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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #233321
Title: Association of LDL subfractions with clinical cardiovascular outcomes: A systematic review

Author
item IP, STANLEY - TUFTS MEDICAL CENTER
item Lichtenstein, Alice
item CHUNG, MEI - TUFTS MEDICAL CENTER
item LAU, JOSEPH - TUFTS MEDICAL CENTER
item BALK, ETHAN - TUFTS MEDICAL CENTER

Submitted to: Annals of Internal Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2009
Publication Date: 4/7/2009
Citation: Ip, S., Lichtenstein, A.H., Chung, M., Lau, J., Balk, E.M. 2009. Association of LDL subfractions with clinical cardiovascular outcomes: A systematic review. Annals Of Internal Medicine. 150:474-484.

Interpretive Summary: LDL particles are positively associated with increased risk of heart disease. Different types of low-density lipoprotein (LDL), referred to as subfractions, have been associated with different degrees of risk. The objective of this review was to systematically evaluate the relationship between LDL subfractions, and incidence (rate of occurance) and progression (worsening) of heart disease. We identified and reviewed studies using the following computer searches, Medline, CAB Abstracts, and Cochrane Clinical Trial Registry, through June 2008, and only retrieved those published in English language. The study selection was limited to longitudinal designs (following people over a period of time) and which included at least 10 subjects. The data of interest was associations between LDL subfractions and incidence or severity of heart disease. The data from each study was extracted by one researcher and verified by another. Full data extraction including quality assessment was performed only for studies using assays for LDL subfractions available to clinical laboratories. These studies were graded as good, fair or poor quality. More limited data extraction was performed for assays for LDL subfractions available only in research laboratories. We found 23 research articles that met eligibility criteria; 9 used nuclear magnetic resonance and 1 used a clinically available gradient gel electrophoresis; 2 were good quality, 8 fair quality. 13 studies used other tests. Overall, 16 evaluated incident heart disease and 7 heart disease progression. Studies varied in their definitions of LDL subfractions, characteristics of study population, and measures of heart disease outcomes. Among studies evaluating clinically available tests, studies were varied in terms of whether any measures of LDL subfractions were associated with heart disease, which measures were associated with heart disease, and whether the associations persisted after controlling for lipoprotein cholesterol concentrations. Nuclear Magnetic Resonance measured particle concentration was generally associated with incident heart disease after adjustment for standard risk factors. Overall, 64% of analyses found statistically significant unadjusted associations with incident heart disease or progression, but only 48% of analyses were significant after adjustment. In conclusion, the evidence suggests that LDL subfractions may be associated with incidence and progression of heart disease, but it is unclear whether the associations are dependent of currently risk factors. The LDL subfraction methodology would benefit from a standardization protocol. Randomized trials are needed to prove the added value of these measures.

Technical Abstract: Context: Low-density lipoprotein (LDL) subfractions have been proposed as an independent risk factor for cardiovascular disease (CVD). Objective: Systematically review the relationship between LDL subfractions and incidence and progression of CVD. Data Sources: Medline, CAB Abstracts, and Cochrane Clinical Trial Registry through June 2008, limited to English language. Study Selection: Longitudinal design with 10 or more subjects reporting an association between LDL subfractions and incidence or severity of CVD. Data Extraction: Each study extracted by one researcher and verified by another. Full data extraction including quality assessment was performed only for studies using tests available to clinical laboratories. These studies were graded as good, fair, or poor quality. More limited data extraction was performed for tests available only in research laboratories. Results: 23 studies met eligibility criteria; 9 used nuclear magnetic resonance and 1 used a clinically available gradient gel electrophoresis;2 were good quality, 8 fair quality. 13 studies used other tests. Overall, 16 evaluated incident CVD and 7 CVD progression. Studies were highly heterogeneous in their definitions of LDL subfractions, populations, and CVD outcomes. Among studies evaluating clinically available tests, studies were heterogeneous in terms of whether any measures of LDL subfractions were associated with CVD, which measures were associated with CVD, and whether the associations persisted after controlling for lipoprotein cholesterol concentrations. However, NMR-measured particle concentration was generally associated with incident CVD after adjustment. Overall, 64% of analyses found statistically significant unadjusted associations with incident CVD or progression, but only 48% of analyses were significant after adjustment. Conclusions: The evidence suggests that LDL subfractions may be associated with incidence and progression of CVD, but it is unclear whether the associations are independent of currently used risk factors. The LDL subfraction methodology needs a standardization protocol. Randomized trials are needed to prove the added value of these measures.