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. Author manuscript; available in PMC: 2019 Sep 11.
Published in final edited form as: Circulation. 2018 Sep 11;138(11):1100–1112. doi: 10.1161/CIRCULATIONAHA.117.033369

Global Burden of Atherosclerotic Cardiovascular Disease in People Living with the Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis

Anoop SV Shah 1,2, Dominik Stelzle 3,4, Kuan Ken Lee 1, Eduard J Beck 3, Shirjel Alam 1, Sarah Clifford 1, Chris T Longenecker 5, Fiona Strachan 1, Shashwatee Bagchi 6, William Whiteley 7, Sanjay Rajagopalan 5, Shyamasundaran Kottilil 6, Harish Nair 2, David E Newby 1, David A McAllister 8, Nicholas L Mills 1
PMCID: PMC6221183  EMSID: EMS78655  PMID: 29967196

Abstract

Background

With advances in anti-retroviral therapy, most deaths in people with human immune-deficiency virus (HIV) are now due to non-communicable illnesses especially cardiovascular disease. We determine the association between HIV and cardiovascular disease, and estimate the national, regional and global burden of cardiovascular disease attributable to HIV.

Methods

We conducted a systematic review across five databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection. A random-effects meta-analysis across eighty studies was used to derive the pooled rate and risk of cardiovascular disease in people living with HIV. We then estimated the temporal changes in the population attributable fraction and disability-adjusted life years (DALYs) from HIV associated cardiovascular disease from 1990 to 2015 at a regional and global level. National cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193 United Nations member states. The main outcome measure was the pooled estimate of the rate and risk of cardiovascular disease in people living with HIV and the national, regional and global estimates of DALYs from cardiovascular disease associated with HIV.

Results

In 793,635 people living with HIV and a total follow-up of 3.5 million person-years, the crude rate of cardiovascular disease was 61.8 (95% confidence interval [CI] 45.8-83.4) per 10,000 person-years. Compared to individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95%CI 1.68-2.77). Over the last 26 years, the global population attributable fraction from cardiovascular disease due to HIV increased from 0.36% (95%CI 0.21-0.56%) to 0.92% (95%CI 0.55-1.41%) and DALYs increased from 0.74 (95%CI 0.44-1.16) to 2.57 (95%CI 1.53-3.92) million. There was marked regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95%CI 0.43-1.70) and the Asia-Pacific (0.39 million, 95%CI 0.23-0.62) regions. The highest population attributable fraction and burden was observed in Swaziland, Botswana and Lesotho.

Conclusions

People living with HIV are twice as likely to develop cardiovascular disease. The global burden of HIV associated cardiovascular disease has tripled over the last two decades and is now responsible for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa and the Asia-Pacific regions.

PROSPERO Registration

URL: https://www.crd.york.ac.uk/prospero. Unique identifier: CRD42016048257.

Keywords: stroke, myocardial infarction, cardiovascular disease, HIV, global burden

Currently more than 35 million people are infected with the human immunodeficiency virus (HIV) with two-thirds being resident in sub-Saharan Africa.1 Although the global incidence for HIV has stabilised, the provision and widespread distribution of combined anti-retroviral therapy has 2 dramatically improved survival with the prevalence of HIV steadily increasing over the last two decades.3 This improvement in survival has been primarily attributed to a reduction in opportunistic infections especially in the low- and middle-income nations.1, 4 Indeed, most deaths now arise from non-communicable illnesses especially cardiovascular disease.5–7

Cardiovascular disease is the leading cause of morbidity and mortality worldwide.8, 9 The last two decades has seen a substantial increase in the morbidity due to cardiovascular disease with a significant proportion of the burden borne by low- and middle-income nations.10, 11 The highest prevalence rates of HIV have been observed in sub-Saharan Africa. This region has also seen a steady increase in the burden of cardiovascular disease over the last two decades.2, 12 Recent studies have shown a link between the development of cardiovascular disease and HIV infection with multiple potential mechanisms including direct vascular inflammation,13, 14 dyslipidaemia15 and insulin resistance.16, 17

The aim of this systematic analysis was to review and to meta-analyse the rate of cardiovascular disease in people living with HIV, to determine the association between HIV infection and risk of cardiovascular disease, and to estimate the national, regional and global burden of HIV associated cardiovascular disease.

