|Home | About | Journals | Submit | Contact Us | Français|
HIV patients have increased risk for cardiovascular disease, but the underlying mechanisms remain unknown. The purpose of this study was to determine the prevalence of echocardiographic abnormalities among asymptomatic HIV-infected individuals compared to HIV-uninfected individuals.
We performed echocardiography in 196 HIV-infected adults and 52 controls. Left ventricular ejection fraction (LVEF), left ventricular mass indexed to the body surface area (LVMI), and diastolic function were assessed according to American Society of Echocardiography standards. LVMI was higher in HIV-infected patients (77.2g/m2 in HIV patients vs. 66.5g/m2 in controls, p<0.0001). LVEF was similar in both groups. Eight(4%) of the HIV patients had evidence of LV systolic dysfunction (defined as an EF<50%) versus none of the controls; 97(50%) had mild diastolic dysfunction compared to 29% of the HIV-uninfected subjects (p=0.008). After adjustment for hypertension and race, HIV-infected participants had a mean 8g/m2 larger LVMI compared to controls (p=0.001). Higher LVMI was independently associated with lower nadir CD4 T cell count, suggesting that immunodeficiency may play a role in this process. After adjustment for age and traditional risk factors, HIV patients had a 2.4 greater odds of having diastolic dysfunction as compared to controls (p=0.019).
HIV-infected patients had a higher prevalence of diastolic dysfunction and higher LVMI compared to controls. These differences were not readily explained by differences in traditional risk factors and were independently associated with HIV infection. These results suggest that contemporary asymptomatic HIV patients manifest mild functional and morphological cardiac abnormalities which are independently associated with HIV infection.
Antiretroviral medication has changed the spectrum of HIV infection from a fatal condition to a long term, chronic health condition. According to data from the CDC, by the year 2015, 50% of HIV patients will be over the age of 50 years. Chronic health conditions such as cardiovascular disease will become increasingly important in this growing group of older individuals. In asymptomatic patients without HIV infection, echocardiographic abnormalities such as diastolic dysfunction as assessed by decreased mitral inflow E/A ratio and increased left ventricular mass have been associated with all-cause mortality.(1) In children with HIV, mild depression of LV systolic function and elevated LV mass were associated with increased all-cause mortality.(2) Prior studies of cardiac abnormalities in HIV patients before the antiretroviral era demonstrated a high prevalence of dilated cardiomyopathy and pericardial effusion.(3,4) There have been relatively few studies addressing cardiac abnormalities detectable by echocardiography among adults in the modern era. A study of HIV-infected African American men who were cocaine users demonstrated that individuals taking protease inhibitors had higher interventricular septal thickness, higher left ventricular posterior wall thickness and decreased E/A ratio.(5) Recently, in a study of 30 HIV-infected men and uninfected controls, HIV patients were found to have a higher prevalence of diastolic dysfunction, lower calculated ejection fraction, and higher pulmonary artery pressure compared to uninfected controls.(6) As only treated patients were included, the role of antiretroviral therapy including protease inhibitors could not be assessed independently of HIV infection.
The purpose of our study was to determine the prevalence of echocardiographic abnormalities among asymptomatic HIV-infected individuals compared to uninfected controls and to ascertain the independent contributions of HIV infection, detectable viremia, and antiretroviral therapy to those findings.
We recruited individuals with HIV infection from a large clinic-based cohort at San Francisco General Hospital (Study of the Consequences of the Protease Inhibitor Era). This cohort includes 1) untreated patients, defined as no antiretroviral therapy in the preceding 6 months, 2) treated patients with detectable viremia, defined as >24 weeks antiretroviral therapy with the most recent two HIV RNA levels >75 copies/mL, and 3) treated patients who achieved full viral suppression defined as >24 weeks antiretroviral therapy with two most recent HIV RNA levels <75 copies/mL. All participants were documented to be HIV-infected either by medical records, letter of diagnosis, or HIV- antibody testing. Participants were consecutive volunteers from the SCOPE study; the only inclusion criterion was HIV infection, and there were no other inclusion or exclusion criteria related to cardiovascular disease or traditional cardiovascular risk factors. For the uninfected control group, participants were persons who responded to advertisements for enrollment in clinical research studies directed towards persons believed to be HIV-uninfected. We targeted our enrollment of controls to individuals of similar age, gender, and smoking status to our HIV-infected population. All persons in this group were tested and documented to be HIV-antibody-negative prior to enrollment in the study. All participants provided written informed consent; the study was approved by the UCSF Committee on Human Research.
