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HIV, Cocaine Use, and Hepatitis C Virus

A Triad of Nontraditional Risk Factors for Subclinical Cardiovascular Disease
Originally publishedhttps://doi.org/10.1161/ATVBAHA.116.307985Arteriosclerosis, Thrombosis, and Vascular Biology. 2016;36:2100–2107

Abstract

Objective—

We assessed cross-sectional and longitudinal associations of 3 nontraditional cardiovascular disease risk factors—HIV, cocaine use, and chronic hepatitis C virus infection—with 3 validated markers of subclinical cardiovascular disease: carotid artery plaque, albuminuria, and aortic pulse wave velocity in a well-characterized cohort.

Approach and Results—

We measured carotid plaque at baseline and after 24 months, urine albumin/creatinine ratio every 6 months, and pulse wave velocity annually for up to 36 months in a predominantly black cohort of 292 participants (100 HIV negative and 192 HIV positive). Thirty-nine percent had chronic hepatitis C virus infection and 20%, 28%, and 52% were never, past, and current cocaine users, respectively. Sixteen percent, 47%, and 64% of those with none, 1 or 2, or all 3 nontraditional risk factors had ≥2 abnormal cardiovascular disease risk markers (P=0.001). In fully adjusted models that included all 3 nontraditional risk factors, HIV infection was independently associated with carotid plaque progression (increase in the number of anatomic segments with plaque), albuminuria (albumin–creatinine ratio >30 mg/g), albuminuria progression (doubling of albumin–creatinine ratio from baseline to a value >30 mg/g), and pulse wave velocity. Cocaine use was associated with an ≈3-fold higher odds of carotid plaque at baseline, and hepatitis C virus infection was significantly associated with a higher risk of carotid plaque progression.

Conclusions—

These results suggest that HIV infection, cocaine use, and hepatitis C virus infection are important nontraditional risk factors for cardiovascular disease and highlight the need to understand the distinct and overlapping mechanisms of the associations.

Introduction

HIV, cocaine use, and hepatitis C virus (HCV) are overlapping epidemics in many US cities. Individually, each of these nontraditional risk factors has been implicated in cardiovascular disease (CVD)113 although with reports of null associations as well.1416 As combination antiretroviral therapy has substantially prolonged the life expectancy of HIV-infected patients, it is important to understand the traditional and nontraditional determinants of age-related comorbidities such as CVD. Few studies have rigorously assessed all 3 factors in a single population.

Using data from a longitudinal cohort, we sought to explore the independent associations of HIV, cocaine use (biologically validated), and active HCV (detectable HCV RNA) with cross-sectional and longitudinal trajectories of well-validated markers of subclinical CVD that predict CVD risk. We used ultrasonography to assess intima-media thickness (IMT) of the right common and internal carotid arteries and carotid plaque in all extracranial carotid artery segments. These carotid arterial measures are associated with the risk of future CVD events1719 and with CVD risk reduction in response to interventions such as use of lipid and blood pressure–lowering medications.20 Our second measure, albuminuria (urine albumin/creatinine ratio >30 mg/g), a component of chronic kidney disease,21 is thought to reflect systemic endothelial dysfunction22,23 and is a strong predictor of CVD events.24 Finally, we measured aortic pulse wave velocity (PWV), a measure of arterial stiffness that is an independent predictor of CVD events in a variety of populations.25

Materials and Methods

Materials and Methods are available in the online-only Data Supplement.

Results

A total of 292 participants completed at least 1 study visit and were included in the analysis (100 HIV negative and 192 HIV positive). The median (25th percentile [P25], 75th percentile [P75]) follow-up was 37 months (36, 37). The median (P25, P75) enrollment and last follow-up months were July 2011 (February 2011, February 2012) and August 2014 (March 2014, March 2015), respectively. Compared with HIV-negative participants, HIV-positive participants were more likely to be women, have a diagnosis of hypertension, be taking antihypertensive and antilipidemic medication, have a history of cocaine use, and have HCV infection (Table 1). Age, race, smoking status, body mass index, total/high-density lipoprotein cholesterol ratios, estimated glomerular filtration rate, and American College of Cardiology/American Heart Association (ACC/AHA) CVD risk scores26 were similar in the 2 groups.

