APLICACIÓN DE NORMAS Y REGLAMENTOS ANR 7,

101 cardiovascular risk in persons on ART especially the PI based one^17,19,35. Reasons suggested for this is that HIV and ART may have an additional influence on traditional CHD risk factors³⁵. However, it is generally agreed that knowing the CHD risk and acting on it is imperative to long term survival in HIV infected persons.

102 mortality in HIV infected persons and have been associated with hypertension and the use of protease inhibitors113,166,167.

Echocardiographic abnormalities were present in 76.0% of the HIV infected subjects, this comprised of 73.3% of those on ART and 80.0% of those not on treatment. The findings were comparable to that obtained by Danbauchi et al¹¹⁴ in Zaria where 75% of treatment naive patients studied had echocardiographic abnormalities. Similarly Olusegun-Joseph et al in Lagos reported a prevalence of 78.0% also in treatment nạve patients¹¹⁵. However in a study by Hakim et al¹⁶⁸ in Zimbabwe, echocardiographic abnormalities were found in 50% of patients studied who were however on anti-retroviral therapy.

The commonest echocardiographic abnormalities were pericarditis (thickened pericardium), left ventricular dysfunction and pericardial effusion. In this study, pericarditis was found in 46.0% of the subjects with 30.0% having moderate pericardial effusion. Some echocardiographic surveys have established that pericardial disease with or without effusion is a common finding in HIV infected persons. Pericardial disease has not been correlated with any clinical stage of HIV disease;

it has also been associated with shortened survival independentof CD4 count^122-125. The prevalence at echocardiography ranges from 10–59%⁸⁸ although majority of these are asymptomatic. Cases of massive effusion with cardiac tamponade, and constrictive pericarditis have also been reported^98,122,125. In Africa, tuberculosis is the major cause of large pericardial effusion¹²⁵. Pericardial diseases can be caused directly by the virus⁹⁸, involvement of opportunistic infections such as mycobacterium¹³⁰, malignancy such as Kaposi Sarcoma¹³¹ and non Hodgkin Lymphoma¹²², or be part of a generalized effusive serous process probably as a consequence of enhanced cytokine expression¹²². Small asymptomatic pericardial effusion canspontaneously resolve in HIV patients, however, the frequency of resolution varies. In a studyby Blanchard et al¹⁰⁶, 42% of the patients studied had spontaneous resolution of their effusion, while in another study by Heidenreich et al¹²², only 13% had spontaneous resolution. Mortality, however, remains increased in HIV infected

103 patients who develop an effusion,even if the effusion resolves over time^100,122. In a study in Lagos Nigeria, Olusegun-Joseph et al¹¹⁵ found moderate pericardial effusion in 47% of one hundred treatment nạve HIV infected subjects studied.

Left ventricular systolic and diastolic dysfunctions are common echocardiographic findings among HIV infected persons. Left ventricular diastolic dysfunction was found in 36.0% and systolic dysfunction in 34.0% in this study. The findings confirm that HIV infection is associated with left ventricular dysfunction and increased ventricular dimension. Similar trends had been noted in other studies^89,91-99. However, the presence of ventricular dysfunction in the absence of chamber enlargement as found in some in this study have also been reported in other studies103-107,113. This has been suggested to represent an early phase of cardiomyopathy106,107,113. Systolic dysfunction as noted in 34% of the subjects signifies reduced myocardial contractility. It is a frequently documented finding in echocardiography of HIV positive patients^87,91,93. Comparable findings has been reported by Silva-Cardoso et al⁹¹ in a study that recruited 98 HIV positive patients in Portugal where systolic dysfunction was found in 32.0% of subjects investigated. The dysfunction was also noted to be worse with disease progression. Most of the patients in that study were also asymptomatic, only 8.0% of the total number of cases studied had symptomatic heart failure. Hecht et al⁸⁷ in a similar study involving 27 homosexual AIDS patients, and 21 negative homosexuals as controls, reported systolic dysfunction in 30% of cases, and in 5% of controls. In Zaria, Danbauchi et al¹¹⁴ reported systolic dysfunction in 19 of 40 patients with stage III/IV HIV/AIDS (47.5%). The higher prevalence in this study was expected since most of the patients studied were in the advanced stage of the clinical spectrum. In Lagos, Nigeria Olusegun-Joseph et al¹¹⁵, reported systolic dysfunction in 30% 0f 100 treatment nạve patients studied.

