Person:

Hauser, Thomas

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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.). RESULTS: 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). CONCLUSIONS: 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.

Background: The relationship between pulmonary vein (PV) anatomy and successful catheter ablation of atrial fibrillation (AF) is poorly understood Methods: First-pass contrast enhanced PV magnetic resonance angiography was performed in 71 consecutive patients prior to PV isolation. PV diameter and cross-sectional area (CSA) were measured prior to PV isolation. Any symptomatic or asymptomatic AF >10s was considered a recurrence. Early recurrence was defined as recurrent AF ≤30 days after PV isolation, while late recurrence of AF was defined as recurrent AF >30 days after. Results: At 1 year, 57 % had any recurrence of AF while 41 % had late recurrence of AF. Study subjects with one or more PV diameter in the top 10th percentile had trend toward more early recurrent AF (HR 1.99, p = 0.053). Study subjects with one or more PV CSA in the top 10th percentile had more late recurrent AF (HR 2.25, p = 0.039) and a trend toward more early recurrent AF (HR 1.94, p = 0.064). With multivariate analysis, PV size was not associated with early recurrent AF, but late recurrent AF was associated with one or more large PV, increased left atrial size, and non-paroxysmal AF. Study subjects with all three of these risk factors had a 100 % rate of late recurrent AF at 1 year, while those with none had a 7 % rate of late recurrent AF. Conclusions: Larger PV size is independently associated with more late recurrent AF after PV isolation. Determination of PV size prior to PV isolation may predict procedural success.