Table 1. Baseline Characteristics of 292 Study Participants According HIV Status, Baltimore, MD

CharacteristicHIV Negative(n=100)HIV Positive(n=192)P Value
Women, n (%)19 (19)67 (35)0.005
Age, y, median (P25, P75)49 (45, 54)49 (45, 53)0.59
Black, n (%)92 (92)181 (94)0.46
Smoking status, n (%)0.80
 Never27 (27)46 (24)
 Past12 (12)22 (11)
 Current61 (61)124 (65)
Hypertension, n (%)21 (21)67 (35)0.016
Taking antihypertensive medication, n (%)19 (19)63 (33)0.014
Systolic blood pressure, mm Hg, median (P25, P75)126 (113, 135)119 (108, 131)0.007
Body mass index, kg/m2, median (P25, P75)27 (23, 33)25 (23, 31)0.15
eGFR*, mL/min per 1.73 m2, median (P25, P75)103 (91, 114)103 (84, 118)0.74
 ≥90, n (%)76 (76)131 (68)0.10
 60–89, n (%)24 (24)54 (28)
 <60, n (%)07 (4)
Total/HDL cholesterol ratio, median (P25, P75)3.1 (2.4, 4.1)3.1 (2.5, 4.2)0.87
Using statins, n (%)4 (4)27 (14)0.008
Self-reported history of CVD, n (%)4 (4)21 (11)0.05
ACC/AHA CVD risk score, median (P25, P75)6.1 (3.6, 9.8)5.2 (2.2, 9.0)0.095
Cocaine use§, n (%)0.002
 Never31 (31)26 (14)
 Past24 (24)58 (30)
 Current45 (45)108 (56)
Active hepatitis C virus, n (%)23 (23)92 (48)<0.001
Time since enrollment in HIV clinic, years, median (P25, P75)8.1 (3.5, 12.2)
History of AIDS-defining condition, n (%)48 (25)
Nadir CD4 cell count, cells/mm3, median (P25, P75)146 (43, 302)
Taking antiretroviral therapy, n (%)175 (91)
 Ritonavir-boosted protease inhibitor, n (%)127 (66)
 Nonnucleoside reverse transcriptase inhibitor, n (%)47 (24)
 Integrase strand transfer inhibitor, n (%)40 (21)
 Tenofovir, n (%)130 (68)
 Abacavir, n (%)30 (16)
Current CD4 cell count, cells/mm3, median (P25, P75)467 (248, 627)
HIV RNA <400 copies/mL, n (%)152 (79)
No. of study visits completed, median (P25, P75)6 (5, 7)6 (6, 7)0.005

ACC/AHA indicates American College of Cardiology/American Heart Association; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; and P25, P75, 25th percentile, 75th percentile.

*Glomerular filtration rate estimated with serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation.

Twenty-five participants reported ≥1 previous CVD events at baseline including (1) heart attack (n=5), open heart surgery for blocked blood vessels (n=2), balloon treatment or stent placed in heart (n=1), or stroke or ministroke (n=21).

ACC/AHA CVD risk score25 is the predicted 10-year risk of CVD derived from an equation that includes age, sex, race, total cholesterol, HDL cholesterol, diabetes mellitus, systolic blood pressure, smoking status, and use of antihypertensive medication. Point estimates are expressed per 5 percentage point increase in the risk score.

§Cocaine use categorized for each participant on the basis of self-report and urine drug tests obtained during the course of study observation (see text for details).

