No significant differences were observed between 2 groups in other traditional cardiovascular risk factors during follow-up. CONCLUSIONS: Disclosure of an integrated risk score that included a polygenic risk score to individuals at intermediate risk for CHD was associated with lower MACE incidence after 10 years, likely due to higher statin initiation, leading to lower low-density lipoprotein cholesterol levels.

BACKGROUND: Coronary atherosclerotic burden and adverse coronary heart disease events are related phenotypes with likely shared genetic cause. METHODS: We analyzed 6021 patients with available coronary angiography, genotyping, and exome sequencing data. We tested for associations of polygenic risk scores for coronary heart disease (PRS CHD ) with multiple measures of coronary artery disease (CAD) severity. We assessed the joint associations of PRS CHD and pathogenic/likely pathogenic variants in 3 familial hypercholesterolemia genes, with CAD severity. We performed mediation analyses to explore whether CAD severity mediated the association of PRS CHD with prevalent coronary heart disease and incident myocardial infarction. RESULTS: A 1-SD increase in PRS CHD was associated with multiple measures of CAD severity, including the log Gensini score (β, 0.31 [95% CI, 0.28–0.33]). Carrying a pathogenic/likely pathogenic familial hypercholesterolemia variant was associated with a higher log Gensini score after adjustment for PRS CHD (β, 0.21 [95% CI, 0.03–0.38]). A 1-SD increase in PRS CHD was associated with incident myocardial infarction over a mean follow-up of 9.2 years (hazard ratio, 1.20 [95% CI, 1.13–1.27]; P =5×10 − 10 ), and the Gensini score mediated 90% of this association. CONCLUSIONS: PRS CHD was associated with multiple measures of CAD severity. The association of PRS CHD with incident myocardial infarction was almost fully mediated by CAD severity, indicating a considerable genetic overlap between the 2 phenotypes.

Background The North Africa and Middle East (NAME) region has one of the highest burdens of ischemic heart disease (IHD) worldwide. This study reports the contemporary epidemiology of IHD in NAME. Methods and Results We estimated the incidence, prevalence, deaths, years of life lost, years lived with disability, disability‐adjusted life years (DALYs), and premature mortality of IHD, and its attributable risk factors in NAME from 1990 to 2019 using the results of the GBD (Global Burden of Disease study 2019). In 2019, 0.8 million lives and 18.0 million DALYs were lost due to IHD in NAME. From 1990 to 2019, the age‐standardized DALY rate of IHD significantly decreased by 33.3%, mostly due to the reduction of years of life lost rather than years lived with disability. In 2019, the proportion of premature death attributable to IHD was higher in NAME compared with global measures: 26.8% versus 16.9% for women and 18.4% versus 14.8% for men, respectively. The age‐standardized DALY rate of IHD attributed to metabolic risks, behavioral risks, and environmental/occupational risks significantly decreased by 28.7%, 37.8%, and 36.4%, respectively. Dietary risk factors, high systolic blood pressure, and high low‐density lipoprotein cholesterol were the top 3 risks contributing to the IHD burden in most countries of NAME in 2019. Conclusions In 2019, IHD was the leading cause of death and lost DALYs in NAME, where premature death due to IHD was greater than the global average. Despite the great reduction in the age‐standardized DALYs of IHD in NAME from 1990 to 2019, this region still had the second‐highest burden of IHD in 2019 globally.

Background Particulate matter (PM) pollution is a significant risk factor for cardiovascular diseases, causing substantial disease burden and deaths worldwide. This study aimed to investigate the global burden of cardiovascular diseases attributed to PM from 1990 to 2019. Methods and Results We used the GBD (Global Burden of Disease) study 2019 to investigate disability‐adjusted life‐years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and deaths attributed to PM as well as its subgroups. It was shown that all burden measures' age‐standardized rates for PM were in the same decreasing trend, with the highest decline recorded for deaths (−36.7%). However, the all‐age DALYs increased by 31%, reaching 8.9 million in 2019, to which YLLs contributed the most (8.2 million [95% uncertainty interval, 7.3 million–9.2 million]). Men had higher deaths, DALYs, and YLLs despite lower years lived with disability in 2019 compared with women. There was an 8.1% increase in the age‐standardized rate of DALYs for ambient PM; however, household air pollution from solid fuels decreased by 65.4% in the assessed period. Although higher in men, the low and high sociodemographic index regions had the highest and lowest attributed YLLs/YLDs ratio for PM pollution in 2019, respectively. Conclusions Although the total age‐standardized rate of DALYs for PM‐attributed cardiovascular diseases diminished from 1990 to 2019, the global burden of PM on cardiovascular diseases has increased. The differences between men and women and between regions have clinical and policy implications in global health planning toward more exact funding and resource allocation, in addition to addressing inequity in health care access.