We conducted a detailed interview with all study participants which included information on traditional cardiovascular risk factors, medication use, sociodemographic features, and activity tolerance using the New York Heart Association classification. Hypertension, diabetes mellitus, and hyperlipidemia were defined by patient self report and verified by chart review or were defined by being currently treated with medications for blood pressure, diabetes, or hyperlipidemia. Confidential self-administered questionnaires were used to ascertain the use of illicit drugs, including heroin, cocaine and amphetamine/methamphetamine, and a history of their intravenous administration. The HIV-infected participants had comprehensive assessment of their HIV disease related aspects including HIV medication usage, opportunistic infections, and nadir CD4 count.
A single sonographer who was blinded to each participant’s HIV status and clinical characteristics performed all of the echocardiographic studies. We determined the presence of diastolic dysfunction according to guidelines from the American Society of Echocardiography (ASE).(7–9) Using a Vivid 7 Imaging System (GE, Milwaukee, WI), diastolic dysfunction was assessed using spectral Doppler mitral and pulmonary venous inflow velocity patterns and Doppler tissue imaging of the lateral mitral annulus. Three consecutive cardiac cycles were assessed and averaged for Doppler measurements. Stage 1 diastolic dysfunction was defined as impaired relaxation; Stage 2 diastolic dysfunction was defined as a pseudonormal filling pattern. Stage III diastolic dysfunction was defined as a restrictive filling pattern and evidence of reversibility with Valsalva maneuver, and finally, Stage IV was defined as a restrictive filling pattern without reversibility with Valsalva.(10,11) Left ventricular end-diastolic and end-systolic volumes, ejection fraction, and left atrial volumes were assessed using the modified Simpson’s rule, and indexed to body surface area. Left ventricular mass was measured from midventricular short axis slice and long axis measured from the apical four chamber view; LV mass was indexed to body surface area. Reference limits from the ASE were used to determine left ventricular hypertrophy (LVH) for both men and women.(12) Tricuspid regurgitation was assessed in 3 different views, and 3 sequential complexes were recorded. Continuous-wave Doppler measurement of the peak regurgitant jet velocity from any view was used to estimate the systolic pressure gradient between the right ventricle and the right atrium using the modified Bernoulli equation.(13) Pulmonary artery systolic pressure (PASP) was quantified by adding the calculated pressure gradient to the mean right atrial pressure, which was estimated from the diameter of the inferior vena cava, degree of inspiratory collapse, and hepatic vein Doppler profile using ranges from 0–5mm Hg, 5–10mm Hg, 10–15mm Hg, 15–20mm Hg, and > 20.mm Hg.(12) The severity of mitral regurgitation was assessed as Grade 1 through 4 using standard echocardiographic criteria.(14,15) All calculations and interpretations were performed off-line by two cardiologists (JEH, HHF) who were blinded to participants’ HIV infection and clinical status.
The Triage B-Type Natriuretic Peptide Test (Biosite Inc., San Diego, CA) was used to measure B-type natriuretic peptide (BNP).(16) Hepatitis C virus (HCV) serostatus was determined by the HCV EIA version 2.0 (Abbott Laboratories, Abbott Park, IL). The nadir CD4+ T cell count was the lowest laboratory-confirmed value prior to the echocardiography date. High sensitivity C-reactive protein was measured using the Dade Behring assay.