We categorized cocaine use status for each participant on the basis of all self-report and urine drug test data collected during follow-up: (1) never users denied historical and recent (previous 6 months) cocaine use at all visits and had all negative urine cocaine tests; (2) past users reported previous cocaine use at the baseline survey, but denied recent use in all surveys and had all negative urine cocaine tests; (3) current users either reported recent cocaine use or had cocaine detected by urine drug test at ≥1 visits. Urine drug test data led to substantial reclassification of cocaine use compared with self-report alone; of 85 participants categorized as never users and 136 categorized as past users by self-reported data, 28 (33%) and 54 (40%), respectively, were recategorized as current users on the basis of cocaine detection in at least 1 drug test. Consequentially, 57 participants were categorized as never cocaine users, 82 as past users, and 153 as current users (Table 1). Among participants categorized as current cocaine users during the study period, recent cocaine use (either by self-report [past 6 months] or urine drug test) was detected at median (P25, P75) of 57% (33%, 100%) of study visits. Baseline participant characteristics stratified by cocaine use status are shown in Table I in the online-only Data Supplement.

Correlations among subclinical CVD markers were modest, with Spearman ρ values of 0.13, 0.17, and 0.19 for albumin/creatinine ratio versus carotid IMT, PWV versus IMT, and albumin/creatinine ratio versus PWV, respectively (P<0.05 for all comparisons). Considering the sum of nontraditional risk factors at the individual level, we found evidence that having more risk factors (HIV, cocaine use [past or current], and HCV) was associated with having a larger number of abnormal subclinical CVD markers (carotid plaque, albuminuria, and PWV >9.6 m/s at any visit; Figure; P=0.001 for overall difference).

Figure.

Figure. Bar chart showing percentages of participants with 0, 1, 2, or 3 cardiovascular disease (CVD) indicators (carotid plaque, albuminuria, and pulse wave velocity >9.6 m/s measured at any visit) according to the number of nontraditional risk factors (HIV, cocaine use [past or current], and hepatitis C virus). The figure includes 276 participants (95%) with at least 1 valid measure of each CVD indicator). The percentages with 0, 1, 2, and 3 cardiovascular indicators were 20%, 63%, 13%, and 3% in those with no nontraditional risk factors; 22%, 32%, 32%, and 15% in those with 1 or 2 nontraditional risk factors; and 14%, 22%, 43%, and 21% in those with all 3 nontraditional risk factors (P=0.001 for overall difference).

A total of 279 participants (96%) had technically adequate carotid assessments at baseline, and of these, 221 completed technically adequate assessments at 24 months. One hundred forty-nine (53%) participants had carotid plaque detected at baseline. Plaque progression was defined as the presence of plaque in a larger number of the 12 anatomic segments at the 24-month assessment compared with the baseline assessment. Of participants with repeat imaging at 24 months, plaque progression was detected in 47 (40%) and 20 (20%) of those with and without plaque at baseline, respectively. (P=0.002 for difference). Two participants had clinically significant carotid stenosis, on the basis of visual stenosis of >50% with peak blood flow velocity of >160 cm/s. Both past and current cocaine use had strong independent associations with the presence of carotid plaque at baseline in a model that included all 3 nontraditional risk factors and ACC/AHA CVD risk scores (Table 2). Past cocaine use, HIV-positive status, and HCV-positive status had significant unadjusted associations with plaque progression at 24 months although only HIV and HCV status remained significantly associated with plaque progression in the fully adjusted model. In a supplemental modeling approach using individual components of the ACC/AHA CVD risk score, rather than using the risk score itself, results were similar; however, HCV status no longer was significantly associated with plaque progression (odds ratio, 1.8 [0.9, 3.5]; Table II in the online-only Data Supplement). In contrast, neither HIV, cocaine use, nor HCV had significant associations with baseline carotid IMT or with subsequent change in IMT (Table 2).