Methods

Data and the corresponding R analysis code will be available at https://github.com/anoopsshah/hiv_cvd.

Databases, sources and searches

We searched MEDLINE, EMBASE, Global Health, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science using the following keywords: ‘myocardial infarction’, ‘stroke’, ‘cerebrovascular disease’, ‘cardiovascular disease’ and ‘HIV’ (Supplementary Text 1). Bibliographic reference lists of studies selected for inclusion in our meta-analysis and relevant review articles were manually searched (Figure 1). We limited our search to studies published between 1948 and 30th August 2016.

Figure 1. Flow chart.

Figure 1

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Flow chart of studies meeting the inclusion criteria of the systematic review and meta analysis.

Selection of articles, extraction of data and data synthesis

All longitudinal studies including case-control, cohort and randomised control trials were included. There were no language restrictions and only peer-reviewed original articles were included. Many studies provided data on the same cohort at extended follow-up time points. In such cases, we selected the published study with the longest follow-up period. Data were extracted independently and any discrepancies adjudicated by four investigators (AS, DS, KL and SA). We contacted authors for additional data or clarification where required. The study methodology, results and presentation were conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Supplementary Table 1).18

Crude rate

The pooled incident crude rates of cardiovascular disease, studies were only included if they provided the number of cardiovascular events (fatal or non-fatal myocardial infarction or stroke) and the follow-up period. Crude incidence rates were pooled per 10,000 person-years and presented for all incident cardiovascular events and deaths. The analysis was sub-stratified by aetiology classified as either myocardial infarction or cerebrovascular disease, where applicable.

Risk ratio

For estimating the pooled risk ratios of cardiovascular disease, cases were defined as any hospitalisation with, or mortality from, cardiovascular events (fatal or non-fatal myocardial infarction or stroke) in individuals with and without HIV. Studies were also included if the outcome was defined as a cardiovascular event and included but was not exclusive to myocardial infarction and/or stroke. Risk ratio (RR) estimates for disease incidence and case fatality for cardiovascular events in HIV-infected populations compared with HIV-uninfected populations were pooled and presented with 95% confidence intervals.

Pooled risk ratio estimates were assessed for publication bias by visually assessing funnel plots and assessed for asymmetry using Egger’s regression test.19 The 'trim and fill' method was used to adjust for selection bias due to potential unpublished studies or bias due to small-study effects.20 Sensitivity analysis was performed by removing studies where adjustment for important confounders was omitted (Supplementary Table 2). Across both the pooled rate and risk ratios, subgroup analysis was only performed where three or more estimates were available. Studies providing estimates for the risk ratio were further stratified by type of event and publication year.

Regional and global estimates for HIV prevalence and cardiovascular disability adjusted life years

Global and regional estimates of cardiovascular disease attributable to HIV were derived annually from 1990 to 2015.

Cardiovascular disability adjusted life years

National disability-adjusted life year (DALY) estimates for cardiovascular disease (consisting of the sum of disability-adjusted life years due to ischaemic heart disease and stroke) were available from the Institute of Health Metrics and Evaluation. Countries were grouped into UNAIDS regions (Supplementary Table 3). The disability-adjusted life years for cardiovascular disease in each country were summed to derive the regional cardiovascular burden. These data were available at 5-year intervals, from 1990 to 2015, with intervening years being obtained via linear interpolation.

Regional prevalence of HIV

Prevalence estimates for HIV were available from 1990 to 2015, for the adult population from 15 years to 49 years of age, from UNAIDS at a global and regional level.

Population attributable fraction and HIV attributable cardiovascular DALYs

At the global and regional level, we applied the HIV prevalence estimates for the 15-49 year age group across the entire adult population. As such the calculated the population attributable fraction was applied to the entire adult population when calculating the cardiovascular DALYs attributable to HIV at a global and regional level.

