Acute coronary syndromes in black South African patients with human immunodeficiency virus infection
Year: 2011
Type: dissertation
Study design: Observational Study
Abstract: Background: South Africa is considered to be a country in epidemiologic transition with \nincreasing rates of cardiovascular disease. In addition, it faces an HIV pandemic, with an \nestimated 5.5 million people infected and five hundred thousand HIV-related deaths \nannually. Current evidence suggests that patients infected with HIV are at a heightened \nrisk for acute coronary syndromes (ACS) related to traditional cardiovascular risk factors, \nas well as factors related to the virus and its treatment (highly active anti-retroviral \ntherapy (HAART)). HIV infection itself may independently predispose to coronary artery \ndisease (CAD) by promoting endothelial dysfunction, a heightened pro-inflammatory \nstate, dyslipidaemia and thrombosis, the aetiology of which is thought to be multifactoral \nin nature. \nProtease inhibitor (PI) therapy, as part of HAART, has the potential to induce an adverse \nmetabolic phenotype, including: dyslipidaemia, insulin resistance, endothelial dysfunction \nand a prothrombotic state. The attributable risk of these factors in HIV-associated CAD \nand ACS is currently unknown, but it seems that the risk of ACS is increased by \nprolonged exposure to PI’s. No data currently exists on CAD in HIV patients not \nreceiving HAART, which is problematic considering that this makes up the majority of \npatients in sub-Saharan Africa and that the combination of epidemiologic transition and \nHIV infection has the potential for greater cardiovascular morbidity, particularly with \nrespect to atherothrombotic events. \nviii \nAims: The aims of this thesis are twofold. Firstly, to confirm reports of epidemiologic \ntransition in South Africa from a broad epidemiological perspective. Secondly, by focusing on \ntreatment-naïve HIV positive black South Africans with ACS, it aims to determine differences \ncompared to HIV negative patients with respect to demographics and risk factors, \nangiographic and treatment related factors as well as markers of thrombosis and inflammation \nwith a view to providing more focused primary and secondary prevention. \nMethods: All the studies contained in this thesis were conducted in the Department of \nCardiology, Chris Hani Baragwanath Hospital and adhere to the declaration of Helsinki. The \nfirst of the epidemiological studies, The Heart of Soweto (HOS) study (Chapter 3), was a \nprospectively designed registry that recorded epidemiologic data relating to the presentation, \ninvestigations and treatment of 1593 patients from Soweto with newly diagnosed \ncardiovascular disease during the year 2006. The second study (Chapter 4) was a cross \nsectional study of patients with ACS admitted to the Baragwanath coronary care unit over the \nyear 2004 compared to the years 1975-1980. \nThe HIV sub-study (chapters 5-8) was a prospective single centre study conducted from \nMarch 2004 to February 2008. During this time, 30 consecutive black HIV patients \npresenting with ACS (ACS+: HIV+ group) were enrolled. For each HIV patient with \nACS, the first presenting non-HIV black patient with ACS was selected as a case control \ncomparator (ACS+ : HIV- group). In addition, a second control group of 30 asymptomatic \nHIV patients, who were matched for age, sex and ethnicity (ACS- : HIV+ group), were \nrecruited from the HIV clinic. The methodology used to compare the groups involved: \nclinical and demographic data collection, routine blood test evaluation, angiographic \nix \nanalysis and specific laboratory testing of various research blood parameters (including \nthrombotic screening and markers of inflammation and endothelial activation). \nResults: Chapter 3 presents the results of the large HOS study, which showed good \nevidence to support the theory of epidemiologic transition in Soweto. Adding to this data \nare the results of Chapter 4, which clearly demonstrate a substantial increase in the \nnumber of patients diagnosed with ACS at Baragwanath in recent years. Consistent with a \npopulation in epidemiologic transition, there was more than a ten-fold increase in the rate \nof coronary events over two decades, paralleled by increased rates of modifiable risk \nfactors. Chapter 5 presents the clinical and angiographic data from the HIV sub-study. \nHIV patients with ACS were younger and had fewer traditional risk factors for CAD \nexcept for higher rates of smoking and lower HDL cholesterol levels. HIV patients had \nless atherosclerotic burden angiographically, but a higher thrombus burden in the infarct \nrelated arteries, suggesting a possible prothrombotic state. In addition, HIV patients had \nhigher rates of in-stent restenosis of bare metal coronary stents at follow up. Chapters 6 \nand 7 present data on the thrombotic parameters between the groups, with Chapter 6 \nfocusing mainly on coagulation pathways and Chapter 7 focusing on antiphospholipid \nantibodies (aPL). Chapter 8 presents data on levels of pro-inflammatory cytokines and \nendothelial activation markers. Greater evidence of thrombophilia was found in HIV \npatients with ACS as evidenced by lower Protein C (PC) levels, higher levels of Factor \nVIII and a higher inflammatory burden with greater degrees of endothelial cell activation \n- all of which increase thrombotic risk. Antiphospholipid antibodies were more prevalent \nin HIV patients but did not seem to be causal in the pathogenesis of thrombosis. \nx \nConclusion: Soweto, a large, predominantly black urban area in South Africa, is in a state of \nepidemiologic transition, with an increasing prevalence of modifiable cardiovascular risk \nfactors and ischaemic heart disease. Treatment-naïve HIV positive black patients presenting \nwith ACS have different clinical and angiographic features compared to the HIV negative \npopulation. The patients are younger, more commonly male, with high rates of smoking, lower \nHDL levels and less atherosclerotic burden. However, there is a higher thrombotic burden, \nsuggesting a prothrombotic state, which was evident by lower PC levels, higher factor VIII \nlevels with a higher inflammatory burden and a greater degree of endothelial cell activation – \nall factors associated with a pro-atherogenic and prothrombotic state. The exact pathogenic \nrole of HIV, independent of associated modifiable and non-modifiable risk factors, is difficult \nto determine, but may be important as a contributory factor in an already “vulnerable” patient. \nImportantly, we identified modifiable risk factors in the HIV group. Smoking may play a \ncrucial role in the pathogenesis of ACS in these otherwise seemingly low risk patients and \nremains an important target for cardiovascular risk reduction. \nThe role of HDL in the pathogenesis and prevention of HIV-associated CAD needs to be \nfurther defined, as does the role of drug eluting coronary stents in the prevention of in-stent \nrestenosis. Cardiovascular risk assessment and appropriate primary prevention should be an \nimportant component in the management of HIV patients, regardless of treatment status. With \nthe anticipated increase in CVD in South Africa, further research projects appropriate to the \nSouth African context will be vital in order to explore cost effective ways to provide primary \nand secondary prevention in order to effectively deal with the burden of epidemiological \ntransition as well as the cardiovascular burden likely to be imposed by the HIV pandemic.
Author: Anthony Becker
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2169905990