Table 2. Associations of HIV, Cocaine Use, and Hepatitis C With Carotid Artery Plaque and Intima-Media Thickness Among 279 Participants, Baltimore, MD

Presence of Carotid Plaque at BaselineCarotid Plaque Progression
Risk FactorFrequency (%)Unadjusted OR(95% CI)Adjusted* OR(95% CI)Frequency (%)Unadjusted OR(95% CI)Adjusted* OR(95% CI)
Cocaine use
 Never (n=55)16 (29)Ref.Ref.9 (20)Ref.Ref.
 Past (n=78)49 (63)4.1 (2.0 to 8.6)3.3 (1.5 to 7.3)27 (42)2.9 (1.2 to 7.1)1.9 (0.8 to 4.9)
 Current (n=146)84 (58)3.3 (1.7 to 6.4)2.7 (1.3 to 5.5)31 (28)1.5 (0.7 to 3.5)1.0 (0.4 to 2.4)
HIV status
 Negative (n=96)79 (43)Ref.Ref.14 (20)Ref.Ref.
 Positive (n=183)107 (57)1.5 (0.9 to 2.5)1.4 (0.8 to 2.5)53 (35)2.2 (1.1 to 4.4)2.1 (1.0 to 4.3)
Hepatitis C status
 Negative (n=169)83 (49)Ref.Ref.32 (24)Ref.Ref.
 Positive (n=110)66 (60)1.6 (1.0 to 2.5)1.0 (0.6 to 1.8)35 (41)2.3 (1.3 to 4.1)1.9 (1.0 to 3.6)
CVD risk score§1.8 (1.4 to 2.4)1.3 (1.0 to 1.8)
Carotid IMT at Baseline, µmAnnualized Change in Carotid IMT, µm/y
Mean±SDUnadjusted Difference(95% CI)Adjusted* Difference(95% CI)Mean±SDUnadjusted Difference(95% CI)Adjusted* Difference(95% CI)
Cocaine use
 Never (n=55)788±259Ref.Ref.16±58Ref.Ref.
 Past (n=78)852±24364 (−26 to 154)30 (−60 to 121)16±52−1 (−23 to 22)−10 (−33 to 13)
 Current (n=146)852±26864 (−17 to 145)32 (−51 to 11)14±63−2 (−23 to 18)−12 (−33 to 10)
HIV status
 Negative (n=96)841±224Ref.Ref.13±43Ref.Ref.
 Positive (n=183)839±277−2 (−67 to 62)3 (−62 to 68)16±654 (−13 to 20)5 (−12 to 22)
Hepatitis C status
 Negative (n=169)825±268Ref.Ref.9±61Ref.Ref.
 Positive (n=110)862±24638 (−25 to 99)15 (−49 to 79)24±5515 (−1 to 31)14 (−2 to 31)
CVD risk score§76 (47 to 105)2 (1 to 4)

CI indicates confidence interval; CVD, cardiovascular disease; IMT, intima-media thickness; OR, odds ratio; and ref., reference group.

*Adjusted models include all variables shown.

P<0.001.

P<0.05 and P≥0.001.

§American College of Cardiology/American Heart Association CVD risk score25 is the predicted 10-year risk of CVD derived from an equation that includes age, sex, race, total cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, systolic blood pressure, smoking status, and use of antihypertensive medication. Point estimates are expressed per 5 percentage point increase in the risk score.

Forty-three participants (15%) had albuminuria at baseline, and albuminuria progression—defined as a urine albumin/creatinine ratio during follow-up that was >30 mg/g and at least 2-fold higher than the baseline value—was detected in 14 (33%) and 57 (23%) of those with and without albuminuria at baseline, respectively (P=0.18 for difference). HIV-positive status was independently associated with an increased risk of both baseline albuminuria and with albuminuria progression, whereas cocaine use categories and HCV had no significant associations with albuminuria or albuminuria progression in models that included all 3 nontraditional risk factors and ACC/AHA CVD risk scores (Table 3). In a supplemental modeling approach using individual components of the ACC/AHA CVD risk score, rather than using the score itself, results were similar; however, HIV status no longer was significantly associated with baseline albuminuria (odds ratio, 1.8 [0.7, 4.4]; Table III in the online-only Data Supplement). HIV did remain significantly associated with albuminuria progression in the supplemental model.

