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Nonoptimal Lipids Commonly Present in Young Adults and Coronary Calcium Later in Life: The CARDIA (Coronary Artery Risk Development in Young Adults) Study

Mark J. Pletcher, MD, MPH; Kirsten Bibbins-Domingo, PhD, MD; Kiang Liu, PhD; Steve Sidney, MD, MPH; Feng Lin, MS; Eric Vittinghoff, PhD; and Stephen B. Hulley, MD, MPH
[+] Article, Author, and Disclosure Information

From University of California, San Francisco, San Francisco, and Kaiser Permanente Division of Research, Oakland, California, and Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Grant Support: By the University of Alabama at Birmingham Coordinating Center (grant N01-HC-95095); University of Alabama at Birmingham Field Center (grant N01-HC-48047); University of Minnesota Field Center and Diet Reading Center (year 20 examination) (grant N01-HC-48048); Northwestern University Field Center (grant N01-HC-48049); Kaiser Foundation Research Institute (grant N01-HC-48050); University of California, Irvine, Echocardiography Reading Center (years 5 and 10) (grant N01-HC-45134); Harbor-University of California, Los Angeles, Research Education Institute, Computed Tomography Reading Center (year 15 examination) (grant N01-HC-05187); Wake Forest University (year 20 examination) (grant N01-HC-45205); and New England Medical Center (year 20 examination) (grant N01-HC-45204 from the National Heart, Lung and Blood Institute).

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-0248.

Reproducible Research Statement:Study protocol: Available at www.cardia.dopm.uab.edu/. Statistical code: Available from Dr. Pletcher (e-mail, mpletcher@epi.ucsf.edu). Data set: A limited-access data set is available through the National Heart, Lung, and Blood Institute at www.nhlbi.nih.gov/resources/deca/descriptions/cardia.htm.

Requests for Single Reprints: Mark J. Pletcher, MD, MPH, Department of Epidemiology and Biostatistics, University of California, San Francisco, 185 Berry Street, Suite 5700, San Francisco, CA 94107; e-mail, mpletcher@epi.ucsf.edu.

Current Author Addresses: Drs. Pletcher, Vittinghoff, and Hulley and Mr. Lin: Department of Epidemiology and Biostatistics, University of California, San Francisco, 185 Berry Street, Suite 5700, San Francisco, CA 94107.

Dr. Bibbins-Domingo: Department of Medicine, University of California, San Francisco, Box 1364, San Francisco, CA 94143-1364.

Dr. Liu: Feinberg School of Medicine, Northwestern University, 680 North Lake Shore Drive, Suite 1102, Chicago, IL 60611-4402.

Dr. Sidney: Division of Research, Kaiser Permanente, 2000 Broadway, Oakland, CA 94612.

Author Contributions: Conception and design: M.J. Pletcher, K. Bibbins-Domingo, S.B. Hulley.

Analysis and interpretation of the data: M.J. Pletcher, K. Bibbins-Domingo, K. Liu, E. Vittinghoff, S.B. Hulley.

Drafting of the article: M.J. Pletcher, K. Bibbins-Domingo, E. Vittinghoff, S.B. Hulley.

Critical revision of the article for important intellectual content: M.J. Pletcher, S. Sidney, E. Vittinghoff, S.B. Hulley.

Final approval of the article: M.J. Pletcher, S. Sidney, F. Lin, E. Vittinghoff, S.B. Hulley.

Provision of study materials or patients: S.B. Hulley.

Statistical expertise: F. Lin, E. Vittinghoff, S.B. Hulley.

Obtaining of funding: M.J. Pletcher, K. Liu, S. Sidney, S.B. Hulley.

Administrative, technical, or logistic support: S. Sidney.

Collection and assembly of data: S.B. Hulley.

Ann Intern Med. 2010;153(3):137-146. doi:10.7326/0003-4819-153-3-201008030-00004
Text Size: A A A

Background: Dyslipidemia causes coronary heart disease in middle-aged and elderly adults, but the consequences of lipid exposure during young adulthood are unclear.

Objective: To assess whether nonoptimal lipid levels during young adulthood cause atherosclerotic changes that persist into middle age.