For continuous variables, unadjusted comparisons between groups were made using Kruskal-Wallis tests and then pairwise Wilcoxon ranksum tests; for categorical variables, chi-square and Fisher’s exact tests were used. The Spearman’s rank correlation coefficients were used to assess correlations between continuous variables. Linear and logistic regression were used to assess adjusted differences between groups. Continuous variables were transformed, and standard errors were calculated using heteroskedasticity-consistent covariance matrix estimators to satisfy model assumptions when needed.(17) Age, gender, race, history of injection drug use, amphetamine, or cocaine use (ever vs. never used), current cigarette use, and the diagnoses of hypertension, diabetes mellitus, hyperlipidemia, and hepatitis C virus infection were all considered as potential confounders. Potential confounders that were associated with the outcome of interest (in our study, diastolic dysfunction or higher left ventricular mass index) at the P<0.10 level in unadjusted analyses were assessed in multivariate models but then removed in a stepwise manner if their inclusion changed the beta coefficient of the primary predictor by less than 10%. Sensitivity analyses were also performed restricting the analysis to those patients who reported never using amphetamines or cocaine or who did not have a history of hypertension.
Sample size estimates for differences in means and proportions between groups were estimated with the sampsi command in Stata 10.0. To determine the number of patients for our study, we based our sample size calculation on a prior study of 30 HIV infected patients and 26 uninfected controls which showed a higher prevalence of LV diastolic dysfunction in 64% of patients vs. 12% of controls.(6) Since we were recruiting a larger number of HIV-infected participants receiving antiretroviral therapy and an older control population enriched for smokers, we assumed that the difference in prevalence of diastolic dysfunction between HIV-infected participants and uninfected controls might be as small as 40% vs. 20%. Assuming a Type I error rate of 5%, we would have 80% power to detect a difference this small between groups by enrolling 196 HIV-infected individuals and 52 uninfected controls. We oversampled HIV-infected participants so that we could examine the relationship between antiretroviral therapy treatment status and presence of detectable viremia on left ventricular mass index. While underpowered to detect differences in the presence of diastolic dysfunction by treatment status or presence of detectable viremia, with 168 treated and 28 untreated HIV-infected participants and 128 with undetectable vs. 68 with detectable viremia, a Type I error rate of 5%, a standard deviation in left ventricular mass index (LVMI) of 17g/m2, we had 80% power to detect a difference between treated and untreated participants as small as 10g/m2 and a difference between those with and without detectable viremia as small as 7g/m2.
As shown in Table 1, 196 HIV-infected and 52 uninfected controls were studied. Over 80% of participants in both groups were men. The median age was 47 years in the HIV-infected group and 45 years in the uninfected controls. Most of the HIV patients and controls were Caucasian; there was a higher percentage of African-American individuals in the HIV-infected group (25 vs. 8%). Thirty-six percent of the HIV patients were current smokers compared to 26% of the uninfected controls (p=0.13). The rates of IVDU and methamphetamine use were higher in the HIV-infected patients (see Table 1). More of the HIV patients had a history of hypertension compared to uninfected controls (26% vs. 6%) and similarly, more of the HIV patients were on antihypertensive medications compared to uninfected controls (21% vs. 4%). However, the average systolic blood pressure was similar in the HIV patients and uninfected controls (122.4 mm Hg vs. 122.6 mmHg, respectively, p=0.92) as was the average diastolic blood pressure (77.0 mm Hg in the HIV patients vs. 77.8 mm Hg in the uninfected controls, p=0.63). Rates of diabetes mellitus, prior coronary artery disease, and hyperlipidemia were low and similar between the groups. Only 7 (2.8%) of all participants experienced class II or higher New York Heart Association activity tolerance, and all were class II.