Table 3. Associations of Cocaine Use, HIV, and Hepatitis C With Baseline Albuminuria and Albuminuria Progression Among 292 Participants, Baltimore, MD

Risk FactorPresence of Albuminuria at BaselineAlbuminuria Progression
Frequency (%)Unadjusted OR (95% CI)Adjusted* OR (95% CI)Frequency (%)Unadjusted OR (95% CI)Adjusted* OR (95% CI)
Cocaine use
 Never (n=57)5 (9)Ref.Ref.11 (19)Ref.Ref.
 Past (n=82)15 (18)2.3 (0.8–6.8)1.7 (0.6–5.2)16 (20)1.0 (0.4–2.4)0.7 (0.3–1.7)
 Current (n=153)23 (15)1.8 (0.7–5.1)1.3 (0.5–3.9)44 (29)1.7 (0.8–3.6)1.2 (0.5–2.6)
HIV status
 Negative (n=100)8 (8)Ref.Ref.14 (14)Ref.Ref.
 Positive (n=192)35 (18)2.6 (1.1–5.8)2.4 (1.0–5.6)57 (30)2.6 (1.4–4.9)2.5 (1.3–4.8)
Hepatitis C status
 Negative (n=177)22 (12)Ref.Ref.36 (20)Ref.Ref.
 Positive (n=115)21 (18)1.6 (0.8–3.0)1.2 (0.6–2.4)35 (30)1.7 (1.0–2.9)1.4 (0.8–2.5)
CVD risk score1.2 (0.9–1.6)1.1 (0.8–1.4)

CI indicates confidence interval; CVD, cardiovascular disease; OR, odds ratio; and ref., reference group.

*Adjusted models include all variables shown.

P<0.05

American College of Cardiology/American Heart Association CVD risk score25 is the predicted 10-year risk of CVD derived from an equation that includes age, sex, race, total cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, systolic blood pressure, smoking status, and use of antihypertensive medication. Point estimates are expressed per 5 percentage point increase in the risk score.

During the course of follow-up, 288 participants (99%) underwent 975 technically adequate PWV measurements in 1038 study visits (94%), with a median (P25, P75) of 4 (3, 4) measures per participant. The median (P25, P75) PWV at baseline was 8.2 m/s (7.1, 9.6). In a model accounting for correlations in repeated measures from individual participants and adjusted for all 3 nontraditional risk factors and ACC/AHA CVD risk scores, we found that HIV-positive status was significantly associated with higher PWV, whereas HCV was not associated with PWV (Table 4). Unexpectedly, we found that cocaine use (both past and current) was associated with lower PWV values; for current cocaine users, this association was statistically significant in the fully adjusted model (−57 cm/s versus never users; 95% confidence interval, −107 to −7). In a supplemental modeling approach using individual components of the ACC/AHA CVD risk score, rather than using the score itself, current cocaine use was not significantly associated with PWV (Table IV in the online-only Data Supplement). A total of 137 participants (48%) with ≥1 valid PWV measures had at least 1 value of >9.6 m/s. Analysis of PWV as a binary variable at this cutoff produced similar results to the analysis of PWV as a continuous variable (data not shown).

Table 4. Associations of HIV, Cocaine Use, and Hepatitis C With Aortic Pulse Wave Velocity Among 288 Participants, Baltimore, MD

Risk FactorUnadjusted Difference, cm/s(95% CI)Adjusted* Difference, cm/s(95% CI)
Cocaine use
 NeverRef.Ref.
 Past0 (−55 to 55)−37 (−92 to 18)
 Current−21 (−70 to 28)−57 (−107 to −7)
HIV status
 NegativeRef.Ref.
 Positive31 (−8 to 70)45 (6 to 84)
Hepatitis C status
 NegativeRef.Ref.
 Positive26 (−12 to 64)20 (−17 to 57)
CVD risk score46 (28 to 64)§

CI indicates confidence interval; CVD, cardiovascular disease; and ref., reference group.

*Adjusted model includes all variables shown.

P<0.05 and P≥0.001.

