Associations of Metabolic Changes and Polygenic Risk Scores with Cardiovascular Outcomes and All-cause Mortality Across BMI Categories: a Prospective Cohort Study

Overview

Journal Cardiovasc Diabetol

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
Endocrinology

Date 2024 Jul 4

PMID 38965592

Authors

Cancan Li

Xiaoni Meng

Jie Zhang

Haotian Wang

Huimin Lu

Meiling Cao

Shengzhi Sun

Youxin Wang

Affiliations

Soon will be listed here.

Abstract

Background: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories.

Methods: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m, 25 ≤ BMI < 30 kg/m, and BMI ≥ 30 kg/m, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories.

Results: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (P < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed.

Conclusions: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.

References

Katsimardou A, Imprialos K, Stavropoulos K, Sachinidis A, Doumas M, Athyros V . Hypertension in Metabolic Syndrome: Novel Insights. Curr Hypertens Rev. 2019; 16(1):12-18. DOI: 10.2174/1573402115666190415161813. View

Wildman R, Muntner P, Reynolds K, McGinn A, Rajpathak S, Wylie-Rosett J . The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999-2004). Arch Intern Med. 2008; 168(15):1617-24. DOI: 10.1001/archinte.168.15.1617. View

Gami A, Witt B, Howard D, Erwin P, Gami L, Somers V . Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol. 2007; 49(4):403-14. DOI: 10.1016/j.jacc.2006.09.032. View

Alberti K, Eckel R, Grundy S, Zimmet P, Cleeman J, Donato K . Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation;.... Circulation. 2009; 120(16):1640-5. DOI: 10.1161/CIRCULATIONAHA.109.192644. View

Wang L, Song L, Li D, Zhou Z, Chen S, Yang Y . Ideal Cardiovascular Health Metric and Its Change With Lifetime Risk of Cardiovascular Diseases: A Prospective Cohort Study. J Am Heart Assoc. 2021; 10(22):e022502. PMC: 8751933. DOI: 10.1161/JAHA.121.022502. View

Cleland C, Ferguson S, Ellis G, Hunter R . Validity of the International Physical Activity Questionnaire (IPAQ) for assessing moderate-to-vigorous physical activity and sedentary behaviour of older adults in the United Kingdom. BMC Med Res Methodol. 2018; 18(1):176. PMC: 6303992. DOI: 10.1186/s12874-018-0642-3. View

Yeh T, Chen H, Tsai S, Lin C, Liu S, Chien K . The Relationship between Metabolically Healthy Obesity and the Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis. J Clin Med. 2019; 8(8). PMC: 6723711. DOI: 10.3390/jcm8081228. View

Walli-Attaei M, Rosengren A, Rangarajan S, Breet Y, Abdul-Razak S, Al Sharief W . Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study. Lancet. 2022; 400(10355):811-821. DOI: 10.1016/S0140-6736(22)01441-6. View

Li X, Ma H, Wang X, Feng H, Qi L . Life's Essential 8, Genetic Susceptibility, and Incident Cardiovascular Disease: A Prospective Study. Arterioscler Thromb Vasc Biol. 2023; 43(7):1324-1333. PMC: 10330462. DOI: 10.1161/ATVBAHA.123.319290. View

10.

Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J . UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015; 12(3):e1001779. PMC: 4380465. DOI: 10.1371/journal.pmed.1001779. View

11.

Zhang Q, Zhou Y, Gao X, Wang C, Zhang S, Wang A . Ideal cardiovascular health metrics and the risks of ischemic and intracerebral hemorrhagic stroke. Stroke. 2013; 44(9):2451-6. DOI: 10.1161/STROKEAHA.113.678839. View

12.

Eckel N, Li Y, Kuxhaus O, Stefan N, Hu F, Schulze M . Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses' Health Study): 30 year follow-up from a prospective cohort study. Lancet Diabetes Endocrinol. 2018; 6(9):714-724. DOI: 10.1016/S2213-8587(18)30137-2. View

13.

Dugani S, Moorthy M, Li C, Demler O, Alsheikh-Ali A, Ridker P . Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women. JAMA Cardiol. 2021; 6(4):437-447. PMC: 7818181. DOI: 10.1001/jamacardio.2020.7073. View

14.

Mongraw-Chaffin M, Foster M, Anderson C, Burke G, Haq N, Kalyani R . Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk. J Am Coll Cardiol. 2018; 71(17):1857-1865. PMC: 6002856. DOI: 10.1016/j.jacc.2018.02.055. View

15.

Kouvari M, Panagiotakos D, Yannakoulia M, Georgousopoulou E, Critselis E, Chrysohoou C . Transition from metabolically benign to metabolically unhealthy obesity and 10-year cardiovascular disease incidence: The ATTICA cohort study. Metabolism. 2019; 93:18-24. DOI: 10.1016/j.metabol.2019.01.003. View

16.

Stefan N, Kantartzis K, Machann J, Schick F, Thamer C, Rittig K . Identification and characterization of metabolically benign obesity in humans. Arch Intern Med. 2008; 168(15):1609-16. DOI: 10.1001/archinte.168.15.1609. View

17.

Choi S, OReilly P . PRSice-2: Polygenic Risk Score software for biobank-scale data. Gigascience. 2019; 8(7). PMC: 6629542. DOI: 10.1093/gigascience/giz082. View

18.

Arnlov J, Ingelsson E, Sundstrom J, Lind L . Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation. 2009; 121(2):230-6. DOI: 10.1161/CIRCULATIONAHA.109.887521. View

19.

Zhang J, Chen G, Habudele Z, Wang X, Cai M, Li H . Relation of Life's Essential 8 to the genetic predisposition for cardiovascular outcomes and all-cause mortality: results from a national prospective cohort. Eur J Prev Cardiol. 2023; 30(15):1676-1685. DOI: 10.1093/eurjpc/zwad179. View

20.

Hartiala J, Han Y, Jia Q, Hilser J, Huang P, Gukasyan J . Genome-wide analysis identifies novel susceptibility loci for myocardial infarction. Eur Heart J. 2021; 42(9):919-933. PMC: 7936531. DOI: 10.1093/eurheartj/ehaa1040. View