TY - JOUR
T1 - Pseudouridine and N-formylmethionine associate with left ventricular mass index
T2 - Metabolome-wide association analysis of cardiac remodeling
AU - Razavi, Alexander C.
AU - Bazzano, Lydia A.
AU - He, Jiang
AU - Li, Shengxu
AU - Fernandez, Camilo
AU - Whelton, Seamus P.
AU - Krousel-Wood, Marie
AU - Nierenberg, Jovia L.
AU - Shi, Mengyao
AU - Li, Changwei
AU - Mi, Xuenan
AU - Kinchen, Jason
AU - Kelly, Tanika N.
N1 - Funding Information:
This research was supported by the National Institute on Aging as well as the National Heart, Lung, and Blood Institute of the National Institutes of Health under grant numbers R21AG051914 (Principal Investigator, Tanika N. Kelly), 5R01AG041200-05 (Principal Investigator, Lydia A. Bazzano), and P20GM109036 (Principal Investigator, Jiang He). Alexander C. Razavi is currently funded through a predoctoral fellowship training grant supported by the National Heart, Lung, and Blood Institute under grant number F30HL147486 .
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/3
Y1 - 2020/3
N2 - Background: Heart failure (HF) is the fastest growing form of cardiovascular disease both nationally and globally, underlining a need to phenotype subclinical HF intermediaries to improve primary prevention. Objectives: We aimed to identify novel metabolite associations with left ventricular (LV) remodeling, one upstream HF intermediary, among a community-based cohort of individuals. Methods: We examined 1052 Bogalusa Heart Study participants (34.98% African American, 57.41% female, aged 33.6–57.5 years). Measures of LV mass and relative wall thickness (RWT) were obtained using two-dimensional-guided echocardiographic measurements via validated eqs. LV mass was indexed to height2.7 to calculate left ventricular mass index (LVMI). Untargeted metabolomic analysis of fasting serum samples was conducted. In combined and ethnicity-stratified analyses, multivariable linear and multinomial logistic regression models tested the associations of metabolites with the continuous LVMI and RWT and categorical LV geometry phenotypes, respectively, after adjusting for demographic and traditional cardiovascular disease risk factors. Results: Pseudouridine (B = 1.38; p = 3.20 × 10−5) and N-formylmethionine (B = 1.65; 3.30 × 10−6) were significantly associated with LVMI in the overall sample as well significant in Caucasians, with consistent effect direction and nominal significance (p <.05) in African Americans. Upon exclusion of individuals with self-report myocardial infarction or congestive HF, we similarly observed a 1.33 g/m2.7 and 1.52 g/m2.7 higher LVMI for each standard deviation increase in pseudouridine and N-formylmethionine, respectively. No significant associations were observed for metabolites with RWT or categorical LV remodeling outcomes. Conclusions: The current analysis identified novel associations of pseudouridine and N-formylmethionine with LVMI, suggesting that mitochondrial-derived metabolites may serve as early biomarkers for LV remodeling and subclinical HF.
AB - Background: Heart failure (HF) is the fastest growing form of cardiovascular disease both nationally and globally, underlining a need to phenotype subclinical HF intermediaries to improve primary prevention. Objectives: We aimed to identify novel metabolite associations with left ventricular (LV) remodeling, one upstream HF intermediary, among a community-based cohort of individuals. Methods: We examined 1052 Bogalusa Heart Study participants (34.98% African American, 57.41% female, aged 33.6–57.5 years). Measures of LV mass and relative wall thickness (RWT) were obtained using two-dimensional-guided echocardiographic measurements via validated eqs. LV mass was indexed to height2.7 to calculate left ventricular mass index (LVMI). Untargeted metabolomic analysis of fasting serum samples was conducted. In combined and ethnicity-stratified analyses, multivariable linear and multinomial logistic regression models tested the associations of metabolites with the continuous LVMI and RWT and categorical LV geometry phenotypes, respectively, after adjusting for demographic and traditional cardiovascular disease risk factors. Results: Pseudouridine (B = 1.38; p = 3.20 × 10−5) and N-formylmethionine (B = 1.65; 3.30 × 10−6) were significantly associated with LVMI in the overall sample as well significant in Caucasians, with consistent effect direction and nominal significance (p <.05) in African Americans. Upon exclusion of individuals with self-report myocardial infarction or congestive HF, we similarly observed a 1.33 g/m2.7 and 1.52 g/m2.7 higher LVMI for each standard deviation increase in pseudouridine and N-formylmethionine, respectively. No significant associations were observed for metabolites with RWT or categorical LV remodeling outcomes. Conclusions: The current analysis identified novel associations of pseudouridine and N-formylmethionine with LVMI, suggesting that mitochondrial-derived metabolites may serve as early biomarkers for LV remodeling and subclinical HF.
KW - Biomarkers
KW - Cardiovascular
KW - Epidemiology
KW - Heart failure
KW - Metabolomics
KW - N-formylmethionine
KW - Pseudouridine
KW - Ventricular remodeling
UR - http://www.scopus.com/inward/record.url?scp=85079887975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079887975&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2020.02.005
DO - 10.1016/j.yjmcc.2020.02.005
M3 - Article
C2 - 32057737
AN - SCOPUS:85079887975
SN - 0022-2828
VL - 140
SP - 22
EP - 29
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
ER -