American College of Cardiology/American Heart Association CVD risk score25 is the predicted 10-year risk of CVD derived from an equation that includes age, sex, race, total cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, systolic blood pressure, smoking status, and use of antihypertensive medication. Point estimates are expressed per 5 percentage point increase in the risk score.

§P<0.001.

To further explore these findings, we assessed systolic blood pressure at the time of PWV measurements. As anticipated, blood pressure was positively correlated with PWV, with each 10 mm Hg increase in mean arterial blood pressure associated with a 55 cm/s (95% confidence interval, 44–65; P<0.001) increase in PWV. However, there were no associations of cocaine use or HCV status with mean arterial blood pressure (data not shown). HIV-positive participants had significantly lower adjusted mean arterial blood pressure when compared with HIV-negative participants (adjusted difference, −4 mm Hg; 95% confidence interval, −6 to −1). There was no evidence of effect modification among HIV infection, cocaine use, and HCV infection with any of the subclinical CVD markers assessed. Average outcome measurement data by study visit are shown in Table V in the online-only Data Supplement.

Discussion

In this unique longitudinal study, we found evidence that HIV infection, cocaine use, and HCV infection were independently associated with subclinical CVD in a sample of middle-aged, predominantly black individuals. In adjusted models, HIV disease was independently associated with carotid plaque progression, albuminuria, albuminuria progression, and PWV. Cocaine use was associated with an ≈3-fold higher odds of carotid plaque at baseline, and HCV infection was significantly associated with a higher risk of carotid plaque progression. In analyses of longitudinal changes in subclinical CVD markers, we did not find evidence that current cocaine use affected indicator trajectories differently than past cocaine use.

Our finding should be interpreted in light of the study’s strengths and weaknesses. Strengths include a longitudinal design, high follow-up rates, and 3 well-validated measures of subclinical CVD. The markers of interest—carotid plaque/IMT, albuminuria, and PWV—were modestly correlated with one another although each was strongly associated with ACC/AHA CVD risk score, suggesting that these different markers may capture different aspects of CVD. Additional study strengths include characterization of HCV status on the basis of detectable viremia and use of urine toxicology to validate self-reported cocaine use. Urine drug testing led to reclassification of 33% and 40% of self-reported never users and past users, respectively, to current user status. Study weaknesses include a relatively small sample size and only 3 years of longitudinal follow-up. Our study participants were predominantly black, reflecting local demographics, and our findings may not extrapolate to other racial groups.

Among the nontraditional risk factors assessed, we found the most consistent evidence for an association between HIV status and subclinical CVD. In our study, HIV status had independent associations with all 3 subclinical CVD markers. This finding accords with studies linking HIV infection to an increased risk for CVD events8,11,12 and to a higher prevalence of subclinical CVD markers.1,2,4,9 Although the mechanism underlying the association of HIV infection with CVD risk is incompletely elucidated, a high prevalence of traditional CVD risk factors in the population, adverse effects of antiretroviral drugs,27 inflammation, and immune activation have all been posited as contributing factors.28,29

We found that cocaine use (both past and current) was strongly associated with the presence of carotid plaque at baseline and with plaque progression in the unadjusted model although not in the fully adjusted model. This finding supports data from Lai et al,30,31 who found strong associations among chronic cocaine use, coronary calcium, and coronary plaque among black participants. The acute sympathomimetic effects of cocaine use, including myocardial infarction, are well characterized,32 but evidence also suggests chronic irreversible vascular damage from cocaine use.33,34

A unique aspect of our study was the ability to distinguish past and current cocaine users with biological validation. We did not, however, find evidence of more rapid progression of CVD surrogates in current versus past users. In fact, point estimates for these 2 groups, relative to never users, were similar in most analyses. Similarly, 1 small study that used contingency management to reduce cocaine use in chronic users found that cocaine abstinence was associated with significantly reduced serum endothelin-1 concentrations, but not with the incidence of coronary plaque progression.35 These data imply that cocaine use may initiate a trajectory of CVD that, at some point, progresses independently of continued cocaine use. It should also be noted that our ability to distinguish small longitudinal differences in past and current cocaine users was limited by relatively short follow-up.

