A new study by Harvard School of Public Health (HSPH) researchershas found that a subclass of high-density lipoprotein (HDL) cholesterol , the so-called "good" cholesterol, may not protect against coronary heart disease (CHD) and in fact may be harmful. This is the first study to show that a small protein,apolipoprotein C-III (apoC-III), that sometimes resides on thesurface of HDL cholesterol may increase the risk of heart disease and that HDL cholesterol without this protein may be especiallyheart protective. The study was published online in the Journal of the American Heart Association. "This finding, if confirmed in ongoing studies, could lead tobetter evaluation of risk of heart disease in individuals and tomore precise targeting of treatments to raise the protective HDL orlower the unfavorable HDL with apoC-III," said Frank Sacks,professor of cardiovascular disease prevention at HSPH and seniorauthor of the study. A high level of HDL cholesterol is strongly predictive of a lowincidence of coronary heart disease (CHD). |
But trials of drugs thatincrease HDL cholesterol have not consistently shown decreases inCHD, leading to the hypothesis that HDL cholesterol may containboth protective and non-protective components. ApoC-III, a proinflammatory protein, resides on the surface of somelipoproteins - both HDL and low-density lipoproteins, or LDL("bad") cholesterol. The researchers, led by Sacks and MajkenJensen, research associate in the Department of Nutrition at HSPH,examined whether the existence or absence of apoC-III on HDLcholesterol affected the "good" cholesterol's heart-protectivequalities, and whether its existence could differentiate HDLcholesterol into two subclasses - those which protect against therisk of future heart disease and those which do not. Blood samples collected in 1989 and 1990 from 32,826 women in theBrigham and Women's Hospital-based Nurses' Health Study wereexamined, along with blood samples collected from 1993 to 1995 from18,225 men in the Health Professionals Follow-up Study. During 10to 14 years of follow-up, 634 cases of coronary heart disease weredocumented and matched with controls for age, smoking, and date ofblood drawing.
The researchers compared plasma concentrations of total HDL, HDLthat has apoC-III, and HDL without apoC-III as predictors of therisk of CHD. After adjusting for age, smoking status and other dietary andlifestyle cardiovascular risk factors, the researchers found thattwo different subclasses of HDL have opposite associations with therisk of CHD in apparently healthy men and women. The major HDLtype, which lacks apoC-III, had the expected heart-protectiveassociation with CHD. But the small fraction (13%) of HDLcholesterol that has apoC-III present on its surface wasparadoxically associated with a higher, not lower, risk of futureCHD. Those men and women who had HDL apoC-III in the highest 20% ofthe population had a 60% increased risk of CHD.
The results suggest that measuring HDL apoC-III and HDL withoutapoC-III rather than the simpler measure of total HDL may be abetter gauge of heart disease risk (or of HDL's protectivecapacity). "Reduction in HDL-apoC-III by diet or drug treatmentsmay become an indicator of efficacy," said Jensen. Additional References Citations.
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