Design: Prospective cohort study.

Setting: 4 cities in the United States.

Participants: 3258 participants from the 5115 black and white men and women recruited at age 18 to 30 years in 1985 to 1986 for the CARDIA (Coronary Artery Risk Development in Young Adults) study.

Measurements: Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and coronary calcium. Time-averaged cumulative exposures to lipids between age 20 and 35 years were estimated by using repeated serum lipid measurements over 20 years in the CARDIA study; these measurements were then related to coronary calcium scores assessed later in life (45 years [SD, 4]).

Results: 2824 participants (87%) had nonoptimal levels of LDL cholesterol (≥2.59 mmol/L [≥100 mg/dL]), HDL cholesterol (<1.55 mmol/L [<60 mg/dL]), or triglycerides (≥1.70 mmol/L [≥150 mg/dL]) during young adulthood. Coronary calcium prevalence 2 decades later was 8% in participants who maintained optimal LDL levels (<1.81 mmol/L [<70 mg/dL]), and 44% in participants with LDL cholesterol levels of 4.14 mmol/L (160 mg/dL) or greater (P < 0.001). The association was similar across race and sex and strongly graded, with odds ratios for coronary calcium of 1.5 (95% CI, 0.7 to 3.3) for LDL cholesterol levels of 1.81 to 2.56 mmol/L (70 to 99 mg/dL), 2.4 (CI, 1.1 to 5.3) for levels of 2.59 to 3.34 mmol/L (100 to 129 mg/dL), 3.3 (CI, 1.3 to 7.8) for levels of 3.37 to 4.12 mmol/L (130 to 159 mg/dL), and 5.6 (CI, 2.0 to 16) for levels of 4.14 mmol/L (160 mg/dL) or greater, compared with levels less than 1.81 mmol/L (<70 mg/dL), after adjustment for lipid exposure after age 35 years and other coronary risk factors. Both LDL and HDL cholesterol levels were independently associated with coronary calcium after participants who were receiving lipid-lowering medications or had clinically abnormal lipid levels were excluded.

Limitation: Coronary calcium, although a strong predictor of future coronary heart disease, is not a clinical outcome.

Conclusion: Nonoptimal levels of LDL and HDL cholesterol during young adulthood are independently associated with coronary atherosclerosis 2 decades later.

Primary Funding Source: National Heart, Lung, and Blood Institute.


Grahic Jump Location
Figure 1.
Coronary calcium score distribution in middle age with increasing exposure to lipids before age 35 years.

Cumulative exposures to LDL cholesterol, HDL cholesterol, and triglycerides were estimated by using integrated lipid trajectory analysis (see Methods section) and expressed as a time-averaged value. The association with coronary calcium score category is significant in all cases (P < 0.001). We excluded 10 persons with a positive coronary calcium scan but an unknown coronary calcium score for this figure. HDL = high-density lipoprotein; LDL = low-density lipoprotein.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Prevalence of coronary calcium by lipid exposure before age 35 years, by race and sex.

Cumulative exposures to LDL cholesterol, HDL cholesterol, and triglycerides were estimated by using integrated lipid trajectory analysis (see Methods section) and expressed as a time-averaged value. P values represent the trend for increasing odds of calcification by category. Values above bars are numbers of participants. HDL = high-density lipoprotein; LDL = low-density lipoprotein.

* Subgroup had fewer than 20 participants; estimate not shown.

Grahic Jump Location




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Submit a Comment/Letter
Nonoptimal Lipids Commonly Present in Young Adults and Coronary Calcium Later in Life
Posted on August 6, 2010
Robert A. Peraino
No Affiliation
Conflict of Interest: None Declared

Dear Editor:

In the background to the article the authors claim that dyslipidemia causes coronary heart disease and this is nothing short of outrageous. Their claim ignores clinical observations made since the lipid hypothesis became most popular in the 1970's. Those observations include the following: our obsession with cholesterol has not led to a drop in the incidence or prevalence of atherosclerotic cardiovascular disease. Instead we have a whole lot of really fat people with diabetes and its complications. Twenty-five percent of patients with an acute myocardial infarction have ideal lipid profiles; peole live into their 80's and 90's with calcified blood vessels; the claim that lowering LDL to less than 70 is beneficial ignores the fact that the benefit has nothing to do with LDL, but with prescribing a statin drug. Statins are also anti- inflammatory and inhibit platelet function.