Among the HIV-infected participants, the median duration of HIV diagnosis was 15 years, and 82% were currently using antiretroviral medication, while only 8% were treatment naïve. Among the subset being currently treated, the median duration of protease inhibitor use was 5.3 years, the median duration of nucleoside reverse transcriptase inhibitors was 7.9 years, and 63% percent had an undetectable viral load. Among all HIV-infected participants, the median CD4+ T cell count was 420 cells/mm3 and the median CD4+ T cell nadir was 120 cells/mm3.
Baseline echocardiographic parameters are summarized by HIV status in Table 2. The median ejection fraction was similar in HIV-infected individuals (median 63%, interquartile range 59 to 67) and uninfected controls (median 62%, IQR 59 to 67) (p=0.63). Eight (4%) of the HIV patients had an ejection fraction less than 50% (range 33–49%) while none of the controls had an ejection fraction below 50% (p=0.21). Left atrial volume indices were higher in HIV-infected participants (median 26, IQR 21 to 30) compared with uninfected controls (median 20, IQR 16 to 25, p < 0.001). Seven HIV-infected participants (4%) and 1 uninfected control (2%) had Grade 2 mitral regurgitation (p=0.55); no subject had Grade 3 mitral regurgitation. As we have previously reported,(18) the median pulmonary artery systolic pressure among the HIV-infected participants was higher (median 27.5 mm Hg, IQR 22 to 32.5) than the uninfected controls (median 22 mm Hg, IQR 18 to 25) (p < 0.001, Wilcoxon rank sum). The median right atrial pressure was 5 mm Hg in both HIV patients and controls. Using ASE criteria,(12) seven (4%) of the HIV patients had evidence of LVH as compared to 1 uninfected control (2%) (p=0.55).
Ninety-seven (49%) HIV-infected participants had evidence of diastolic dysfunction compared to only 15 (29%) uninfected controls (p=0.008). In 6 HIV patients, diastolic dysfunction could not be assessed (1 due to atrial fibrillation and 5 due to fusion of the E and A waves). In general, HIV-infected participants had lower E/A ratios and longer deceleration times on spectral Doppler assessment of mitral valve inflow when compared with uninfected controls (p=0.03 for both parameters). Tissue Doppler imaging revealed significantly lower mitral annular E’ velocities in HIV infected compared with uninfected controls (p < 0.001). Almost all of the diastolic dysfunction was Stage 1; only 2 HIV-infected individuals had Stage II diastolic dysfunction. In unadjusted analyses including all study participants, diastolic dysfunction was associated with older age (p<0.001) and hypertension (p=0.002). There was no evidence for an association between diastolic dysfunction and gender, diabetes mellitus, prior CAD, current cigarette smoking, hepatitis C virus infection, injection drug use (current or ever), amphetamine or cocaine use (current or ever), or race (p>0.10). After adjustment for age and hypertension, individuals with HIV infection had a 2.4-fold greater odds of having diastolic dysfunction compared to uninfected individuals (p=0.019, Table 3). After restricting the analysis to patients who did not have hypertension, HIV-infected individuals still had a 2.4 increased risk of diastolic dysfunction (p=0.024) even after adjusting for age. Similarly, when restricting the analysis to participants reporting never to have used amphetamines or cocaine, HIV infection was independently associated with a higher risk of diastolic dysfunction in both unadjusted analysis (p=0.01) and analyses adjusted for age and hypertension (p=0.048).
Compared to those without diastolic dysfunction, HIV-infected participants with diastolic dysfunction had lower current CD4 T cell counts (median 380 vs. 460 cells/mm3, p=0.054) and a longer duration of NRTI use (8.4 vs. 6.9 years, p=0.005). However, after adjustment for age and hypertension, these associations were no longer significant (p>0.17 for each). There was no evidence for a relationship between diastolic dysfunction and current plasma HIV RNA level or duration of either protease inhibitor or NNRTI use (p>0.14 for all).
