| |
Time to change cardiovascular prevention in people with HIV - A more pragmatic approach is the direct measurement of cIMT to construct cIMT-based monitoring and prevention guidelines for HIV-positive people - comment
|
| |
| |
Download the PDF here
Download the PDF here
Download the PDF here
--------------------
"Our finding that HIV infection is independently associated with subclinical atherosclerosis is consistent with previous studies linking HIV infection with subclinical atherosclerosis and CVD events. However, other studies have not found an association.
Our results are robust because the association of HIV infection with subclinical atherosclerosis is more evident at younger ages, possibly because the low prevalence of traditional risk factors among young adults renders the effect of HIV infection on subclinical atherosclerosis more obvious. Similarly, the weaker or even disappeared associations in older age groups could be because the effect of HIV infection on subclinical atherosclerosis might be overshadowed by the very high prevalence of traditional risk factors and thereby their larger effects on atherosclerosis. Our results might further explain the discrepancy across previous studies showing that significant associations are generally observed in studies in which HIV-positive individuals have either more or similar traditional risk factors or in young age groups.
A notable finding is that 16% of HIV-positive individuals aged between 18 and 29 years had subclinical atherosclerosis. This finding is seldom observed among the HIV-negative individuals from the same age group. Although early onset of subclinical atherosclerosis has been previously observed in young adults with perinatally or early acquired HIV, it is of note that none of our HIV-positive young adults were infected through the mother-to-child route, and few were at intermediate and high risk for CVD as evaluated by FRS. The reasons remain to be investigated. However, these findings suggest the possibility that HIV-positive young adults are at risk of early onset of subclinical atherosclerosis even though they do not acquire HIV perinatally. Because there is insufficient literature examining the progression of subclinical atherosclerosis among HIV-positive young adults using a longitudinal design, it remains unclear whether they are subsequently at risk of accelerated progression to CVD events and what factors can affect the progression.
Although we observe that HIV infection is independently associated with increased subclinical atherosclerosis, in terms of HIV-specific factors, only known duration of HIV infection and not using cART are associated with higher cIMT values. This reinforces the role of HIV infection per se and not ART in the pathogenesis of subclinical atherosclerosis.
Although suppressive cART does not eliminate chronic inflammation caused by HIV infection, it reduces the inflammation and then has a protective effect on atherosclerosis. Reduced progression of cIMT has been also reported in treated HIV infection with viral load suppression. We did not observe an association between nadir CD4 cell count and subclinical atherosclerosis, partly because most of our participants initiated ART shortly after their diagnosis of HIV infection. In another study of mainly HIV-positive women, cIMT was associated with cardiovascular but not ++HIV-related factors. These findings suggest that beyond general HIV-specific and ART-specific factors (eg, CD4 counts and treatment duration), inflammatory or other factors could be important in the link between HIV infection and subclinical atherosclerosis, and for predicting the risk of CVD.
In conclusion, our findings provide evidence that HIV infection is associated with increased carotid artery thickening, independent of traditional risk factors. Such association is stronger at younger ages, which suggests a risk of early onset of subclinical atherosclerosis among HIV-positive young adults. Further research is needed to identify modifiable determinants for prevention and additional markers for CVD prediction among HIV-positive individuals. Our findings are important for HIV care in China, where cardiovascular screening and prevention are not part of routine HIV care. A change in HIV/AIDS treatment guidelines to incorporate routine cardiovascular evaluation into standard care is recommended for HIV-positive individuals even at a young age."
from original study pdf attached
------------------
Comment
Time to change cardiovascular prevention in people with HIV
Lancet HIV Oct 18 2019
Esteban Martinez
Infectious Diseases Unit, Hospital Clínic & University of Barcelona,
Barcelona 08036, Spain
"A more pragmatic approach is the direct measurement of cIMT to construct cIMT-based monitoring and prevention guidelines for HIV-positive people.
In any case, HIV infection itself renders a higher than expected cardiovascular risk. Large studies with hard clinical endpoints of common preventive therapies have not been done on people with HIV.
it seems necessary that people with HIV should have earlier and more aggressive interventions to reduce HIV-related cardiovascular disease risk beyond suppressive ART.
