Dataset Information

Lung function, percent emphysema, and QT duration: The Multi-Ethnic Study of Atherosclerosis (MESA) lung study.

ABSTRACT: BACKGROUND:The QT interval on electrocardiogram (ECG) reflects ventricular repolarization; a prolonged QT interval is associated with increased mortality risk. Prior studies suggest an association between chronic obstructive pulmonary disease (COPD) and prolonged QT interval. However, these studies were small and often enrolled hospital-based samples. We tested the hypotheses that lower lung function and increased percent emphysema on computed tomography (CT) are associated with a prolonged QT interval in a general population sample and additionally in those with COPD. METHODS:As part of the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, we assessed spirometry, full-lung CT scans, and ECGs in participants aged 45-84 years. The QT on ECGs was corrected for heart rate (QTc) using the Framingham formula. QTc values = 460 msec in women and ?450 msec in men were considered abnormal (prolonged QTC). Multivariate regression models were used to examine the cross-sectional association between pulmonary measures and QTC. RESULTS: The mean age of the sample of 2585 participants was 69 years, and 47% were men. There was an inverse association between FEV1%, FVC%, FEV1/FVC%, emphysema, QTc duration and prolonged QTc. Gender was a significant interaction term, even among never smokers. Having severe COPD was also associated with QTc prolongation. CONCLUSIONS:Our analysis revealed a significant association between lower lung function and longer QTc in men but not in women in a population-based sample. Our findings suggest the possibility of gender differences in the risk of QTc-associated arrhythmias in a population-based sample.

SUBMITTER: Armstrong HF

PROVIDER: S-EPMC5302224 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Lung function, percent emphysema, and QT duration: The Multi-Ethnic Study of Atherosclerosis (MESA) lung study.

Armstrong Hilary F HF Lovasi Gina S GS Soliman Elsayed Z EZ Heckbert Susan R SR Psaty Bruce M BM Austin John H M JH Krishnan Jerry A JA Hoffman Eric A EA Johnson Craig C Budoff Matthew J MJ Watson Karol E KE Barr R Graham RG

Respiratory medicine 20161208

<h4>Background</h4>The QT interval on electrocardiogram (ECG) reflects ventricular repolarization; a prolonged QT interval is associated with increased mortality risk. Prior studies suggest an association between chronic obstructive pulmonary disease (COPD) and prolonged QT interval. However, these studies were small and often enrolled hospital-based samples. We tested the hypotheses that lower lung function and increased percent emphysema on computed tomography (CT) are associated with a prolon ...[more]

PMID: 28137484

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Project description:RationalePulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering.ObjectivesTo complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States.MethodsWe determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than -950 HU on cardiac scans. Genetic analyses were reported combined across four race/ethnic groups: non-Hispanic white (n = 2,587), African American (n = 2,510), Hispanic (n = 2,113), and Chinese (n = 704) and stratified by race and ethnicity.Measurements and main resultsAmong 7,914 participants, we identified regions at genome-wide significance for percent emphysema in or near SNRPF (rs7957346; P = 2.2 × 10(-8)) and PPT2 (rs10947233; P = 3.2 × 10(-8)), both of which replicated in an additional 6,023 individuals of European ancestry. Both single-nucleotide polymorphisms were previously implicated as genes influencing lung function, and analyses including lung function revealed independent associations for percent emphysema. Among Hispanics, we identified a genetic locus for upper-lower lobe ratio near the α-mannosidase-related gene MAN2B1 (rs10411619; P = 1.1 × 10(-9); minor allele frequency [MAF], 4.4%). Among Chinese, we identified single-nucleotide polymorphisms associated with upper-lower lobe ratio near DHX15 (rs7698250; P = 1.8 × 10(-10); MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10(-8); MAF, 2.6%), which acts on α-linked mannose. Among African Americans, a locus near a third α-mannosidase-related gene, MAN1C1 (rs12130495; P = 9.9 × 10(-6); MAF, 13.3%) was associated with percent emphysema.ConclusionsOur results suggest that some genes previously identified as influencing lung function are independently associated with emphysema rather than lung function, and that genes related to α-mannosidase may influence risk of emphysema.

Dataset Information

Lung function, percent emphysema, and QT duration: The Multi-Ethnic Study of Atherosclerosis (MESA) lung study.

Publications

Lung function, percent emphysema, and QT duration: The Multi-Ethnic Study of Atherosclerosis (MESA) lung study.

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