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Projecting 10-yr, 20-yr and Lifetime Risks of Cardiovascular Disease in Persons Living with HIV in the US - "HIV should be considered a major risk factor for CVD....risk similar to diabetes risk for CVD"
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"we believe that HIV should be considered a major risk factor for CVD.....projected CVD risk among PLWH was similar to those with diabetes"
"Aging PLWH and their health care providers now face new challenges....facilitate discussion between PLWH and clinicians, providing quantitative evidence to guide discussion around CVD risk reduction in PLWH receiving HIV care....critical to test the effectiveness of CVD primary prevention therapies for PLWH"
Given that the projected CVD risk among PLWH was similar to those with diabetes, we believe that HIV should be considered a major risk factor for CVD and that PLWH could benefit from preventive strategies similar to persons with diabetes mellitus. It is critical to test the effectiveness of CVD primary prevention therapies for PLWH.
Our model-based evaluation shows that treatment-adherent PLWH in the US have a greater risk of CVD at younger ages (under 60) compared to both the US general population and the HIV-uninfected, at high risk for HIV population. HIV-infected men remain at higher risk for CVD over their lifetimes, whereas HIV-infected women have lower lifetime CVD risk compared to the US general population. Because SMRs for both HIV-infected women and women at high risk for HIV were substantially higher than those for men, women had lower projected survival than men. This is in contrast to data in the general population where women's life expectancy is generally longer than that of men. The higher SMR in women is explained by the fact that most women with or at risk for HIV have additional risk factors such as drug or alcohol abuse, which puts them at risk for lower life expectancy.
The increased relative CVD risk from HIV is similar to the increased CVD risk due to diabetes (HIV: 1.75; diabetes: 2.1/2.0, M/F) (18, 34). If HIV carries similar cumulative lifetime CVD risk, it is important to investigate the benefit of CVD prevention approaches among PLWH (37, 38). While new evidence suggests that in PLWH only 50% of MIs are of the traditional type (Type 1, from plaque instability), the other 50% are Type 2 MI, or secondary to ischemia due to either increased oxygen demand or decreased supply. This type of MI is more common among persons who inject drugs, who are also less likely to receive the full benefits from ART due to suboptimal adherence (39). A large, ongoing, randomized controlled trial will help illuminate the specific role, if any, of statins as CVD prophylaxis in PLWH given this heterogeneity in MI type (40).
These results can be used in clinical practice to facilitate discussion between PLWH and clinicians, providing quantitative evidence to guide discussion around CVD risk reduction in PLWH receiving HIV care.
CVD cumulative incidence
By age 60, CVD risk was the lowest for males and females in the US general population (12.8% for males and 9.4% for females), higher in the HIV-uninfected, at high risk for HIV cohort (14.6% for males and 9.7% for females), and highest amongst PLWH (20.5% for males and 13.8% for females). For males this ranking continued through their lifetimes, with projected lifetime CVD risk at 54.8% for the US general population, 59.1% for the HIV-uninfected, at high risk for HIV cohort, and 64.8% for PLWH. For females, however, after age 70, the cumulative CVD risk of the US general population began to exceed that of the HIV-uninfected, at high risk for HIV cohort. The projected lifetime CVD risk for US general population females was 46.1%, 36.7% for the HIV-uninfected, at high risk for HIV cohort, and 43.8% for the PLWH cohort (Table 2 and Figure 2 Panels C and D)."
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Projecting 10-yr, 20-yr and Lifetime Risks of Cardiovascular Disease in Persons Living with HIV in the US
CID June 12 2017 - E Losina, PhD , EP Hyle, MD, SM , ED Borre, BA , BP Linas, MD, MPH , PE Sax, MD , MC Weinstein, PhD , C Rusu, BA, BS , AL Ciaranello, MD, MPH , RP Walensky, MD, MPH , KA Freedberg, MD, MSc
Abstract
Background
Cardiovascular disease (CVD) is an increasing cause of morbidity among persons living with HIV (PLWH). We projected cumulative CVD risk in PLWH in care compared to the US general population and persons HIV-uninfected, but at high risk for HIV.