Systolic dysfunction is said to be an important cause of morbidity and mortality in AIDS patients¹⁰⁹. It is also said that symptomatic heart failure will occur in approximately 6% of these patients, especially at the end stage of the disease⁹⁴. With this in mind, early recognition of cardiac

104 dysfunction and institution of management should impact on the overall outcome of these patients⁹³.

Diastolic dysfunction as noted in 36% of the subjects signifies progressive ventricular filling abnormality due to a non compliant ventricle^164. The findings of this study compares with the 30%

prevalence noted by Danbauchi et al¹¹⁴ and 32% by Olusegun-Joseph et al¹¹⁵ in their respective studies. Silva-Cardoso et al⁹¹ however reported diastolic dysfunction in 63% of their study population. Longo-Mbenza et al¹¹¹ from Congo in a study involving 49 HIV positive patients and 58 controls, reported diastolic dysfunction in 85.7% of the subjects and none in the controls. The pathogenesis of left ventricular diastolic dysfunction in HIV infected patients is unknown¹¹¹. Possible etiologies includedirect infection of the heart by the HIV virus and other opportunistic pathogens with resultant myocarditis, or direct involvement by a neoplastic process^111.

Generally left ventricular dysfunction confers a bad prognosis in affected persons, it has been reported that the median survival is 101 days in HIV infected persons with left ventricular dysfunction, as against 476 days of survival in patients with normal heart analysed by echocardiography at similar infection stage¹⁴.

Dilated cardiomyopathy occurs at an increased rate in the setting of HIV infection11,12,93,97,98. It was found in 6% of the subjects in this study all of whom had detectable viral loads and CD4 counts less than 200 copies/ml. Other authors have linked dilated cardiomyopathy in HIV infected persons to very low CD4 counts and markedly elevated viral loads93,107-110,115,133. A study in Lagos by Olusegun-Joseph et al¹¹⁵ in 100 HIV infected treatment nạve subjects reported a prevalence of 5%

all of whom had CD4 count less than 100 copies/ml. In another study in Cameroon, Nzuobotane et al⁹³ reported a relationship between low CD4 count and the likelihood of cardiomyopathy. Also Currie et al¹⁰⁹ in a similar study involving 296 HIV positive patients in Britain, reported a prevalence of about 4% and association with CD4 count less than 100 cells/ml.

105 Hakim et al¹⁶⁸ in a study in Zimbabwe reported a prevalence of 9%, most of who were in the advanced stage of the disease. Himelman et al¹⁰⁵ in their study reported a prevalence of 11% of the 70 HIV positive subjects studied. Corallo et al¹⁰⁷ on the other hand reported a rate of 17.6% of 102 subjects, however the subjects had advanced disease hence the higher prevalence in the study.

Barbaro et al⁹⁷ in an prospective clinical and echocardiographic follow-up study of 952 asymptomatic HIV positive patients reported dilated cardiomyopathy in 76 patients (8%), with a mean annual incidence rate of 15.9 cases per 1000 patients. They concluded that dilated cardiomyopathy may be related either toa direct action of HIV on the myocardial tissue or to an autoimmuneprocess induced by HIV, possibly in association with other cardio-tropicviruses, and that the extent of the immunodeficiency of the patients had a major role in the development of cardiomyopathy.

Some studies have indicated that the prognosis and survival of patients with HIV who develop dilated cardiomyopathy is poor^97,109. Currie et al¹⁰⁹ noted that the median survival is 101 days for those with cardiomyopathy, as compared with 472 days in patients with normal hearts on echocardiogram who are at a similarstage of disease, confirming the clinicalimportance of cardiac dysfunction in the outcome of HIV infectedpatients.

Nutritional factors have also been linked with dilated cardiomyopathy in HIV positive patients.

