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Am Heart J. 2014 Dec;168(6):878-83.e1. doi: 10.1016/j.ahj.2014.08.007. Epub 2014 Sep 16.

Long-term risk of cardiovascular events across a spectrum of adverse major plasma lipid combinations in the Framingham Heart Study.

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Framingham Heart Study, Framingham, MA; Boston University School of Medicine, Boston, MA.
Framingham Heart Study, Framingham, MA; Department of Mathematics and Statistics, Boston University, Boston, MA.
Framingham Heart Study, Framingham, MA; Section of Preventive Medicine and Cardiology, Boston University School of Medicine, Boston, MA.
Framingham Heart Study, Framingham, MA; Department of Biostatistics, Boston University School of Public Health, Boston, MA.



Blood levels of high low-density lipoprotein cholesterol (LDL-C), high triglycerides (TG), and low high-density lipoprotein cholesterol (HDL-C) have been associated with increased risk of cardiovascular disease (CVD). The long-term comparative CVD risk associated with these 3 major lipid classes in various combinations is, however, unknown.


A total of 3,501 participants of the Framingham Offspring Study (mean age 51 ± 10 years, 56% women) without CVD at baseline were followed up for incident CVD between 1987 and 2011. Participants were grouped according to baseline lipid values into 8 distinct categories to compare the prognostic significance of values within an optimal range to Third Report of the National Cholesterol Educational Program-defined high LDL-C (> 130 mg/dL), high TG (> 150 mg/dL), and/or low HDL-C (< 40 mg/dL) in various combinations using multivariable-adjusted Cox regression models.


On follow-up (median 20.2 years), 724 (21%) had new-onset CVD. Adjusted for confounders and compared with the group with optimal lipid values, hazards ratios and population-attributable risks (PARs) were as follows: isolated low HDL-C, 1.93 (95% CI 1.37-2.71), PAR = 3.1%; isolated high LDL-C, 1.28 (1.03-1.59), PAR 6.4%; isolated high TG, 1.35 (0.91-1.98), PAR = 1.1% (not significant); low HDL-C and high LDL-C, 1.82 (1.33-2.49), PAR = 3.9%; low HDL-C and high TG, 1.74 (1.28-2.37), PAR = 3.9%; high LDL-C and high TG, 1.52 (1.12-2.07), PAR = 6.4%; and high LDL-C, high TG and low HDL-C 2.28 (1.73-3.02), PAR = 7.5%.


Aside from isolated hypertriglyceridemia, low levels of HDL-C, high levels of LDL-C, and high levels of TG in any combination were associated with increased risk of CVD.

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