National estimates for HIV prevalence and cardiovascular disability adjusted life years

National estimates of HIV prevalence and cardiovascular burden were available from 160 and 179 countries respectively of the 193 United Nations member states, and both were available from 154 countries. Ntaional HIV prevalence estimates were available for the >15 years age group for 2016 and national disability-adjusted life year estimates for cardiovascular disease were available for 2015.

We also calculated estimates of burden in the nations with a high HIV prevalence by combining data for the UNAIDS defined 21 Global Plan priority countries (Supplementary Table 3).21, 22 National level data for cardiovascular DALYs for 2015 and HIV prevalence for 2016 were available for 20 of the 21 Global Plan priority countries (Supplementary Table 3).

Statistical analysis

Using the pooled risk ratio for cardiovascular disease in people living with HIV and the prevalence of HIV, we estimated the population attributable risk fraction at national, regional and global levels. At regional and global levels, we further estimated the yearly changes in attributable risk to take into account temporal changes in the population prevalence of HIV. The population attributable fraction for HIV for cardiovascular disease was calculated as described previously:23, 24

PopulationAttributableFraction=Prevalence∗(RR−1)1+Prevalence∗(RR−1)

We anticipated heterogeneity between studies when estimating both the crude incidence rates and the risk ratio due to different study designs, methods of analysis and varying adjustment, and geographical and population differences. We therefore used a random-effects model with the maximum likelihood estimator to account for both within and between study heterogeneity.25 Heterogeneity, when estimating the pooled estimate of the risk ratio, was examined using the standard I2 test. Publication or small-study bias was assessed using the regression test and the trim and fill method used for correcting funnel plot asymmetry. Risk of bias was assessed at a study level according to the level of adjustment undertaken (Supplementary Table 2). Studies at low risk of bias were defined if adjustment of age, sex and at least one other covariate was undertaken. Moderate risk was defined as adjustment of at least age or sex and studies were classified as high risk if no adjustment was undertaken. Full statistical methods are explained in the supplementary material (Supplementary Text 2, Supplementary Figure 1a and 1b). All analyses were performed in R Version 3.2.3 with the estimates derived using the metafor package. Statistical significance was taken as a two-sided P<0.05.

Results

A total of 80 studies were identified to estimate the rate and risk ratio of cardiovascular disease in people living with HIV. One hundred and twenty-two estimates from 73 studies were used to calculate the pooled crude incident rates of fatal and non-fatal cardiovascular disease in people living with HIV (Supplementary Table 4, Figure 1). This comprised of 793,635 people with HIV and a total follow-up of 3.5 million person-years. The crude incidence rate for cardiovascular disease per 10,000 person-years was 61·8 (95% confidence interval [CI] 45·8 to 83·4). When stratified by incident myocardial infarction and stroke, the rate was 25·9 (95% CI 20·3 to 33·0) and 17·9 (95% CI 13·2 to 24·3) respectively (Supplementary Figure 2a-c). The cardiovascular mortality rate was 14·1 per 10,000 person years (95% CI 10·3 to 19·4) (Supplementary Figure 2d-f). Of the 122 estimates, only 12 (9.8%) estimates (across 11 studies) provided information on crude rates in the non-HIV population (Supplementary Table 5).

A further 17 estimates from 16 studies were identified to estimate the pooled risk ratio of incident cardiovascular disease in individuals with HIV infection (Table, Figure 2b). Studies originated mainly from Europe, North America and Asia Pacific with few studies from low- and middle-income nations (Table) and primarily involving black and caucasian participants (Supplementary Table 6). The majority of studies used physician diagnosis or the international classification of disease coding system to define cardiovascular disease. The pooled risk ratio was 2·16 (95% CI 1·68 to 2·77) (Figure 2b). The risk ratio when stratified by type of event was 2·36 (95% CI 1·50 to 3·70) for any cardiovascular disease (including myocardial infarction and stroke), 1·79 (95% CI 1·54 to 2·08) for myocardial infarction and 2.56 (95% CI 1·43 to 4·61) for stroke. Risk ratios for older studies, those with moderate/high risk of bias and those with longer follow-up were larger (Supplementary Table 7). Selection bias due to potential unpublished studies or bias due to small-study effects was noticed for the overall risk ratio. Imputing for asymmetry using the trim and fill method did not alter the effect direction, but as expected, did attenuate the effect size (Supplementary Table 7 and Supplementary Figure 3). We observed substantial heterogeneity for the overall estimate (Figure 2).