Methods
We used a mathematical model to project cumulative CVD incidence. We simulated a male and female cohort for each of three populations: 1) US general population; 2) HIV-uninfected, at high risk for HIV; and 3) PLWH. We incorporated the higher smoking prevalence and increased CVD risk due to smoking to the HIV-infected and HIV-uninfected, at high risk for HIV populations. We incorporated HIV-attributable CVD risk, independent of smoking.
Results
For men, life expectancy ranged from 70.2-77.5 years and for women from 67.0-81.1 years (PLWH-US general population). Without ART, lifetime CVD risk for HIV-infected males and females was 12.9% and 9.0%.
For males, by age 60, cumulative CVD incidence was estimated at 20.5% in PLWH in care compared to 14.6% in HIV-uninfected high risk persons, and 12.8% in the US general population.
For females, cumulative CVD incidence was projected to be 13.8% in PLWH in care compared to 9.7% for high risk HIV-uninfected persons, and 9.4% in the US general population.
Lifetime CVD risk was 64.8% for HIV-infected males compared to 54.8% in the US general population males, but similar among females.
Conclusions
CVD risks should be a part of treatment evaluation among PLWH. CVD prevention strategies could offer important health benefits for PLWH and should be evaluated.
INTRODUCTION
Due to major advances in the treatment of HIV disease, the life expectancy of treatment-adherent people living with HIV (PLWH) is approaching that of the general population (1). Aging PLWH and their health care providers now face new challenges related to prevention and treatment of common chronic conditions, including cardiovascular disease (CVD) (2).
While numerous studies have focused on the increased risk of CVD in PLWH (3-7) as evidenced by abnormal biomarkers of chronic inflammation and abnormal lipid metabolism, these studies have not estimated lifetime CVD risk at the population level (8). Additionally, many studies compare CVD risk between PLWH and the US general population, but these studies may overestimate CVD risk attributable to HIV by not accounting for the higher prevalence of traditional CVD risk factors, such as smoking, among PLWH (9, 10).
Through simulation modeling, we estimated the lifetime CVD risk in treatment-adherent PLWH, considering competing mortality due to HIV. We compared this lifetime CVD risk to that in the general population, as well as to that in a "high risk" population without HIV infection but with an increased prevalence of behavioral risk factors associated with HIV and CVD and their increased risk of competing mortality.
CVD cumulative incidence
By age 60, CVD risk was the lowest for males and females in the US general population (12.8% for males and 9.4% for females), higher in the HIV-uninfected, at high risk for HIV cohort (14.6% for males and 9.7% for females), and highest amongst PLWH (20.5% for males and 13.8% for females). For males this ranking continued through their lifetimes, with projected lifetime CVD risk at 54.8% for the US general population, 59.1% for the HIV-uninfected, at high risk for HIV cohort, and 64.8% for PLWH. For females, however, after age 70, the cumulative CVD risk of the US general population began to exceed that of the HIV-uninfected, at high risk for HIV cohort. The projected lifetime CVD risk for US general population females was 46.1%, 36.7% for the HIV-uninfected, at high risk for HIV cohort, and 43.8% for the PLWH cohort (Table 2 and Figure 2 Panels C and D).
'Lowest' and 'Highest' CVD risk scenarios for the HIV-infected population
In the 'lowest' CVD risk scenario the cumulative CVD risk by age 60 was 16.7% for males and 8.8% for females; and 54.5% and 16.3% over a lifetime. In the 'highest' CVD risk scenario, the cumulative CVD risk by age 60 was 26.2% for males and 18.7% for females; and 76.3% and 66.8% over a lifetime.
