HIV, Dyslipidemia, and CVD Risk Sergio Fazio, MD, PhD Cornelius Vanderbilt Chair of Cardiovascular Medicine Professor of Medicine, Pathology, Immunology and Microbiology Chief, Section of CVD Preventio Vanderbilt University Medical Center Nashville, Tennessee
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HIV, Dyslipidemia, and CVD Risk · 2012-11-20 · HIV, Dyslipidemia, and CVD Risk Sergio Fazio, MD, PhD Cornelius Vanderbilt Chair of Cardiovascular Medicine Professor of Medicine,
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HIV, Dyslipidemia, and CVD Risk
Sergio Fazio, MD, PhD
Cornelius Vanderbilt Chair of Cardiovascular Medicine
Professor of Medicine, Pathology, Immunology and Microbiology
Chief, Section of CVD Preventio
Vanderbilt University Medical Center
Nashville, Tennessee
One Case
54-yo man with HIV, diabetes, HTN, and dyslipidemia
No CHD, no family history of CHD, no smoking
HIV: controlled onAtripla 600/200/300 and Isentress 400 mg twice
a day
HTN: controlled on HCTZ/ACE-I
T2D: poorly controlled on metformin 1000 plus glipizide 4
(HbA1c 9.3%)
LDL 83 mg/dl, on pravastatin 40 mg
TG 1770 mg/dl on fenofibrate 160 and fish oil supplement 2 g
Also on aspirin 81 mg
One Case
Stress test normal, CAC zero
Amylase and lipase normal
AST 114, ALT 151
Dietary instructions
Omega 3 supplement to 4g
Metformin to 2000 mg
Glipizide to 10 mg
At 3-month follow up, patient has lost 10 pounds
TG 330 mg/dl (LDL 94 mg/dl)
HbA1c 6.3%
AST 60, ALT 75
Another Case
64-yo man with HIV, diabetes, CAD (stent in LAD 8 years prior),
and dyslipidemia
HIV: controlled on Truvada 200/300 mg, Isentress 400 mg twice a
day, Intelence 100 mg Tab 2 tablets twice a day for 120 days
T2D: poorly controlled on glipizide 5 (HbA1c 9.0%)
Direct effects of the virus on the vasculature, increased CIMT
Effects of ARV drugs, lipodystrophy
Grinspoon et al. Circulation 2008;118(2):198-210.
HIV and Dyslipidemia
Untreated patients with HIV infection commonly show
Increased TC
Decreased LDL-C
Decreased HDL-C
Increased TG
Patients treated with ARV medications commonly show
Increased TC
Increased LDL-C
Decreased HDL-C
Increased TG
1. Feeney, Mallon. Open Cardiovasc Med J 2011;5:49-63.
2. Grinspoon et al. Circulation 2008;118(2):198-210.
3. United States Department of Veterans Affairs. http://www.hiv.va.gov/provider/manual-primary-
care/dyslipidemia.asp#S2X.
HIV and CHD Risk
Increased rates of CHD in HIV-infected patients on anti-
retrovirals
HIV-positive patients in the Kaiser-Permanente cohort
(N = 20,081) had significantly increased CHD risk
(p<.001) over HIV-negative control group
(N = 215,158)
DAD, a large, prospective, multicohort study
(N = 23,468) showed association between ARV therapy
and risk of MI
1. Feeney, Mallon. Open Cardiovasc Med J 2011;5:49-63.
2. Klein et al. Circulation 2012;125:A060.
3. Friis-Møller et al. New Engl J Med 2003; 349(21):1993-2003.
HAART and CVD Risk: Results
from the DAD Study
The highest prevalence of dyslipidemia was seen in regimens
containing drugs from both the PI and NNRTI classes,
suggesting a possible additive effect of combinations of drugs
from these drug classes
Dyslipidemia was most strongly correlated with current use of
ARV regimens, rather than a history of previous drug
regimens
There was a strong association between elevated total
cholesterol level and higher CD4+ cell counts, which was
present within each treatment category (PI, NNRTI,
NNRTI+PI) except the ARV-therapy-naïve group
Friis-Møller et al. AIDS 2003;17(8):1179-1193.
Abnormal Lipid Parameters in HIV Patients
Abnormalities in lipid parameters can be due
to
HIV
HIV Medications
Other Medications
Other Diseases
Other Factors
Genetic predisposition
Can Triglycerides Cause
Atherosclerosis?