We also compared the antiretroviral-treated subset (n=168) with the HIV uninfected subjects, and found the same inferences. Of the 168 treated subjects, 84 had evidence of diastolic dysfunction, which was significantly higher than the HIV uninfected group (p=0.007). These differences remained significant after controlling for age and hypertension (p=0.018). Among the treated patients, a longer duration of NRTI use was associated with diastolic dysfunction (p=0.002) but again this was not significant after adjusting for age and hypertension (p=0.10).
Overall, the LV mass index was significantly higher among individuals with HIV as compared to uninfected controls (77.2 g/m2 vs. 66.5 g/m2, p=0.0001). Among all study participants, a higher LV mass index was associated with older age (p=0.03), male gender (p<0.001), and hypertension (p=0.007). Self-identified Latino race (compared to all other racial groups, p=0.017) was associated lower LV mass index. There was no evidence for a relationship between left ventricular mass index and hyperlipidemia, current cigarette smoking, injection drug use (current or prior use), or prior CAD in unadjusted analyses (all p>0.20). After adjustment for hypertension and Latino race, HIV-infected individuals had a mean 8 g/m2 higher LV mass index than uninfected controls, p=0.001 (Table 4). Even when restricting the analysis to participants reporting never to have used amphetamines or cocaine, HIV infection continued to be independently associated with higher LV mass index in both unadjusted (p=0.009) and adjusted analyses (p=0.008). LV mass index values exceeded the gender-specific normal range in 4% of HIV-infected subjects and 2% of uninfected controls (p = 0.55)
Among HIV-infected individuals, lower self-reported nadir CD4 cell count was borderline associated with a higher LV mass index (Spearman’s rho: −0.14, p=0.052, Figure 1). Even after adjustment for gender and hypertension, each 100 cell/mm3 decrease in self-reported nadir CD4+ T cell count was associated with a mean 1.3g greater LV mass (p=0.013). There was no evidence for a relationship between LV mass index and either current CD4+ T cell count or plasma HIV RNA level (p>0.13 for both). While a longer duration of NRTI use was associated with higher LV mass index in unadjusted analyses (Spearman’s rho: 0.15, p=0.037), the relationship was not significant after adjustment for nadir CD4+ T cell count (p>0.14). Neither duration of NNRTI or protease inhibitor use was associated with LV mass index.
We also compared the antiretroviral-treated subset (n=168) with the uninfected controls, and found similar results. The LV mass was higher in the treated subjects than the uninfected controls (p<0.001)). These differences remained significant after controlling for hypertension and Latino race (p=0.001). Among the treated patients, there was no evidence for a relationship between current CD4 count, nadir CD4 count, viral load, or duration of antiretroviral therapy and LV mass index (p>0.10 for all). While the HIV-infected group was significantly enriched for African American individuals relative to the uninfected controls, among all participants, there was no evidence for a relationship between African American race and diastolic dysfunction (p=0.74) or LV mass index (p=0.23). Thus, the enrichment of African Americans in the HIV-infected group is unlikely to confound the observed differences in diastolic dysfunction and LV mass index between the groups.
Plasma BNP levels were available on 227 participants; the median level was 5 pg/ml (IQR 2 to 12). The BNP levels were significantly higher among the HIV-infected patients (6pg/ml vs. 3pg/ml, p=0.002) and higher BNP was associated with a higher LV mass index (p=0.005). There was no association between BNP and diastolic dysfunction (p=0.84). Across all subjects, a higher BNP was associated with a higher PASP (Spearman’s rho = 0.22, p < 0.001).
Serum hsCRP levels were available on all patients; there was a trend toward higher hsCRP levels among the HIV-infected individuals compared to uninfected controls (2.5mg/dL vs. 2.2mg/dL, p=0.11). However, there was no association between higher hsCRP levels and diastolic dysfunction (p=0.24) nor was there any association between hsCRP levels and higher LV mass index (p=0.53).