Table.

Baseline Characteristics of Studies Providing Estimates of Risk Ratio

Author Cohort name Country Study type Data source Outcome classification % Male Age at baseline From To Outcome
Qureshi et al, 199726 Atlanta, Georgia USA CCS Clinical database ICD-9 58 35 1990 1994 Stroke†
Gardner et al, 200327 HERS USA Cohort study Hospital database NA 0 38 1993 2000 CVD*†
Cole et al, 200428 BW-CYSS USA Cohort study Clinical database ICD-9 83 35 1988 1991 Stroke†
Triant et al, 200929 RPDR USA Cohort study Clinical database ICD-9 63 38 1997 2006 MI†
Aldaz et al, 201130 Navarre Spain Spain Cohort study AIDS case register NA 68 NA 1999 2006 CVD* (Mortality)
Durand et al, 201131 Quebec Canada Cohort study Quebec public health insurance database and clinical database ICD-9 78 37 NA 2007 MI†
Chow et al, 201232 RPDR USA Cohort study Research Patient Data Registry ICD-9 69 42 1996 2009 Stroke (Incident) †
Helleberg et al, 201233 Danish HIV Denmark Cohort study Danish Civil Registration System, National registry of cause of death ICD-10 75.8 36 1995 2008 CVD* (Mortality)
Walker et al, 201334 Tanzania Tanzania CCS Verbal autopsy WHO definition 55 62 2003 2006 Stroke†
Mateen et al, 201335 MACS USA Cohort study MACS database ICD-9 100 41 1996 2011 Stroke
Tripathi et al, 201436 South Carolina Medicaid program USA Cohort study HIV reporting system Surveillance Database ICD-9 57 39 1994 2011 CVD*†
Womack et al, 201437 VACS-VC USA Cohort study MediCare/ IHD Quality Enhancement Initiative ICD-9 0 44 2003 2009 CVD* (Incident)
Sico et al, 201538 VACS-VC USA Cohort study MediCare/ IHD Quality Enhancement Initiative ICD-9/ICD-10 100 48 2003 2009 Stroke
Rasmussen et al, 201539∥ Danish HIV Denmark Cohort study Danish Civil Registration System, National registry of cause of death ICD-10 76 37 1995 2014 MI (Incident)
Althoff et al, 201540 VACS USA Cohort study MediCare/ IHD Quality Enhancement Initiative ICD-9 NA 48 2003 2010 MI†
Klein et al, 201541‡ KPNC KPSC USA Cohort study HIV registry; electronic medical record ICD-9 91 41 1996 2011 MI†
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Abbreviations: CCS – Case control studies; NA – Not available

*
CVD in the following studies defined as follows:
  • Gardner et al - Ischaemic heart disease, Cardiomyopathy, Ventricular arrythmias, Transient ischaemic attack, Congestive cardiac failure, Deep vein thrombosis, Stroke
  • Aldaz et al - ICD 10 codes from I00 to I99
  • Helleberg et al - ICD 10 codes from I00 to I99
  • Tripathi et al - Acute myocardial infarction, angina, percutaneous intervention and non-haemorrhagic stroke
  • Womack et al - Acute myocardial infarction, unstable angina, ischaemic stroke and heart failure
†

Outcome data determined from hospital databases and therefore may exclude fatal events occurring in the community and not resulting in hospitalisation

‡

Klein et al provided adjusted HR of 1.4 (95% CI 1.2 to 1.6) for the period of 1996-2011, however this risk estimate has decreased over time to 1.0 (955 CI 0.7 to 1.4) for 2010-2011

Helleberg et al provided the risk ratio for cardiovascular disease for the year of 1995 only comapared to an age- and sex-matched reference general population

∥

Rasmussen et al provided a risk ratio for both myocardial infarction and stroke

Figure 2. Forest plot.