Association between TG and CHD in populations is weaker than that between LDL and CHD
Trials with TG-lowering drugs have not produced definitive evidence
Severe hyperTG does not commonly cause CVD
TG accumulation is not a hallmark of atherosclerosis
Foam-cell Formation:
Cholesterol entry
Li and Glass. Nat Med 2002
Lipid Profile in Patients With Premature
Coronary Artery Disease
*P<0.005 as compared with control. †P<0.05 as compared with control.
Genest JJ Jr, et al. Circulation. 1992;85:2025-2033.
Men Women
Control
CAD
†
†
134
110
57
152
219
47
0
50
100
150
200
250
Pla
sm
a L
ipid
Co
nce
ntr
ati
on
, m
g/d
L
LDL-C TG HDL-C
*
*
138 141
45
139
177
35
LDL-C TG HDL-C 0
20
40
60
80
100
120
140
160
180
200
Pla
sm
a L
ipid
Co
ncen
trati
on
(m
g/d
L)
Recommended NCEP cutoff points
TG Levels and CHD Risk:
Meta-analysis of 29 Studies
N=262,525.
*Individuals in top versus bottom third of usual log-TG values, adjusted for at least age, sex, smoking status, lipid concentrations, and (in most studies) blood pressure.
Sarwar N, et al. Circulation. 2007;115:450-458.
≥10 years 5902
<10 years 4256
Adjusted for HDL
Yes 4469
No 5689
Groups CHD Cases
Overall CHD Risk Ratio*
Decreased
Risk
CHD Risk Ratio* (95% CI)
1.72 (95% CI, 1.56-1.90)
2 1 Increased
Risk
Sex
Male 7728
Female 1994
Nonfasting 2674
Fasting 7484 Fasting Status
Kuopio Study: Metabolic Syndrome and Mortality
Yes Metabolic Syndrome: No
CVD Mortality
0 2 4 6 8 10 12
0
5
10
15
20
RR (95% CI), 3.55 (1.96-6.43)
Follow-up, y
All-Cause Mortality
0 2 4 6 8 10 12
0
5
10
15
20 RR (95% CI), 2.43 (1.64-3.61)
Follow-up, y
RR = relative risk.
Lakka HM, et al. JAMA. 2002;288:2709-2716.
CV Risk Assessment
Advanced lipid testing
hsCRP and Lp-PLA2
cIMT
CAC
Long-Term Prognosis Associated with Absolute
Coronary Calcification and CAC Progression
n= 25,257
Budoff M, et al. J Am Coll Cardiol.
2007;49(18):1860-70. Epub 2007 Apr 20.
Follow-up (years)
Surv
ival P
roba
bilit
y
0.50
0.75
1.00
Non-Progressors
0 5 10 15 20
Progressors
Budoff M and Raggi P, submitted for pubblication
Lifestyle Changes
Diet (calories, nutrients, alcohol, supplements)
Weight management
Exercise
Smoking cessation
Central Adiposity in HIV is Associated with
Increased 5-year Mortality
Scherzer R, et al. AIDS. 2011; 25(11):1405-1414.
reference
1.77 (1.03, 3.03) P = 0.039
2.12 (1.13, 3.98) P = 0.019
Tertile 1
Tertile 2
Tertile 3
VAT: {
Odds ratio (95% CI)
0.10 1.00 10.00
Effects of a 6-month Lifestyle
Modification Program in HIV Pts
P = 0.008
mm
Hg
Systolic Blood Pressure
-20
-15
-10
-5
0
5
10
-4
-3
-2
-1
0
1
2
3
P = 0.022
cm
Waist Circumference
Control Lifestyle
Fitch KV, et al. AIDS. 2006;20(14):1843-1850.
Lipid-lowering Management Strategies
Lifestyle changes
Statins (plus ezetimibe
Fibrates
Omega 3 supplementation
Niacin
LaRosa JC et al. N Engl J Med. 2005;352.
0
30
5
10
15
20
25
Statin
Placebo
HPS
CARE
LIPID
HPS
CARE
LIPID
4S
4S
LDL cholesterol (mg/dL)
0 210 190 170 150 130 110 90 70
TNT (80 mg)
TNT (10 mg)
Event
(%)
Benefits of Intensive LDL-C Lowering
Coadministration of Statins with Protease Inhibitors