Author + information
- John T. Wilkins, MD, MS∗ (, )
- Allan Sniderman, MD and
- Donald M. Lloyd-Jones, MD, ScM
- ↵∗Department of Preventive Medicine, Division of Medicine (Cardiology), Northwestern University Feinberg School of Medicine, 680 N. Lakeshore Drive, Suite 1400, Chicago, Illinois 60091
We appreciate the comments of Dr. Onat and colleagues. We also believe that the CARDIA (Coronary Artery Risk Development in Young Adults) study (1) adds substantially to the evidence that measurement of apolipoprotein B (apoB) concentration is a more accurate marker of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non—HDL-C) in young adults. Given that retention of apoB particles within the arterial wall is an essential step in the formation and maturation of atherosclerotic lesions (2), it makes sense that apoB would be an excellent marker of atherosclerotic cardiovascular disease risk because the number of atherogenic particles within the lumen of the artery should be a major determinant of the number of atherogenic apoB particles that become retained within the arterial wall. We agree that the heterogeneity of coronary artery calcification scores across discordant groups could be interpreted to support research that suggests complex and multifactorial processes involving inflammation and oxidation that lead to the initiation and maturation of atherosclerotic plaque. ApoB itself can be proatherogenic and proangiogenic within the arterial wall (3,4). As Dr. Onat and colleagues point out, risk factors tend to cluster and pathogenic processes multiply. Subjects with increased numbers of cholesterol-depleted LDL particles tend to be more obese and more frequently dysglycemic and hypertensive than normal subjects.
But in our analysis of the CARDIA cohort, it was the values of the markers at age 25 to the risk of coronary calcification at age 50 that were evaluated. At age 25, body mass index, systolic blood pressure, diastolic blood pressure, fasting glucose, and plasma triglycerides were all normal in the participants in the high apoB/low non—HDL-C and the high apoB/low LDL-C discordant groups. HyperapoB was present before the onset of obesity, dysglycemia, and hypertension in many participants. Thus, in some CARDIA participants, elevated apoB in early adulthood was the only marker that suggested a higher risk for subclinical atherosclerosis. Likewise, CARDIA also establishes that apoB is elevated in participants with cholesterol-depleted particles before triglycerides are elevated, which suggests that increased secretion of cholesterol-depleted apoB particles may be the primary abnormality in this syndrome. This is an important observation and requires further investigation.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
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