According to data form the Joint United Nations Programme on HIV/AIDS, there are over 33 million people living with HIV/AIDS world-wide(19) and over 1.1 million in the U.S.(20) Recently, the number of individuals aged 50 years and older living with HIV/AIDS has increased dramatically: in 2005, persons aged 50 and over accounted for 15% of new HIV/AIDS diagnoses and 29% of persons living with AIDS. (21) As this population continues to age, chronic health conditions such as cardiovascular disease will likely increase in importance. Higher rates of cardiovascular disease have already been reported in individuals with HIV infection(22) along with higher rates of subclinical atherosclerosis.(23,24) The widespread availability of combination antiretroviral therapy has resulted in dramatic reductions in the risk of AIDS-defining complications among HIV-infected patients. The impact of HIV infection (and its treatment) on cardiac function has not been well described, even though this is a common source of morbidity and mortality in aging HIV-uninfected patients. Here, we show that significant structural abnormalities such as decreased ejection fraction, valvular heart disease, and LVH are not more common in a well characterized contemporary group of HIV patients (most of whom had been on long term antiretroviral therapy) compared to uninfected controls. At the same time, we do demonstrate that HIV disease is independently associated with both diastolic dysfunction, increased left atrial volumes, and increased LV mass index. All of these outcomes have been associated with higher mortality among uninfected patients.(1,25) These observations support the growing concern that HIV infection may be linked with these diseases that have traditionally been associated with aging.(26)
In our study, LV mass index was higher in HIV-infected individuals than the uninfected controls; this was true even after limiting our analysis to those without prior illicit drug use and to those without hypertension. The LV mass index, while elevated, did not exceed the gender-specific upper limit of normal in the majority of individuals and therefore did not imply clinical levels of left ventricular hypertrophy. Among our HIV-infected patients, a lower nadir CD4 count was associated with higher LV mass index. This finding was independent of risk factors that are traditionally associated with elevated LV mass including age, race, gender, diabetes mellitus, and hypertension. An association between LV mass index in HIV-infected women has been previously described, although this finding was no longer significant after adjusting for age.(27) It is possible that HIV effect on LV mass may be secondary to subclinical atherosclerosis. We did not detect an association between prior coronary artery disease and LV mass index, although there were only 5% of HIV patients with a history of CAD in our study. Our group has previously demonstrated an association between nadir CD4 count and subclinical atherosclerosis as assessed by carotid artery intima-media thickness (IMT) in individuals with HIV infection(28) and other groups have found an association between CD4 and cardiovascular events.(29) Of note, the nadir CD4+ T-cell count has been strongly associated with the level of immune activation; in turn, even among antiretroviral treated patients, the levels of immune activation remain elevated.(30) The higher levels of inflammation present in HIV patients may in theory contribute to increased LV mass, as has been suggested in studies of HIV-uninfected adults including individuals with systemic lupus erythematosus(31) and rheumatoid arthritis.(32)
The pathogenesis of HIV-associated diastolic dysfunction is likely multifactorial. First, although it remains controversial, several studies suggest that hypertension is associated with antiretroviral use, including prolonged duration of antiretroviral therapy(33) and treatment with protease inhibitors.(34,35) Hypertension was common in our HIV-infected study participants; however, this factor alone was unlikely to account for our findings as we still found an independent association between HIV infection and diastolic dysfunction both after adjustment for hypertension as well as after restricting the analysis to individuals without hypertension. Second, the increase in LVMI that we detected in our study may underlie the finding of mild diastolic dysfunction among HIV patients. Third, it is possible that HIV or other associated viral infection may directly affect the myocardium. HIV-1 has been detected in endomyocardial biopsy specimens in HIV patients with LV dysfunction(36) while other autopsy studies have detected sequences of HIV-1 in myocytes of HIV patients at autopsy.(37) Fourth, our group and others have shown that individuals with HIV infection have high rates of inflammation(23,28) which may predispose HIV patients to diastolic dysfunction. In the uninfected population, higher levels of inflammatory markers such as hsCRP have been shown to be associated with diastolic dysfunction.(38,39) Reversible and isolated diastolic dysfunction has been shown to occur in individuals with septic shock, a condition characterized by high levels of inflammation,(40) as well as in the setting of chronic inflammatory states such as rheumatoid arthritis.(41) Fifth, in unadjusted analysis lower CD4 count and longer duration of NRTI use were associated with diastolic dysfunction, suggesting that advanced immunodeficiency and/or side effects from medication may mediate the development of this abnormality. NRTI use has previously been associated with cardiomyopathy and mitochondrial damage.(42) Finally, subclinical atherosclerosis as assessed by carotid artery intima-media thickness is common in HIV-infected individuals,(24,28) and therefore another possible mechanism underlying diastolic dysfunction may be underlying ischemic heart disease as well as increased arterial stiffness which has been reported in HIV patients.(43,44) In our study, diastolic dysfunction was not associated with a prior history of coronary artery disease, but only 5% of HIV-infected individuals studied had this diagnosis.
