KA Lichtenstein1, C Armon2, K Buchacz3, AC Moorman3, KC Wood2, JT Brooks3, and the HOPS Investigators

1
Analysis of Cardiovascular Risk Factors in the
HIV Outpatient Study (HOPS) Cohort
735
Kenneth A. Lichtenstein, MD University of
Colorado Health Sciences Center 4200 East 9th
Avenue, B163 Denver, Colorado, 80262 Kenneth.Licht
enstein_at_uchsc.edu P - 303-320-2830 F -
303-320-7016
KA Lichtenstein1, C Armon2, K Buchacz3, AC
Moorman3, KC Wood2, JT Brooks3, and the HOPS
Investigators 1University of Colorado Health
Sciences Center, Denver, CO 2Cerner Corporation,
Vienna, VA 3Centers for Disease Control and
Prevention, Atlanta, GA

• Background
• Lipid abnormalities and cardiovascular disease
  (CVD) in HIV-infected patients have led to
  concerns about the contribution of antiretroviral
  agents to these co-morbidities.
• Methods
• We analyzed a prospective, dynamic cohort of
  gt8,000 patients followed since 1993 in the HOPS.
  We used chi-square and logistic regression
  analyses to assess risk factors for
  cardiovascular events (myocardial infarction
  (MI), peripheral vascular disease (PVD), coronary
  artery disease (CAD) and stroke), including time
  on HAART after its initiation (took HAART gt95
  vs. lt95 of the time). We used Cox proportional
  hazards regression to assess the impact of
  treatment of hyperlipidemia on cardiovascular
  events.
• Study Population We included patients with
  visits from 3/1/1996 through 9/30/2005 who were
  either ARV-naïve or who had completely documented
  ARV histories, with at least 90 days of HAART
  experience. In addition, patients must have had
  at least one of each of the following tests
  total cholesterol, HDL, LDL, triglycerides, or
  glucose. We limited the Cox proportional hazards
  analysis of risk factors for CVD among patients
  with hyperlipidemia to the subset of patients
  diagnosed with hyperlipidemia during the
  observation period.
• Definitions Smoking indicated a current
  cigarette smoker at the time of entry into the
  HOPS. Diabetes was determined by diagnosis,
  treatment for diabetes, elevated hemoglobin A1C,
  or elevated fasting insulin or glucose levels
  (gtULN for all tests). Hypertension and
  hyperlipidemia were determined by clinician
  diagnosis of each condition.

• Results
• From 1993-2005, among 8,024 total patients
  followed in the HOPS, there were 57 MIs (Figure
  1a), 22 cases of PVD (Figure 1b), 86 cases of CAD
  (Figure 1c) and 22 cases of PVD (Figure 1d). MI
  cases peaked from 2000 and declined thereafter
  (Figure 1a) coincident with increased use of
  medications for hypertension and hyperlipidemia
  (Figure 2).
• 1,807 patients met inclusion criteria for
  this analysis, of whom 57 (3.2) contributed 84
  total CVD diagnoses 13 MI, 2 PVD, 57 CAD, and 12
  stroke diagnoses. Patients with CVD were older,
  and had a longer follow-up time than patients
  without CVD (Table 1).
• In the multivariate analysis (Figure 4),
  significant (plt0.05) independent risk factors for
  CVD were (adjusted odds ratio shown in
  parentheses) Age gt 40 years at pre-HAART CD4
  (3.31), diabetes (3.24), hyperlipidemia (1.95),
  and nadir HDL (0.97). Pre-HAART CD4 count,
  percent of time on HAART since start of first
  HAART regimen, BMIgt30, peak viral burden, peak
  total cholesterol, peak LDL, peak triglycerides,
  specific antiretroviral agents or classes (Table
  3), antiretroviral switches to other drugs or
  classes (Table 4), smoking, IDU, gender, or
  race/ethnicity were not statistically associated
  with CVD (data not shown).
• Use of lipid-lowering agents was associated
  with reduced risk for CVD among patients with
  hyperlipidemia (Table 5) (HR0.34, p0.02).
• Conclusions
• Among HOPS patients, the majority of whom are
  white and male, the risk of cardiovascular
  disease was associated with traditional CVD risk
  factors older age, preexisting hyperlipidemia,
  diabetes, and low nadir HDL.
• The risk of CVD was lowered with use of lipid
  lowering agents, but was unrelated to specific
  antiretroviral agents or changes in
  antiretroviral therapy.
• Acknowledgements
• The authors thank the staff and thousands of HOPS
  subjects across the United States for their
  continued support and participation in the study.

