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Background: Atrial fibrillation (AF) diminishes quality of life and accounts for approximately one-third of all strokes. Studies have associated mitochondrial dysfunction with both AF and telomere length (TL).Objective: The purpose of this study was to test the hypothesis of a relationship between AF and TL.Methods: Blood was collected from consenting participants in the Intermountain Heart Collaborative Study (n = 3576) and DNA extracted. TL was determined by multiplex quantitative polymerase chain reaction, normalized to a single copy gene, and reported as telomere/single gene ratio (t/s). Patient information was extracted from Intermountain Healthcare's electronic records database. Prevalent AF was determined by discharge ICD-9 code. AF subtype (paroxysmal [Px], persistent [Ps], long-standing persistent/permanent [Pm]) was determined by chart review.Results: The t/s decreased with age (P <.00001). Subjects with a history of AF (n = 379 [10.6%] had shorter telomeres (mean t/s ± SD = 0.87 ± 0.29) compared to subjects without AF (mean t/s 0.95 ± 0.32, P <.0001). The association remained after adjustment for age (P = .017) and cardiovascular risk factors (P = .016). AF subtype was determined for 277 subjects; 110 (39.7%) had Px AF, 65 (23.5%) Ps, and 102 (36.8%) Pm AF. Mean t/s did not differ between Ps, Pm, and subjects without AF (0.94 ± 0.40, 0.94 ± 0.27, and 0.95 ± 0.32, respectively). However, the mean t/s for Px (0.81 ± 0.22) was significantly shorter than for Ps (P = .026), Pm (P = .004), or subjects without AF (P <.0001).Conclusion: The present study supports an association between Px AF and TL. Short TL may be a previously unrecognized risk factor for AF with potential applications in diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Lipoprotein(a) (Lp[a]) has gained attention as a heritable coronary artery disease (CAD) risk factor and therapeutic target. Two genetic variants in the LPA gene have been reported to influence Lp(a) levels and increase CAD risk. The aim of this study was to prospectively test these variants for their associations with Lp(a) and CAD risk. Participants (n = 1,400) in the Intermountain Heart Collaborative Study Registry who had Lp(a) cholesterol levels determined at coronary angiography were genotyped for rs3798220 and rs1045587 in LPA. Variants were detected by Taqman polymerase chain reaction. Chi-square and linear and logistic regression tests were used as appropriate among genotypes for Lp(a) and angiographic CAD. Age averaged 63 years; 65% were men; and severe CAD was present in 57%, mild CAD in 12%, and no CAD in 31%. Minor allele frequencies were 0.023 for rs3798220 and 0.090 for rs10455872. In multivariate modeling, only rs10455872 (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.67 to 3.33, p = 1.75 × 10L-9) and rs3798220 (OR 1.99, 95% CI 0.99 to 4.00, p = 0.065) contributed to the prediction of elevated Lp(a) cholesterol. Lp(a) cholesterol was weakly associated with CAD (OR 1.17, 95% CI 1.00 to 1.37, p = 0.055). Rs10455872 strongly predicted prevalent CAD (per allele OR 1.43, 95% CI 1.07 to 1.91, p = 0.0172); the effect size for the rare rs3798220 variant was similar (dominant OR 1.47, 95% CI 0.81 to 2.67, p = 0.20), but power was limited to demonstrate significance. The combined genotype explained only a small percentage (≤4%) of variability in Lp(a) cholesterol and prevalence of angiographic CAD. In conclusion, heritable contributions of LPA rs10455872 and rs3798220 to Lp(a) cholesterol levels and to angiographic CAD were prospectively assessed in this study. The percentage of intersubject variability in Lp(a) cholesterol and the percentage of prevalent CAD explained were small. [ABSTRACT FROM AUTHOR]