the bad, proinflammatory HDL

Although the vast majority of epidemiol studies have found HDL to be cardioprotective, there have always been some concerns.  HDL is comprised of a diverse group of lipoproteins with significant metabolic heterogeneity.  there were a few older studies finding a "pro-inflammatory HDL", which predisposed people to heart disease (see my lipid powerpoint, slide 106, which cites small studies from 2003 and 2009). the clinical trial of Torcetrapib, a cholest ester transfer protein inhibitor, dramatically increased HDL but was not cardioprotective. the researchers suggested that the HDL was somehow deformed. (this large torcetrapib trial overwhelmed a meta-analysis last year in BMJ, suggesting no benefit to raising HDL). in any event, there is a likely very illuminating article from harv school pub health (see lipids inflam hdl apoC3 jaha 2012 in dropbox). they had found before that there was occasionally a small apolipoprotein (apo C-III) on some lipoproteins causing a pro-inflammatory and atherogenic response. on LDL particles, this apo C-III caused increased coronary athero independent of the LDL itself. they looked at the data from 2 large epidem studies -- Nurses health study (NHS, 121K female nurses) and the health professionals followup study (HPFS, 52K males), looked at stored serum and assessed the HDL C-III relation to cardiac events.  results:

. 14% of of women in NHS had HDL with apo C-III; 11% of men in HPFS had apo C-III
. Overall, each standard deviation increase in HDL was assoc with a 21% dec in cardiac events; but for patients without apo C-III, there was a 34% decrease in events and for those with apo C-III there was a statistically significant 18% increase.
. looking at the effect of apo C-III in multivariate analysis of other risk factors (all of below statistic signif):
           compared to pts with normal wt, overwt and obesity were assoc with 7% and 12% lower levels of HDL without apo C-III -- ie, overwt/obesity with lower of the good HDL.
            alcohol assoc with 3% higher levels of both HDL types
            smokers had 1% higher levels  of HDL with apo C-III (the bad one)
            premenopausal women had 9% higher levels of HDL without apo C-III, as did postmenop women on estrogen replacement therapy, vs other postmenop women.
            per SD increase in triglycerides,  8% lower HDL without apo C-III and 15% increase in HDL with apo C-III
            per SD increase in A1C, 4% increase in HDL with apo C-III
            
(ie, several of these risk factors which depress HDL also lead to more HDL with apo C-III)

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