The results of our study demonstrate that the echocardiographic findings associated with HIV infection during the early years of the epidemic have shifted. Left ventricular systolic dysfunction, right ventricular enlargement, and pericardial effusions were common findings before the widespread usage of antiretroviral medications.(3,4) Prior studies demonstrated that pericardial effusions were associated with reduced survival,(45) and persistently low ejection fractions were associated with a high one year mortality rate.(46) Our study suggests that LV and RV systolic dysfunction and pericardial effusions are now rare, while mild diastolic dysfunction is common. The low rate of LV systolic dysfunction that we detected in our study may bode well for the aging HIV population.
Our study was cross-sectional in nature and hence has several limitations commonly associated with this study design. Specifically, since our primary outcomes likely reflect a life-time of exposure to various risk factors, and since many of these factors are difficult to quantify retrospectively, a longitudinal study in which all such factors are measured is now needed. Still, we believe that our data are highly relevant, as they expand upon those of earlier studies(5,6) by using advanced techniques to assess diastolic dysfunction, by being carefully restricted and adjusted for potential confounders, and by including an uninfected control group.
The long term clinical implications of our findings remain unclear. Among large population-based studies of asymptomatic middle aged adults, diastolic dysfunction was strongly associated with both all-cause and cardiac mortality.(47,48) Although unstudied at this time, it is likely that diastolic dysfunction will be predictive of mortality in the HIV population as well. Our findings suggest that caregivers should maintain a high clinical suspicion for cardiovascular disease, aggressively treat all traditional cardiovascular risk factors, and consider the possibility of diastolic dysfunction in HIV-infected individuals. However, in the absence of symptoms, we believe it is premature to recommend routine screening echocardiograms for HIV-infected adults.
It is also unclear as to whether the HIV-infected patients require any unique therapeutic interventions to manage or prevent cardiac dysfunction. Reduction of HIV-related inflammation using antiretroviral therapy would appear to be a reasonable approach, although the benefit of treatment on cardiac function remains unproven. Several studies including the SMART study and ACTG 5142 suggest that using antiretroviral therapy prevents cardiovascular disease-associated outcomes (e.g., myocardial infarction), at least in the short term.(49,50) These studies were not able to specifically address the impact of antiretroviral treatment on cardiac function, but given the strong association between atherosclerotic disease and cardiac function, it is reasonable to assume that effective antiretroviral treatment will be beneficial. Longer term studies along with further investigations into the pathogenesis of HIV-associated cardiovascular disease will be essential in guiding standards of clinical care in the future.
Funding Sources: The work was supported by grants from the Doris Duke Charitable Foundation (Clinical Scientist Development Award to PYH), the American Heart Association (Beginning Grant-in-Aid to PYH), the NIH (R01 HL095126, R01 AI052745, R01 CA119903, P30 AI27763 and MO1 RR000083) and the University of California AIDS Research Program California AIDS Research Center (CC99-SF-001).
Presented in part at the 80th Scientific Sessions of the American Heart Association, Orlando, November 3–7, 2007.