DISCUSSION
Our model-based evaluation shows that treatment-adherent PLWH in the US have a greater risk of CVD at younger ages (under 60) compared to both the US general population and the HIV-uninfected, at high risk for HIV population. HIV-infected men remain at higher risk for CVD over their lifetimes, whereas HIV-infected women have lower lifetime CVD risk compared to the US general population. Because SMRs for both HIV-infected women and women at high risk for HIV were substantially higher than those for men, women had lower projected survival than men. This is in contrast to data in the general population where women's life expectancy is generally longer than that of men. The higher SMR in women is explained by the fact that most women with or at risk for HIV have additional risk factors such as drug or alcohol abuse, which puts them at risk for lower life expectancy.
The increased relative CVD risk from HIV is similar to the increased CVD risk due to diabetes (HIV: 1.75; diabetes: 2.1/2.0, M/F) (18, 34). The projected cumulative lifetime CVD risks for PLWH (ages 50-75) that we report are also similar to the lifetime CVD risk in diabetic patients, despite the competing mortality of HIV disease (diabetes: 67.1/57.3%, M/F, HIV: 64.8/43.8%, M/F) (35). A large body of evidence supports the benefits of CVD prophylaxis for diabetes mellitus, and diabetes is explicitly incorporated into CVD prevention guidelines (36). If HIV carries similar cumulative lifetime CVD risk, it is important to investigate the benefit of CVD prevention approaches among PLWH (37, 38). While new evidence suggests that in PLWH only 50% of MIs are of the traditional type (Type 1, from plaque instability), the other 50% are Type 2 MI, or secondary to ischemia due to either increased oxygen demand or decreased supply. This type of MI is more common among persons who inject drugs, who are also less likely to receive the full benefits from ART due to suboptimal adherence (39). A large, ongoing, randomized controlled trial will help illuminate the specific role, if any, of statins as CVD prophylaxis in PLWH given this heterogeneity in MI type (40).
Our results provide important insights into the potential impact of smoking cessation on CVD lifetime risk in PLWH. One recent study suggests that smoking cessation can dramatically improve life expectancy in PLWH (41).
This study has several limitations. We explicitly model smoking as the major CVD risk factor among persons HIV-uninfected, at high risk for HIV and among PLWH. Other risk factors are modeled implicitly and, as a result, we have limited ability to examine differences in CVD risk due other individual risk factors such as hypertension, impaired glucose tolerance, or dyslipidemia explicitly. Our estimates for lifetime CVD risk in the non-HIV population were consistent with the results of population-based studies (42). Since there is no similar independent data source for PLWH, we made every attempt to inform our estimates using data from population-based studies among PLWH. Additionally, we did not distinguish between mortality from acute and chronic CVD and used aggregated mortality rates from population-based surveys. While we recognize that different subcategories of CVD (e.g., MI, stroke, peripheral vascular disease) may have different short- and long-term mortality (43), using aggregated data allowed us to focus on overall population-based impact. We also did not explicitly investigate the influence of racial and ethnic differences, smoking duration, duration of HIV infection, or means of HIV acquisition, which could all influence CVD risk (44, 45). Lastly, we did not assess the economic impact of CVD care and potential prevention efforts in the current analysis due to the relatively low cost of primary CVD prevention in relation to the cost of ART. A comprehensive analysis of cost related to acute CVD events among PLWH is beyond the scope of this analysis.
These results have important implications for the care of PLWH in the US. While CVD is increasingly recognized as a common cause of death in treated PLWH, additional attention and guidance should be paid to CVD screening and risk factor counseling for PLWH. These results can be used in clinical practice to facilitate discussion between PLWH and clinicians, providing quantitative evidence to guide discussion around CVD risk reduction in PLWH receiving HIV care. Further, to the extent that PLWH in Europe are also living longer, at risk for CVD mortality, and have higher smoking rates than in the US (46), the overall findings of this study may be generalized to these settings.
Given that the projected CVD risk among PLWH was similar to those with diabetes, we believe that HIV should be considered a major risk factor for CVD and that PLWH could benefit from preventive strategies similar to persons with diabetes mellitus. It is critical to test the effectiveness of CVD primary prevention therapies for PLWH.
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