Unexpectedly, we found a protective association between current cocaine use and PWV. This finding may be spurious, as the association was nonsignificant in univariate analysis, but became statistically significant in the adjusted model. Moreover, the association of current cocaine use with PVW was not statistically significant in a supplemental modeling approach where we adjusted models for individual components of the ACC/AHA CVD risk, rather than for the risk score itself. One small Australian study found cocaine use to be associated with increased aortic PWV.36 That study measured PWV with cardiac and aortic magnetic resonance imaging, and we used applanation tonometry for PWV measurement, limiting the ability to make direct comparisons.

The evidence of an independent association between HCV and subclinical CVD was relatively weaker than the associations of HIV and cocaine use with CVD. Although, HCV had moderate associations with several CVD indicators in univariate analyses, HCV retained statistical significance only with carotid plaque progression in multivariate analysis. This association did not retain statistical significance in a supplemental modeling approach although the point estimate was similar to that in the primary analysis. An important caveat is that our study was not sufficiently powered to assess modest associations between HCV and subclinical CVD, consistent with the effect sizes reported in large observational studies.3,7,37 However, our study highlights the importance of considering drug use and other behavioral factors as confounders of the observed relationship between HCV and CVD, factors that may be difficult to characterize in administrative databases.

A final consideration is the incongruity between associations assessed with carotid plaque and those assessed with carotid IMT. HIV infection, cocaine use, and HCV infection all had significant independent associations with carotid plaque, but none had significant associations with carotid IMT or change in IMT, and most point estimates approximated the null. Of note, our plaque assessments included the common, bifurcation, and internal carotid artery segments on both the right and left, whereas IMT measurements were acquired only in the right carotid artery. However, there has also been substantial variability in the findings across studies focused on HIV and HCV associations with carotid IMT.28,38 Different imaging protocols may account for some inconsistencies, and 1 study suggested that HIV- and inflammation-related progression of carotid disease may be more marked at the carotid bifurcation than in the common or internal carotid arteries, because of lower shear stress at the bifurcation.39 Indeed, carotid plaque is more prevalent at the bifurcation and internal carotid than in the common carotid,39 as we observed. Carotid plaque consistently has been shown to be a better predictor of future CVD events than of carotid IMT.19,40

This study assessed independent associations of HIV infection, cocaine use, and HCV infection with validated surrogate CVD markers. We found HIV infection to be independently associated with carotid plaque progression, albuminuria, albuminuria progression, and PWV, whereas cocaine use was associated with carotid plaque at baseline, and HCV was associated with carotid plaque progression. These results suggest that HIV, cocaine use, and HCV are important nontraditional risk factors for CVD in some populations and highlight the need to understand the distinct and overlapping mechanisms of the associations.

Nonstandard Abbreviations and Acronyms

ACC/AHA

American College of Cardiology/American Heart Association

CVD

cardiovascular disease

HCV

hepatitis C virus

IMT

intima-media thickness

PWV

pulse wave velocity

Acknowledgments

We want to thank the study participants.

Footnotes

The online-only Data Supplement is available with this article at http://atvb.ahajournals.org/lookup/suppl/doi:10.1161/ATVBAHA.116.307985/-/DC1.

Correspondence to Gregory M. Lucas, MD, PhD, 1830 E. Monument St, Room 435A, Baltimore, MD 21287. E-mail

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Highlights

  • HIV infection, cocaine use, and hepatitis C virus infection are overlapping epidemics in many US cities.

  • This study prospectively assessed the independent associations of these nontraditional risk factors with well-validated cross-sectional and longitudinal markers of subclinical cardiovascular disease.

  • We found strong evidence that HIV, cocaine use, and hepatitis C virus infection were independently associated with subclinical cardiovascular disease. There was no evidence of effect modification among these factors.

  • Compared with never use, past and current cocaine use had similar associations with longitudinal cardiovascular disease markers. This suggests that adverse effects from cocaine use were relatively irreversible in this middle-aged cohort.