Figure 2

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Pooled risk ratio for risk of cardiovascular disease in people living with HIV compared to those without stratified by type of event.

Both Aldaz et al30 and Helleberg et al33 evaluated cardiovascular mortality defined as an ICD code range from from I00 to I99

Trends in the global and regional burden of disease

Globally the population attributable fraction for cardiovascular disease associated with HIV infection increased from 0·36% (95% CI 0·21% to 0·56%) in 1990 to 0·92% (95% CI 0·55% to 1·41%) in 2015. This was associated with a >3-fold increase in disability-adjusted life years from HIV associated cardiovascular disease from 0·74 million (95% CI 0·44 to 1·16) in 1990 to 2·57 million (95% CI 1·53 to 3·92) in 2015 (Figure 3a). Similar temporal increases were seen when stratified by sex (Figure 3b, Supplementary Table 8).

Figure 3. Disability adjusted life years.

Figure 3

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Temporal change in the disability-adjusted life years (DALYs) of HIV associated cardiovascular disease globally (Figure 3A) and stratified by sex (Figure 3B); red line represents central estimate and blue dashed lines represent the 95% confidence interval.

Stack-plot showing the central estimate by UNAIDS region and time (Figure 3C).

There was marked regional variation in the temporal change in the disability-adjusted life years due to cardiovascular disease attributable to HIV (Figure 3c). In 2015, East and Southern Africa, Asia and the Pacific and West and Central Africa accounted for over two thirds of all disability-adjusted life years (Figure 3c). The largest annual increase across the 26-year period was observed in East and Southern Africa (15,870 disability-adjusted life years per year [95%CI 7,600 to 32,660]) with the lowest increases observed in the Middle East and North Africa (530 disability-adjusted life years per year [95%CI 280 to 950]) and Western and Central Europe and North America (700 disability-adjusted life years per year [95%CI 410 to 1,070]) (Supplementary Table 9).

National estimates

National estimates of prevalence and cardiovascular burden were available for 154 countries. The highest population attributable fraction was observed in countries within sub-Saharan Africa, with HIV accounting for more than 15% of the cardiovascular burden in Swaziland, Botswana, Lesotho and South Africa (Figure 4a, Supplementary Table 10). Similarly, the largest burden was observed in sub-Saharan Africa (Figure 4b). In the UNAIDS Global Plan priority countries, the population attributable fraction was comparable to other traditional cardiovascular risk factors (Supplementary Table 11).

Figure 4. Cartograms.

Figure 4

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Cartograms showing population attributable risk (Figure 4A) and HIV attributable disability-adjusted life years per 100,000 persons (Figure 4B) for HIV associated cardiovascular disease. Each colour category represents a septile.

Data for the burden of cardiovascular disability-adjusted life years attributable to HIV were available for 20 of the 21 priority countries from sub-Saharan Africa in the UNAIDS Global Plan.22 HIV associated cardiovascular disability-adjusted life years across these countries increased from 0·21 million (95% CI 0·11 – 0·38) in 1990 to 0·74 million (95% CI 0·39 – 1·37) in 2015 (Supplementary Figure 4).

Discussion

In this systematic review, meta-analysis and burden assessment, we evaluated the association between HIV infection and cardiovascular disease, and estimated the national, regional and global burden of cardiovascular disease attributable to HIV infection. We make a number of important and novel observations. First, the crude rate for incident cardiovascular disease was 60 per 10,000 person years and is comparable to other high-risk cardiovascular groups, such as diabetes mellitus.42 Second, the risk of incident cardiovascular disease was 2-fold higher in people living with HIV. Third, the number of disability-adjusted life years due to HIV associated cardiovascular disease has increased 3-fold over the last two decades but has now plateaued. Finally, there were major regional variations in both the attributable fraction and the rates of cardiovascular disease due to HIV, with much of the burden seen in sub-Saharan Africa followed by Asia and the Pacific.