Non-diabetic patients who undergo coronary bypasses for symptomatic coronary disease seem to have no further clinical manifestations, ten and twenty or more years after their procedure, casting grave doubt on the commonly held belief that atherosclerosis is a progressive disease. This fact antedates the widespread use of statins. The drug Vytorin lowers cholesterol but has not been shown to affect the incidence of symptomatic or clinical atherosclerosis. Improved survival with clinical, symptomatic atherosclerosis has nothing to do with lowering cholesterol but is due to better treatments: first bypass surgery, then thrombolysis, and now stent placement. Lowering lipids in dialysis patients does not lead to better outcomes.

The authors own data, Table 1, lists multiple confounding variables that are more prevalent in those who develop coronary calcification and have higher lipid values. It's about time we get off the cholesterol bandwagon and really devote research to finding the cause of damage to blood vessels which makes the injured areas prone to plaque formation.

Conflict of Interest:

None declared

Physiological information is more predictive of coronary events than Anatomical one
Posted on September 20, 2010
Dr.Srikanth Subrahmanya Achanta
No Affiliation
Conflict of Interest: None Declared

I appreciate this wonderful study which gives invaluable information about growing problem in middle aged and young individuals. This study is showing correlation between abnormal lipid levels in young age and persistence of atherosclerotic changes in middle age which is represented by abnormal coronary artery calcium score (CACS).In fact it is a long study with good follow up, but two important things must be emphasized in this context. One is how far coronary calcium score measurement is valid and how good coronary score represents coronary heart disease risk. Ultimately it is the coronary risk burden which should be reduced. Based on the existing data CACS will not aid clinicians in better treating patients or improving their clinical outcomes. There is no proven relationship between coronary artery calcification and the probability of plaque rupture. Calcium scores do not identify the location of specific vulnerable lesions and Substantial non-calcified plaque is frequently present in the absence of coronary artery calcification. So many retrospective studies have shown that acute coronary syndromes are associated with noncalcified and mixed plaques.

In addition to this there are so many factors which influence measurement of CACS which we cannot ignore, like high heart rate may interfere with the image quality of the test, when coronary calcium measured by ultrafast CT it is found a lot of variability in measurements, therefore use of serial CT scans to check the calcium is difficult. Finally in Type 2 diabetes, apoB level is stronger predictor of atherosclerotic burden than LDL cholesterol and other cholesterol parameters. So even though coronary calcium score is one of the promising diagnostic tool for future coronary events one must understand that Calcium is associated with the development of plaques but not in all cases and the correlation is unclear presently. But if interpreted in the context of traditional risk factors it aids and helps people to get themselves motivated especially young individuals (1-4).


1.AETNA Number: 0228 Clinical Policy Bulletin: Cardiac CT, Coronary CT Angiography and Calcium Scoring

2.O'Malley PG. Rationale and design of the Prospective Army Coronary Calcium (PACC) Study

3.Rumberger JA, Sheedy PF, Breen JF, et al. Electron beam computed tomography and coronary artery disease: Scanning for coronary artery calcification. Mayo Clinic Proc. 1996;71:369-377.

4.Budoff MJ, Georgiou D, Brody A, et al. Ultrafast computed tomography as a diagnostic modality in the detection of coronary artery disease: A multicenter study. Circulation. 1996; 93:898-904

Conflict of Interest:

None declared

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Summary for Patients

Are Abnormal Lipid Levels Harmful in Young Adults?

The summary below is from the full report titled “Nonoptimal Lipids Commonly Present in Young Adults and Coronary Calcium Later in Life: The CARDIA (Coronary Artery Risk Development in Young Adults) Study.” It is in the 3 August 2010 issue of Annals of Internal Medicine (volume 153, pages 137-146). The authors are M.J. Pletcher, K. Bibbins-Domingo, K. Liu, S. Sidney, F. Lin, E. Vittinghoff, and S.B. Hulley.


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