This study provides a common explanation for previous discordant data and confirms that HIV infection alone, even when successfully controlled with suppressive therapy and after adjustment for age, gender, and other known cardiovascular factors, increases the risk of subclinical cardiovascular disease. The influence of HIV infection was better observed at younger ages because it was not overshadowed by the classic risk factors. It is particularly worrisome that 16% of HIV-positive individuals aged between 18 and 29 years had subclinical atherosclerosis.
Framingham risk score and other similar scores used in the general population as predictors of cardiovascular disease, can underestimate subclinical atherosclerosis in people with HIV, limiting their clinical usefulness. Second, people with HIV, even those who are virologically suppressed, have an increased risk of subclinical atherosclerosis; and if they do develop the disease, they might need treatment options other than those offered by the current guidelines, which are the same as the recommendations for the general population."
-------------------------------
Today, people with HIV live longer because of antiretroviral therapy (ART) but experience a higher risk of comorbidities, including atherosclerotic cardiovascular disease.
Increased risk of cardiovascular disease might be due to not only classic risk factors, which are over-represented in the HIV-positive population, but also additional factors not present in the general population. These factors include chronic inflammation associated with HIV infection (even if successfully treated) and the use of some antiretroviral drugs, through mechanisms that are poorly understood.
Because cardiovascular events are rare, assessment of subclinical atherosclerosis measured by carotid artery intima-media thickness (cIMT) has been used as a surrogate marker of cardiovascular disease. cIMT reliably predicts cardiovascular events in the general population.
However, the prognostic value of cIMT in people with HIV is not proven and comparisons of cIMT between HIV-positive and HIV-negative adults have shown discordant data.
In The Lancet HIV, Haijiang Lin and colleagues
evaluated cIMT in HIV-positive adults across different ages and compared it with age-matched and gender-matched HIV-negative adults in Taizhou, China. The authors investigated to what extent the association of HIV infection with subclinical atherosclerosis could be due to a greater prevalence of classic cardiovascular risk factors in people with HIV or if HIV infection is associated with subclinical atherosclerosis, independent of the risk factors. They found that HIV-positive individuals had fewer classic cardiovascular risk factors and lower Framingham risk scores than did HIV-negative individuals. Despite these findings, HIV-positive individuals had a greater prevalence of subclinical atherosclerosis and a higher cIMT than did HIV-negative individuals after adjustment for age, gender, and Framingham risk score. Differences between HIV-positive and HIV-negative individuals were greater at younger ages and decreased gradually with increasing age until no difference was observed. This study provides a common explanation for previous discordant data and confirms that HIV infection alone, even when successfully controlled with suppressive therapy and after adjustment for age, gender, and other known cardiovascular factors, increases the risk of subclinical cardiovascular disease. The influence of HIV infection was better observed at younger ages because it was not overshadowed by the classic risk factors. It is particularly worrisome that 16% of HIV-positive individuals aged between 18 and 29 years had subclinical atherosclerosis.
Lin and colleagues'
study has two important practical implications. First, the Framingham risk score and other similar scores used in the general population as predictors of cardiovascular disease, can underestimate subclinical atherosclerosis in people with HIV, limiting their clinical usefulness. Second, people with HIV, even those who are virologically suppressed, have an increased risk of subclinical atherosclerosis; and if they do develop the disease, they might need treatment options other than those offered by the current guidelines, which are the same as the recommendations for the general population.
The Pooled Cohorts Equation for Atherosclerotic Cardiovascular Disease did better than the Framingham risk score to assess subclinical atherosclerosis in a study of sub-Saharan HIV-positive adults;
however, it underestimated cardiovascular risk in HIV-positive individuals in the USA and Europe.
Tailored risk prediction scores, incorporating cardiovascular risk factors and specific factors related to HIV infection and ART, might result in more accurate risk estimation to guide cardiovascular prevention, but this could be a difficult task requiring large populations of HIV-positive people with a long-follow-up and no guarantee of success. The efforts of the D:A:D group to propose a cardiovascular risk score specifically developed for HIV-positive individuals are laudable,
but it has the same problems of inaccuracy as other general scores and has not become popular. A more pragmatic approach is the direct measurement of cIMT to construct cIMT-based monitoring and prevention guidelines for HIV-positive people.