Many factors may have affected the estimates that we have derived and are based on several assumptions that merit discussion. First, the pooled risk ratios used to calculate the population attributable fraction and the subsequent cardiovascular burden were primarily obtained from developed nations but were applied to all regions. This approach is ubiquitous in these types of analysis43, 44 and highlights the paucity of data from these regions. In a recent analysis evaluating the global burden cardiovascular disease attributable to hypertension and obesity less than 10% of cohorts originated from low- and middle-income nations.44, 45 Second, the incidence rate does not consider competing risk from non-cardiovascular mortality. This would further underestimate the rate of cardiovascular disease in people living with HIV especially in earlier studies where anti-retroviral therapy was not widely available. Third, whilst many of the individual studies evaluating the risk ratio of cardiovascular disease adjusted for important traditional risk factors, there remains the risk of residual confounding. Previous studies have already shown higher frequency of both modifiable and non-modifiable cardiovascular risk factors in people living with HIV.17 As such, higher prevalence of factors that do not lie on the causal pathway, may have influenced the overall association between HIV and cardiovascular events. Fourth, the pooled relative risk estimates used to calculate the population attributable fraction for DALY for ischaemic heart and cerebrovascular disease, was obtained solely from studies including acute myocardial infarction or stroke and so did not specifically include estimates for angina pectoris or other chronic manifestations of atherosclerotic disease. However, relative to the overall cardiovascular DALY attributable to ischaemic heart disease the burden from angina is minimal.10 Therefore, the impact of this limitation on the overall burden estimate is likely to be small. Fifth, the majority of studies evaluating the risk of cardiovascular disease in people living with HIV have recruited participants before 2010, with a large number conducted in the previous century. The epidemiology of HIV diagnosis and care has changed significantly over the last two decades with better provision of anti-retroviral therapy and improved survival resulting in an increased prevalence of HIV.46 Sixth, when calculating the burden at a global and regional level we have made the assumption that the prevalence of HIV infection in the younger age group (15 to 49-year-old) is consistent across the entire age range. There is a paucity of data in the prevalence of HIV in the older population especially in high-prevalent regions such as sub-Saharan Africa.47 However, analysis of the populations in these regions show that the prevalence in the older population remains similar to that of the 15-49 years.47 Finally, we noticed substantial heterogeneity for our overall pooled risk ratios. The source for this degree of heterogeneity is likely to be multifactorial and reflect differences in population demographics, sample size and small study effect, patient characteristics, selection or publication bias and case ascertainment bias as the majority of data was based on national statistics.

Many studies have evaluated the association between HIV infection and the risk of atherosclerotic disease including the potential role of anti-retroviral therapy.17, 48–50 This is the first study to review and to meta-analyse systematically the association between HIV infection and cardiovascular disease, and estimate the burden of cardiovascular disease attributable to HIV. The mechanisms underlying this association remain poorly understood.17 Possible mechanisms include endothelial dysfunction51 and increased systemic13 and coronary arterial inflammation14 associated with elevated inflammatory markers.13 Furthermore, patients with HIV have more traditional metabolic risk factors for cardiovascular disease17 including dyslipidaemia,15 insulin resistance and abnormal glucose homeostasis,16 and abnormalities in body-fat composition.52–54 The increased risk of cardiovascular disease in people living with HIV is thus a consequence of both accelerated atherosclerosis due to chronic infection and the increased prevalence of traditional risk factors.

