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The ENPP1 Q121 variant predicts major cardiovascular events in high-risk individuals: evidence for interaction with obesity in diabetic patients.

ABSTRACT: Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals.A prospective study (average follow-up, 37 months) was conducted for major cardiovascular events (myocardial infarction [MI], stroke, cardiovascular death) from the Gargano Heart Study (GHS; n = 330 with type 2 diabetes and coronary artery disease), the Tor Vergata Atherosclerosis Study (TVAS; n = 141 who had MI), and the Cardiovascular Risk Extended Evaluation in Dialysis (CREED) database (n = 266 with end-stage renal disease). Age at MI was investigated in cross-sectional studies of 339 type 2 diabetic patients (n = 169 from Italy, n = 170 from the U.S.).Incidence of cardiovascular events per 100 person--years was 4.2 in GHS, 10.8 in TVAS, and 11.7 in CREED. Hazard ratios (HRs) for KQ+QQ versus individuals carrying the K121/K121 genotype (KK) individuals were 1.47 (95% CI 0.80-2.70) in GHS, 2.31 (95% CI 1.22-4.34) in TVAS, and 1.36 (95% CI 0.88-2.10) in CREED, and 1.56 (95% CI 1.15-2.12) in the three cohorts combined. In the 395 diabetic patients, the Q121 variant predicted cardiovascular events among obese but not among nonobese individuals (HR 5.94 vs. 0.62, P = 0.003 for interaction). A similar synergism was observed in cross-sectional studies, with age at MI being 3 years younger in Q121 carriers than in KK homozygotes among obese but not among nonobese patients (P = 0.035 for interaction).The ENPP1 K121Q polymorphism is an independent predictor of major cardiovascular events in high-risk individuals. In type 2 diabetes, this effect is exacerbated by obesity. Future larger studies are needed to confirm our finding.

SUBMITTER: Bacci S

PROVIDER: S-EPMC3046818 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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The ENPP1 Q121 variant predicts major cardiovascular events in high-risk individuals: evidence for interaction with obesity in diabetic patients.

Bacci Simonetta S Rizza Stefano S Prudente Sabrina S Spoto Belinda B Powers Christine C Facciorusso Antonio A Pacilli Antonio A Lauro Davide D Testa Alessandra A Zhang Yuan-Yuan YY Di Stolfo Giuseppe G Mallamaci Francesca F Tripepi Giovanni G Xu Rui R Mangiacotti Davide D Aucella Filippo F Lauro Renato R Gervino Ernest V EV Hauser Thomas H TH Copetti Massimiliano M De Cosmo Salvatore S Pellegrini Fabio F Zoccali Carmine C Federici Massimo M Doria Alessandro A Trischitta Vincenzo V

Diabetes 20110131 3

<h4>Objective</h4>Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals.<h4>Research design and methods</h4>A prospective study (average follow-up, 37 months) was conducted for major cardiovascular events (myocardial infarction [MI], stroke, cardiovascular death) from the Gargano Heart Study (GHS; n = 330 with type 2 diabetes and co ...[more]

PMID: 21282363

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Project description:The Coptic clergy, due to their specific work involving interaction with many people, could be subjected to increased risk of infection from COVID-19. The aim of this study, a sub-study of the COVID-19-CVD international study of the impact of the pandemic on the cardiovascular system, was to assess the prevalence of COVID-19 among Coptic priests and to identify predictors of clinical adverse events. Participants were geographically divided into three groups: Group-I: Europe and USA, Group II: Northern Egypt, and Group III: Southern Egypt. Participants' demographic indices, cardiovascular risk factors, possible source of infection, number of liturgies, infection management, and major adverse events (MAEs), comprising death, or mechanical ventilation, were assessed. Out of the 1570 clergy serving in 25 dioceses, 255 (16.2%) were infected. Their mean age was 49.5 ± 12 years and mean weekly number of liturgies was 3.44 ± 1.0. The overall prevalence rate was 16.2% and did not differ between Egypt as a whole and overseas (p = 0.23). Disease prevalence was higher in Northern Egypt clergy compared with Europe and USA combined (18.4% vs. 12.1%, p = 0.03) and tended to be higher than in Southern Egypt (18.4% vs. 13.6%, p = 0.09). Ten priests (3.92%) died of COVID-19-related complications, and 26 (10.2) suffered a MAE. The clergy from Southern Egypt were more obese, but the remaining risk factors were less prevalent compared with those in Europe and USA (p = 0.01). In multivariate analysis, obesity (OR = 4.180; 2.479 to 12.15; p = 0.01), age (OR = 1.055; 0.024 to 1.141; p = 0.02), and systemic hypertension (OR = 1.931; 1.169 to 2.004; p = 0.007) predicted MAEs. Obesity was the most powerful independent predictor of MAE in Southern Egypt and systemic hypertension in Northern Egypt (p < 0.05 for both). Obesity is very prevalent among Coptic clergy and seems to be the most powerful independent predictor of major COVID-19-related adverse events. Coptic clergy should be encouraged to follow the WHO recommendations for cardiovascular disease and COVID-19 prevention.

Project description:AimsConcern about the cardiovascular safety of coronavirus disease 2019 (COVID-19) vaccines among individuals with cardiovascular disease (CVD) may lead to vaccine hesitancy. We sought to assess the association between two COVID-19 vaccines, BNT162b2 and CoronaVac, and the risk of major adverse cardiovascular events (MACE) in individuals with established CVD.Methods and resultsWe identified individuals with a history of CVD before 23 February 2021 and a diagnosis of MACE between 23 February 2021 and 31 January 2022 in Hong Kong. MACE was defined as a composite of myocardial infarction, stroke, revascularization, and cardiovascular death. Electronic health records from the Hong Kong Hospital Authority were linked to vaccination records from the Department of Health. A self-controlled case-series method was used to evaluate the risk of MACE for 0-13 and 14-27 days after two doses of COVID-19 vaccine. We estimated incidence rate ratios (IRRs) to compare the risk of MACE between each risk period and the baseline period. A total of 229 235 individuals with CVD were identified, of which 1764 were vaccinated and had a diagnosis of MACE during the observation period (BNT162b2 = 662; CoronaVac = 1102). For BNT162b2, IRRs were 0.48 [95% confidence interval (CI) 0.23-1.02] for the first dose and 0.87 (95% CI 0.50-1.52) for the second dose during the 0-13 days risk period, 0.40 (95% CI 0.18-0.93) for the first dose and 1.13 (95% CI 0.70-1.84) for the second dose during the 14-27 days risk period. For CoronaVac, the IRRs were 0.43 (95% CI 0.24-0.75) for the first dose and, 0.73 (95% CI 0.46-1.16) for the second dose during the 0-13 days risk period, 0.54 (95% CI 0.33-0.90) for the first dose and 0.83 (95% CI 0.54-1.29) for the second dose during the 14-27 days risk period. Consistent results were found in subgroup analyses for different sexes, age groups and different underlying cardiovascular conditions.ConclusionOur findings showed no evidence of an increased risk of MACE after vaccination with BNT162b2 or CoronaVac in patients with CVD. Future research is required to monitor the risk after the third dose of each vaccine.

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Dataset Information

The ENPP1 Q121 variant predicts major cardiovascular events in high-risk individuals: evidence for interaction with obesity in diabetic patients.

Publications

The ENPP1 Q121 variant predicts major cardiovascular events in high-risk individuals: evidence for interaction with obesity in diabetic patients.

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