Relations of Long-term and Contemporary Lipid Levels and Lipid Genetic Risk Scores with Coronary Artery Calcium in the Framingham Heart Study

Overview

Journal J Am Coll Cardiol

Specialty Cardiology & Vascular Diseases

Date 2012 Nov 13

PMID 23141485

Citations 23

Authors

Connie W Tsao

Sarah Rosner Preis

Gina M Peloso

Shih-Jen Hwang

Sekar Kathiresan

Caroline S Fox

L Adrienne Cupples

Udo Hoffmann

Christopher J ODonnell

Affiliations

Soon will be listed here.

Abstract

Objectives: This study evaluated the association of timing of lipid levels and lipid genetic risk score (GRS) with subclinical atherosclerosis.

Background: Atherosclerosis is a slowly progressive disorder influenced by suboptimal lipid levels. Long-term versus contemporary lipid levels may more strongly impact the development of coronary artery calcium (CAC).

Methods: Framingham Heart Study (FHS) Offspring Cohort participants (n = 1,156, 44% male, 63 ± 9 years) underwent serial fasting lipids (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein, and triglycerides), Exam 1 (1971 to 1975) to Exam 7 (1998 to 2001). FHS Third Generation Cohort participants (n = 1,954, 55% male, 45 ± 6 years) had fasting lipid profiles assessed, 2002 to 2005. Computed tomography (2002 to 2005) measured CAC. Lipid GRSs were computed from significantly associated single-nucleotide polymorphisms. The association between early, long-term average, and contemporary lipids, and lipid GRS with elevated CAC was assessed using logistic regression.

Results: In FHS Offspring, Exam 1 and long-term average as compared with Exam 7 lipid measurements, including untreated lipid levels, were strongly associated with elevated CAC. In the FHS Third Generation, contemporary lipids were associated with CAC. The LDL-C GRS was associated with CAC (age-/sex-adjusted odds ratio: 1.14, 95% confidence interval: 1.00 to 1.29, p = 0.04). However, addition of the GRS to the lipid models did not result in a significant increase in the odds ratio or C-statistic for any lipid measure.

Conclusions: Early and long-term average lipid levels, as compared with contemporary measures, are more strongly associated with elevated CAC. Lipid GRS was associated with lipid levels but did not predict elevated CAC. Adult early and long-term average lipid levels provide important information when assessing subclinical atherosclerosis and cardiovascular risk.

Citing Articles

Serum Lipoproteins Are Associated With Coronary Atherosclerosis in Asymptomatic U.S. Adults Without Traditional Risk Factors.

Faridi K, Lahan S, Budoff M, Cury R, Feldman T, Pan A JACC Adv. 2024; 3(7):101049.

PMID: 39129991 PMC: 11312344. DOI: 10.1016/j.jacadv.2024.101049.

The role of coffee and potential mediators in subclinical atherosclerosis: insights from Mendelian randomization study.

Yang Q, Yuan Y, Lyu D, Zhuang R, Xue D, Niu C Front Nutr. 2024; 11:1405353.

PMID: 39119461 PMC: 11309031. DOI: 10.3389/fnut.2024.1405353.

Clusters of multidimensional exercise response patterns and estimated heart failure risk in the Framingham Heart Study.

Miller P, Gajjar P, Mitchell G, Khan S, Vasan R, Larson M ESC Heart Fail. 2024; 11(5):3279-3289.

PMID: 38943268 PMC: 11424363. DOI: 10.1002/ehf2.14797.

Clusters of longitudinal risk profile trajectories are associated with cardiometabolic diseases: Results from the population-based KORA cohort.

Niedermayer F, Schauberger G, Rathmann W, Klug S, Thorand B, Peters A PLoS One. 2024; 19(3):e0300966.

PMID: 38547172 PMC: 10977748. DOI: 10.1371/journal.pone.0300966.

Low-Density Lipoprotein Cholesterol Is Predominantly Associated With Atherosclerotic Cardiovascular Disease Events in Patients With Evidence of Coronary Atherosclerosis: The Western Denmark Heart Registry.

Mortensen M, Dzaye O, Botker H, Jensen J, Maeng M, Bentzon J Circulation. 2023; 147(14):1053-1063.

PMID: 36621817 PMC: 10073288. DOI: 10.1161/CIRCULATIONAHA.122.061010.

