High-density Lipoprotein Particles but Not Low-density Lipoprotein Particles Predict Cardiovascular Disease Events in HIV Patients: Strategies for Management of ART Study
Daniel Duprez and INSIGHT/SMART Group
Univ of Minnesota, Minneapolis, US
Background: Intermittent use of ART (DC group) was
associated with an increased risk of serious cardiovascular disease (CVD)
compared to continuous ART (VS group) in the SMART Study. We previously
reported that high-density lipoprotein cholesterol (HDL-c) declined
significantly more in DC than VS patients at 12 months and this unfavorable
lipid change could offer a possible explanation for the increased risk of CVD. To
explore this finding further, lipoprotein particle concentrations were measured
in a random sample of DC and VS patients and for CVD cases and matched controls.
Studies in the general population have shown that low density particles
(LDL-p), particularly small LDL-p, and HDL-p predict CVD.
Methods: Lipoprotein particle concentrations were measured
in stored plasma from a random sample of 451 patients by nuclear magnetic
resonance at baseline and 1 month (218 DC and 233 VS). In addition, lipoprotein
particles at baseline were measured in 249 cases of CVD through study closure
on July 11, 2007 and in 494 controls matched for age, sex, country, and date of
randomization odds ratios (OR) (upper vs lowest quartile) of HDL-p, LDL-p, and
VLDL-p were estimated using conditional logistic regression with and without
adjustment for baseline age, race, ART, HIV RNA, CD4+ count,
smoking, prior CVD, diabetes, blood pressure and lipid-lowering drugs, body
mass index, hepatitis B or C co-infection, ECG abnormalities, LDL-c (or HDL-c
when studying LDL-p), and triglycerides.
Results: Average DC-VS differences for change after
1 month µmol/L were 2.3 (p <0.0001) for total HDL-p, 0.27 for large
HDL-p (p = 0.19), 1.1 (p = 0.003) for medium HDL-p, and 1.0 (p
= 0.02) for small HDL-p. Unadjusted OR of CVD were 0.40 (95%CI 0.26 to 0.63, p
= <0.0001) for total HDL-p (lower values associated with increased risk),
0.66 (0.44 to 1.05, p = 0.08) for large HDL-p, 0.91 (0.60 to 1.38, p
= 0.66) for medium HDL-p, and 0.53 (0.34 to 0.83, p = 0.005) for small
HDL-p. Adjustment did not alter the strength of the HDL-p associations. VLDL-p and
LDL-p concentrations were not significantly associated with CVD. Unadjusted and
adjusted OR for small LDL-p were 1.38 (0.87 to 2.19, p = 0.17) and 1.09
(0.56 to 2.13, p = 0.79).
Conclusions: Treatment interruption has a rapid
unfavorable effect on HDL particle concentrations. HDL-p in contrast to LDL-p concentrations
were significantly related to risk of CVD independent of other risk factors.