Title: DYSLIPIDEMIA AND ATHEROSCLEROSIS IN HIV INFECTION
1DYSLIPIDEMIA AND ATHEROSCLEROSIS IN HIV INFECTION
- MICHELLE FLORIS-MOORE, M.D., M.S.
- AIDS Research Program
- Dept. of Epidemiology Population Health
- Montefiore Medical Center
2BACKGROUND
- Pre-HAART Era
- HIV infection associated with high triglyceride
and low HDL levels. - Premature atherosclerosis described in
HIV-infected persons prior to introduction of
HAART. - Autopsy studies found arteriopathy, with
thickening of arterial intima and narrowing of
the lumen.
3HAART Era
- Fat redistribution, with peripheral/facial
wasting and central adiposity - May be predominantly LA or LH, or mixed LD
- Lipoatrophy most strongly associated with NRTI
use - Abnormal adipocytokine levels
- Leptin variably related to LD.
- Adiponectin levels lower in patients with LD.
Some studies show stronger association with LA
than with mixed LD. -
- Insulin resistance.
- Increased LDL and triglycerides.
4Leptin and Adiponectin
- Leptin
- secreted by adipocytes, also derived from other
sources (e.g. skeletal muscle) - Regulates food intake and energy expenditure
- deficiency ? insulin resistance
- Adiponectin
- Secreted exclusively by adipocytes
- Decreased levels associated with insulin
resistance, CVD.
5HIV and Carotid IMT
- Measured carotid IMT in Matched triads HIVve
HIVve, PI-naïve HIVve, on PI. - Matched on age, race, gender, BP, smoking,
menopausal status. - Excluded known CAD, DM, uncontrolled HTN, BMI gt
30, fam h/o MI. - No differences in carotid IMT among groups.
Traditional CAD risk factors assoc with ? IMT.
Currier J, et al (Abstract 131, CROI 2002)
6- Longitudinal study. HIVve vs HIV-ve. HIVves
grouped by ART use. - Carotid IMT measured at baseline and 1 yr.
- HIVve participants had
- (1) higher baseline carotid IMT
- (2) faster progression of IMT over 1 year
- PI use not associated with IMT.
Hsue P, et al. Circulation 20041091603-1608
7HIV and CAD outcomes
- DAD study prospective multicenter study,
23,468 participants. - ? total chol and TGs associated with length of
exposure to ART. - 126 MIs (36 fatal) from 1999 2002.
- Relative risk of MI 1.26 per year of HAART use.
Friis-Moller N, et al. AIDS 2003,
171179-1193 DAD Study Group. NEJM 2003, 349
1993-2003
8HIV and CAD outcomes
- Retrospective study of CAD events in 36,766 pts
at VA hospitals, 1995-2001. - Median length of HAART rx 16 mths.
- Outcome Hosp / death due to CAD / CVD.
- CAD/CVD hosp rate ?d (1.7/100py to 0.9).
- No association between ART and CAD/CVD.
Bozette S.A., et al. NEJM 2003 348702-710
9Objectives
- To describe the effect of HIV infection and
HAART on the lipid profile. - To examine the relationship of HIV infection and
HAART to body fat distribution and leptin and
adiponectin levels. - To describe the effects of HIV and HAART on rates
of sub-clinical atherosclerosis.
10Study Population
- Natural History of Menopause in HIV-Infected
Drug Users (MS) study. - Ongoing 5-year longitudinal study of menopause in
mid-life women who are either HIV-infected or at
risk for HIV infection. - Women aged 35 or older who have not yet completed
menopause transition.
11Metabolic Sub-study
- 240 women with no h/o MI
- Recruited into 4 groups
- HIV-uninfected
- HIV-infected, ART-naive
- HIV-infected, on non-PI HAART
- HIV-infected, on PI-based HAART
12Semi-annual Research Visit
- Interview Medical history, medications, dietary
intake, physical activity, drug and cigarette
use. - Measurements Weight, height, BP, waist and hip
circumference - Phlebotomy CD4 cell count, HIV Viral Load
13Outcome Measures
- Every 18 months, after a 12-hour overnight fast
Total cholesterol, HDL-C, LDL-C, Triglycerides,
Lipoprotein (a). - Fasting leptin, adiponectin, and FFA levels done
at baseline. - DEXA scans done at 18 month intervals to evaluate
body fat distribution. - Carotid artery ultrasound done to measure IMT at
baseline and in Year 3.
14Demographics
15Drug Use
16CD4 Count by ART group
p .40
17HIV-Infected Participants
18Duration of PI Use
19BMI Distribution
kg/m2
p lt .001
20Trunk and Limb Fat by HIV/ART Group
p .004
p .001
21Trunk/Limb Fat Ratio by HIV/ART Group
p .15
22Regional fat is lower in Cocaine UsersMS. n518
g/cm
g/cm
Trunk fat
Leg fat
23Leptin by HIV/ART group
p .02
24NHANES III Leptin Levels in Women by BMI and
Ethnicity
Ruhl CE, Everhart JE. Am J Clin Nutr
200174295-301.
25Adiponectin by HIV/ART group
p .71
26Factors Correlating with Leptin and Adiponectin
27Lipids by HIV/ART group
p .052
Median TG
28Lipids by CD4 Group
p lt .01
p .45
p .02
p .77
Median TG
29Lipids CD4 gt 500 group compared to HIV -ves
p lt .01
p lt .01
p .47
Median TG
30IGT and HTN by HIV/ART Group
p .68
p .34
Includes 15 women with pre-existing DM
31Carotid Artery IMT
- Common carotid artery IMT gt 0.8mm defined as
abnormal thickness. - 15 randomly selected studies read by second
radiologist for analysis of inter-rater
reliability. - Intra-class Correlation Coefficient 0.99 (95
CI 0.996 0.999)
32Mean IMT (mm) by Gender
33Percent with IMT gt 0.8mm by HIV/ART group
p .051
34Multivariate Analysis of IMT
35CONCLUSIONS
- HIV-infected participants on HAART had lower
trunk and limb fat mass compared to those not on
ART and to HIV-uninfected participants. - Leptin levels correlated positively with trunk
fat, limb fat, and HOMA-IR. - Adiponectin levels correlated negatively with
trunk fat, trunk/limb fat ratio, and HOMA-IR, and
positively with HDL levels.
36CONCLUSIONS
- Those in higher CD4 groups had higher levels of
total cholesterol and LDL cholesterol. - Traditional risk factors (age, obesity) and
current cocaine use were associated with
increased risk of pre-clinical atherosclerosis.
37ACKNOWLEDGEMENTS
- MS Study
- Ellie Schoenbaum
- Julia Arnsten
- Andrea Howard
- Yungtai Lo
- Nancy Budner
- Galina Moskaleva
- Mordecai Koenigsberg
- Renee Shanker
- Metta Cantlo
- Madeline Crespo-Figueroa
- Samantha Miller
- Tufts Nutrition Collaborative - CDAAR
- Alice Tang
- Jane Lanzillotti
- Lisa Gualtieri