References

Kannel W, Feinleib M, MCNAMARA P, Garrison R, CASTELLI W . An investigation of coronary heart disease in families. The Framingham offspring study. Am J Epidemiol. 1979; 110(3):281-90. DOI: 10.1093/oxfordjournals.aje.a112813. View

Allison M, Pavlinac P, Wright C . The differential associations between HDL, non-HDL and total cholesterols and atherosclerotic calcium deposits in multiple vascular beds. Atherosclerosis. 2006; 194(2):e87-94. DOI: 10.1016/j.atherosclerosis.2006.10.006. View

Parikh N, Hwang S, Larson M, Cupples L, Fox C, Manders E . Parental occurrence of premature cardiovascular disease predicts increased coronary artery and abdominal aortic calcification in the Framingham Offspring and Third Generation cohorts. Circulation. 2007; 116(13):1473-81. DOI: 10.1161/CIRCULATIONAHA.107.705202. View

Detrano R, Guerci A, Carr J, Bild D, Burke G, Folsom A . Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008; 358(13):1336-45. DOI: 10.1056/NEJMoa072100. View

Thanassoulis G, Vasan R . Genetic cardiovascular risk prediction: will we get there?. Circulation. 2010; 122(22):2323-34. PMC: 3075800. DOI: 10.1161/CIRCULATIONAHA.109.909309. View

Ross R . Atherosclerosis--an inflammatory disease. N Engl J Med. 1999; 340(2):115-26. DOI: 10.1056/NEJM199901143400207. View

Thanassoulis G, Peloso G, Pencina M, Hoffmann U, Fox C, Cupples L . A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet. 2012; 5(1):113-21. PMC: 3292865. DOI: 10.1161/CIRCGENETICS.111.961342. View

Loria C, Liu K, Lewis C, Hulley S, Sidney S, Schreiner P . Early adult risk factor levels and subsequent coronary artery calcification: the CARDIA Study. J Am Coll Cardiol. 2007; 49(20):2013-20. DOI: 10.1016/j.jacc.2007.03.009. View

Greenland P, Alpert J, Beller G, Benjamin E, Budoff M, Fayad Z . 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2010; 122(25):e584-636. DOI: 10.1161/CIR.0b013e3182051b4c. View

10.

Lee Splansky G, Corey D, Yang Q, Atwood L, Cupples L, Benjamin E . The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: design, recruitment, and initial examination. Am J Epidemiol. 2007; 165(11):1328-35. DOI: 10.1093/aje/kwm021. View

11.

Manolio T, Collins F, Cox N, Goldstein D, Hindorff L, Hunter D . Finding the missing heritability of complex diseases. Nature. 2009; 461(7265):747-53. PMC: 2831613. DOI: 10.1038/nature08494. View

12.

Hoffmann U, Massaro J, Fox C, Manders E, ODonnell C . Defining normal distributions of coronary artery calcium in women and men (from the Framingham Heart Study). Am J Cardiol. 2008; 102(9):1136-41, 1141.e1. PMC: 3065378. DOI: 10.1016/j.amjcard.2008.06.038. View

13.

Pletcher M, Bibbins-Domingo K, Liu K, Sidney S, Lin F, Vittinghoff E . Nonoptimal lipids commonly present in young adults and coronary calcium later in life: the CARDIA (Coronary Artery Risk Development in Young Adults) study. Ann Intern Med. 2010; 153(3):137-46. PMC: 3468943. DOI: 10.7326/0003-4819-153-3-201008030-00004. View

14.

Davis P, Dawson J, RILEY W, Lauer R . Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: The Muscatine Study. Circulation. 2001; 104(23):2815-9. DOI: 10.1161/hc4601.099486. View

15.

Psaty B, ODonnell C, Gudnason V, Lunetta K, Folsom A, Rotter J . Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circ Cardiovasc Genet. 2009; 2(1):73-80. PMC: 2875693. DOI: 10.1161/CIRCGENETICS.108.829747. View

16.

HELLER D, de Faire U, Pedersen N, Dahlen G, McClearn G . Genetic and environmental influences on serum lipid levels in twins. N Engl J Med. 1993; 328(16):1150-6. DOI: 10.1056/NEJM199304223281603. View

17.

Paramsothy P, Knopp R, Bertoni A, Blumenthal R, Wasserman B, Tsai M . Association of combinations of lipid parameters with carotid intima-media thickness and coronary artery calcium in the MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2010; 56(13):1034-41. DOI: 10.1016/j.jacc.2010.01.073. View

18.

Kathiresan S, Manning A, Demissie S, DAgostino R, Surti A, Guiducci C . A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. BMC Med Genet. 2007; 8 Suppl 1:S17. PMC: 1995614. DOI: 10.1186/1471-2350-8-S1-S17. View

19.

Tikkanen E, Tuovinen T, Widen E, Lehtimaki T, Viikari J, Kahonen M . Association of known loci with lipid levels among children and prediction of dyslipidemia in adults. Circ Cardiovasc Genet. 2011; 4(6):673-80. DOI: 10.1161/CIRCGENETICS.111.960369. View

20.

Mahoney L, Burns T, Stanford W, Thompson B, Witt J, Rost C . Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study. J Am Coll Cardiol. 1996; 27(2):277-84. DOI: 10.1016/0735-1097(95)00461-0. View