In any case, HIV infection itself renders a higher than expected cardiovascular risk. Large studies with hard clinical endpoints of common preventive therapies have not been done on people with HIV. Recommending standard preventive measures for people with HIV, which are outlined in major guidelines and recommended for the general population, intuitively makes sense, but it seems necessary that people with HIV should have earlier and more aggressive interventions to reduce HIV-related cardiovascular disease risk beyond suppressive ART. The well-powered REPRIEVE study (NCT02344290), the largest clinical trial ever done in HIV-positive patients, will test whether administration of a statin (pitavastatin) to people with HIV with a low cardiovascular risk will have an effect on major cardiovascular events, subclinical atherosclerosis, inflammatory biomarkers, non-AIDS comorbidities other than cardiovascular disease, and death. If the results of the REPRIEVE study are favourable, they will dramatically affect the prevention of cardiovascular disease in people with HIV and establish a new standard in the clinical care of this population.
I receive grants and personal fees from Gilead Sciences, Merck Sharp & Dohme, and ViiV Healthcare, and personal fees from Janssen, outside the submitted work.
-------------
Age-specific associations between HIV infection and carotid artery intima-media thickness in China: a cross-sectional evaluation of baseline data from the CHART cohort
Summary
Background
Inconclusive results have been reported in studies evaluating the association between HIV infection and subclinical atherosclerosis. Unsolved issues include whether the increased atherosclerosis burden observed in some studies is attributed to greater prevalence of traditional risk factors or HIV infection. Therefore, we evaluated the association of HIV infection with subclinical atherosclerosis as assessed by carotid artery intima-media thickness, while controlling for the effects of traditional risk factors as operationalised by the Framingham risk score (FRS).
Methods
We did a cross-sectional evaluation of data derived from the baseline assessment of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, an ongoing longitudinal study being done in Zhejiang province, China. HIV-positive and HIV-negative individuals aged 18 years and older were recruited between Feb 1, and Dec 10, 2017, and were frequency-matched for age and sex in a 1:2 ratio. Subclinical atherosclerosis was defined as carotid artery intima-media thickness of 780 μm or higher. Logistic regression was used to assess the associations of HIV-positive serostatus and FRS with subclinical atherosclerosis.
Findings
480 of 1425 (36⋅1%, 95% CI 33⋅6-38⋅6) HIV-positive and 784 of 2850 (27⋅5%, 95% CI 25⋅9-29⋅2) HIV-negative individuals had subclinical atherosclerosis (p<0⋅0001), and these patterns remained significant (adjusted odds ratio [adjOR] 1⋅72, 95% CI 1⋅47-2⋅01) in the adjusted model.
After stratifying by age, higher prevalence of subclinical atherosclerosis was observed in HIV-positive than in HIV-negative individuals across the age groups 18-29 years (41 [16⋅0%] of 256 vs 13 [2⋅5%] of 512, p<0⋅0001), 30-44 years (128 [24⋅0%] of 533 vs 153 [14⋅4%] of 1066, p<0⋅0001), and 45-59 years (182 [46⋅6%] of 391 vs 294 [37⋅6%] of 782, p=0⋅0032), but not 60-75 years (163 [66⋅5%] of 245 vs 324 [66⋅1%] of 490, p=0⋅912).
Significant negative interaction between HIV-positive serostatus and age on subclinical atherosclerosis was observed (p<0⋅0001).
ORs adjusted for age, sex, and FRS were 8⋅84 (95% CI 4⋅50-17⋅34) for the age group 18-29 years, 2⋅09 (1⋅59-2⋅74) for 30-44 years, 1⋅54 (1⋅19-1⋅98) for 45-59 years, and 1⋅04 (0⋅75-1⋅44) for 60-75 years.
Among HIV-positive individuals, none of the HIV-specific variables were significantly associated with carotid artery intima-media thickness estimates except for being antiretroviral therapy naive.
Interpretation
HIV infection is associated with subclinical atherosclerosis, independent of classic risk factors. The association is stronger at younger ages, suggesting early onset of subclinical atherosclerosis among young adults. These findings highlight the need to modify HIV/AIDS treatment guidelines to incorporate cardiovascular evaluation in China.
Funding
China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, and Shanghai Municipal Health and Family Planning Commission.
|
|
| |
| |
|
|
|