The global burden of cardiovascular disease attributable to HIV infection has tripled over the last two decades especially in the low- and middle-income nations, and is likely to be a product of both temporal increases in the prevalence of HIV, and the morbidity and mortality of cardiovascular disease. The prevalence of HIV varies by region with the greatest proportions seen in sub-Saharan Africa and Asia Pacific. Cardiovascular disease now accounts for over 10% of all morbidity and mortality in sub-Saharan Africa with rates that are comparable to high-income regions. Consequently, the sub-Saharan region accounted for half of all disability-adjusted life years from cardiovascular disease attributable to HIV. The population attributable fraction of HIV associated cardiovascular disease in the UNAIDS high-priority countries was up to 25% and similar to traditional lifestyle, metabolic and environmental risk factors.23, 24

The combined burden of HIV and cardiovascular disease in the UNAIDS high-priority countries is of growing concern and has important implications with respect to regional health policies, guidelines and resource allocation. Risk stratification and identification of patients at intermediate or high risk of future cardiovascular disease are already challenging in resource limited nations.55 Furthermore, traditional risk scores perform poorly because they consistently underestimate risk in HIV infected populations.35, 56, 57 Whether patients living with HIV should be considered high risk and started on primary prevention, such as statin therapy, remains unclear. A recent randomised controlled trial of rosuvastatin in patients with HIV demonstrated a reduction in carotid artery intima–media thickness despite these individuals having low LDL cholesterol concentrations at baseline.58 Whilst the latest international guidelines have expanded the use of lipid lowering therapy in the general population, over two-thirds of people living with HIV with evidence of high-risk morphology coronary atherosclerotic plaque would not have been recommended for statin therapy.59 The Randomised Trial to Prevent Vascular Events in HIV (REPRIEVE) study is now underway to evaluate the efficacy of statin therapy in people living with HIV who are deemed low-risk based on traditional risk scores.60, 61

Conclusions

This analysis evaluates the association between HIV and cardiovascular disease, and estimates the global burden of HIV associated cardiovascular disease. We report that the risk of cardiovascular disease was 2-fold higher in people living with HIV. Moreover, the global burden of HIV associated cardiovascular disease has tripled over the last two decades and is now responsible for 2.6 million disability-adjusted life years per annum with the majority in sub-Saharan Africa and the Asia Pacific regions. Our estimates have important policy implications for implementing appropriate cardiovascular risk stratification and treatment strategies across healthcare systems especially in those countries with the greatest burden where resources remain limited.

Supplementary Material

Supplemental Material

Clinical Perspective.

What Is New?

  • Recent studies have identified plausible biological mechanisms, including endothelial dysfunction and arterial inflammation, to explain the association between HIV infection and atherosclerotic disease.

  • This manuscript represents a systematic analysis to evaluate the association between HIV and cardiovascular disease and estimate the burden of HIV associated cardiovascular disease at a national, regional and global level.

  • We report that the risk of cardiovascular disease is increased 2-fold in people living with HIV and the global burden of HIV associated cardiovascular disease has tripled over the last two decades with the majority of the burden experienced in sub-Saharan Africa and the Asia Pacific regions.

What Are the Clinical Implications?

  • The combined burden of HIV and cardiovascular disease, especially in high prevalent regions, has important implications with respect to regional health policies, guidelines and resource allocation.

  • Risk stratification and identification of patients at risk of future cardiovascular disease is already challenging in these regions.

  • Whether patients living with HIV should be considered high risk and implemented on appropriate primary prevention pharmacotherapy such as statin therapy remains unclear.

  • Our estimates have important policy implications for implementing appropriate cardiovascular risk stratification and treatment strategies across healthcare systems especially in low- and middle-income nations where both HIV and cardiovascular disease remain highly prevalent.

Sources of Funding

This research was funded by the British Heart Foundation with NLM and DEN supported by the Butler Senior Clinical Research Fellowship (FS/16/14/32023) and John Wheatley Chair (CH/09/002) awards respectively. DM is funded via an Intermediate Clinical Fellowship and Beit Fellowship from the Wellcome Trust (201492-Z-16-Z).

Footnotes

Disclosures

None.

Contribution Statement

ASVS conceived the design and carried out the initial acquisition, analysis, and interpretation of data. All authors were involved in drafting the manuscript and revising it, and have given final approval of the version to be published.

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