Table 2. Univariate Logistic Regression Analysis
of Risk Factors for CVD (N1807, CVD cases 57)
Table 1. Demographics of the Study Population
(N1807)
CVD Yes () No () (N 57) (N1750) CVD Yes () No () (N 57) (N1750)
Male gender 45 (78.9) 1399 (79.9)
Median Age 45 years 38 years
White race 36 (63.2) 1082 (61.8)
African-American 15 (26.3) 498 (28.5)
Hispanic 2 (3.5) 61(3.5)
Smoking (at HOPS entry) 26 (45.6) 675 (38.6)
Median follow-up 7.1 years 5.9 years
Effect Odds Ratiounadj 95 Confidence Interval p-value
Age gt 40 years 4.39 2.31-8.48 lt 0.001
Male gender 0.94 0.48-1.90 0.987
African American race 0.90 0.47-1.69 0.839
Hypertension 2.69 1.52-4.76 lt 0.001
Smoking (at HOPS entry) 1.34 0.76-2.34 0.349
Diabetes 5.32 2.73-10.3 lt 0.001
Nadir HDL lt 35 2.42 1.31-4.53 0.004
BMI gt 30 1.99 1.05-3.72 0.033
Hyperlipidemia 3.11 1.74-5.55 lt 0.001
Viral load gt 100K 1.61 0.96-2.71 0.076
HAART lt 95 1.39 0.77-2.50 0.303
Pre-HAART CD4 lt 200 1.67 0.95-2.92 0.076
IDU 2.03 0.82-4.78 0.098
Diagnoses 1 1 0 3
2 5 3 10 7 10
8 5 2 1
0 4 2 0 2 3
4 4 7 8 4 5
Patients seen (1070)(1949)(2530)(2742)(3062)(307
0)(3175)(3435)(3454)(3483)(3427)(3164) (2724)
(1061)(1935)(2519)(2746)(3043)(3048)
(3157)(3410)(3439)(3473) (3428)(3173)(2737)
Table 3 Antiretroviral use and CVD (N1807,
CVD cases 57)
Any use CVD No CVD p-value Any use CVD No CVD p-value
d4T, 40 mg. BID 32 (56) 853 (49) 0.33 NFV 21 (37) 693 (40) 0.78
d4T, lt 40 mg. BID 10 (18) 380 (22) 0.56 LPV/RTV 10 (18) 419 (24) 0.34
IDV 25 (44) 709 (41) 0.71 ATZ 4 (7) 253 (14) 0.16
RTV gt 800 mg./day 19 (33) 684 (39) 0.46 NVP 18 (32) 603 (34) 0.76
SQV 12 (21) 372 (21) 0.47 EFV 29 (51) 808 (46) 0.57
Table 4 Change in Antiretroviral use and CVD
(N1807, CVD cases 57)
Change from IDV, NFV, SQV, RTV, or LPV/RTV CVD No CVD p-value Change from IDV, NFV, SQV, RTV, or LPV/RTV CVD No CVD p-value
Change to ATZ 3 (5) 99 (6) 1.00 Change to any NNRTI 3 (5) 188 (11) 0.27
Diagnoses 0 0 1 1
7 2 6 10 8 12
9 10 20 0
0 0 0 1 1 0
1 0 3 7 6 3
Patients seen (1064)(1937)(2508)(2708)(3031)(302
1)(3132)(3382)(3413)(3442)(3394)(3140) (2719)
(1063)(1942)(2522)(2707)(3051) (3055)
(3165) (3417)(3446)(3479) (3436)(3177)(2737)
Table 5. Cox Proportional Hazards Analysis of
Risk Factors for CVD among Patients with
Hyperlipidemia (N363,
CVD cases 24)
Effect Hazard Ratioadj. 95 Confidence Interval p-value
Lipid-lowering agents 0.34 0.14-0.85 0.021
Age gt 40 years 2.38 0.88-6.43 0.087
Diabetes 2.45 0.99-6.05 0.052
Smoking 2.22 0.98-5.05 0.057

p lt 0.001 p lt 0.001 p
0.024 p 0.059 p 0.004
Time-dependent variable.
Patients Seen
Continuous variable Vertical bars 95
Confidence Intervals

The findings and conclusions from this
presentation are those of the authors and do not
necessarily represent the views of the Centers
for Disease Control and Prevention.