Deficiency of selenium and other trace elements have been associated with dilated cardiomyopathy in these patients^12,13,. Selenium deficiency as a causeof HIV related heart muscle disease may be of considerable interest in Africa where patients often present with multiple nutritionaldeficiencies, prolonged diarrhoea, and wasting, which may involve selenium deficiency⁹³. Selenium supplementation has been shown to improve cardiac dysfunction in these patients12,13,88,98. Also cardiotoxic effect of antiretroviral drugs such as Zidovudine have also been implicated in HIV cardiomyopathy^94,97.99.

5.04 Independent Predictors of specific Cardiovascular Abnormalities in the Subjects

106 In addition to evaluating the cardiovascular abnormalities found in HIV infected patients, this study also set out to look at the relationship i.e. independent predictors between HIV parameters (duration since HIV diagnosis. ART duration, CD4 count and Viral load) and specific cardiovascular abnormalities found in the subjects.

For hypertension, the duration of HIV infection and duration of ART on univariate analysis showed strong association to the presence of hypertension in the subjects. This was expected because these factors predisposes the subjects to vasculopathy, neuropathy and nephropathy which may also cause hypertension in the subjects12,13,88,98. However, when this relationship was further tested in a multiple logistic regression model; neither of these factors emerged as independent predictor of hypertension in the subjects. This finding may have been influenced by other factors such as sample size. Some authors have identified increased duration of HIV infection and anti-retroviral therapy as independent predictors of hypertension in HIV infected persons16,17,35,44,47-49.

Similar trend was also observed for left ventricular hypertrophy whereby there was a strong association to duration of HIV infection and anti-retroviral therapy on univariate analysis which was not sustained in a multiple logistic regression model perhaps for similar reasons as above.

Literature search however revealed that these factors have been identified by some other authors as independent predictors of left ventricular hypertrophy in the subjects^94,96.

With regards to left ventricular dysfunction, none of the factors studied showed significant association on univariate analysis. However some studies have reported significant association of left ventricular dysfunction with low CD4 count and increased viral load in HIV infected persons^94,96. The virus is known to be cardio-toxic and may cause alterations in cardiac structure and functions in infected persons94,97,106,107,113.

Dilated cardiomyopathy was found in 6% of the subjects in this study; on univariate analysis CD4 count of less than 200 cells/ml and viral load greater than 200 copies/ml were found as significant associations. However on multivariate analysis, the relationships were not sustained. Low CD4

107 count and increased viral loads have been identified by some authors as independent predictors of dilated cardiomyopathy in HIV infected persons93,107-110,115,133. The finding in this study may have been influenced by other factors.

Evaluation of subjects with pulmonary hypertension in this study did not show a statistically significant factor on univariate analysis. Some authors have opined that primary pulmonary hypertension in HIV infected persons is not associated with HIV stage, viral load and CD4 counts^12,118,119.

Pericardial disease was found in 46% of the subjects, 30% of the subjects also had moderate pericardial effusion. On univariate analysis CD4 count less than 200copies/ml was identified as a significantly associated factor. The relationship was sustained in a multiple logistic regression model. Low level of immunity as represented by CD4 count less than 200 copies/ml predisposes HIV infected patients to opportunistic infections which can manifest as pericarditis with or without effusion. This is in agreement with findings by other authors115,122-125. Some have gone as far as postulating that the presence of an effusive pericarditis in a subject connotes a bad prognosis and is an indicator of a much weakened immune system115,122-125. Hence the need to urgently investigate and treat whenever it’s found in HIV infected patients.

Metabolic syndrome is a constellation of specific cardiovascular risk factors. The duration of HIV infection and antiretroviral therapy were identified as significant factors on univariate analysis but none was sustained in a multiple logistic regression model. Some studies have however identified these as independent predictors of metabolic syndrome44,60,66,67. This is expected because HIV and antiretroviral therapy adversely affect the metabolic state of the human body and metabolic syndrome may be a direct consequence of this.

The presence of an abnormal electrocardiogram in the HIV infected person may suggest an underlying cardiac disease. In this study, the HIV parameters studied i.e. duration of HIV and antiretroviral therapy, CD4 count less than 200 cells/ml and detectable viral loads were identified as

108 significant factors associated with abnormal electrocardiogram in the subjects. However in a multiple logistic regression model, detectable viral load emerged as an independent predictor of presence of an abnormal electrocardiogram in the subjects. HIV particles are directly cardio-toxic^97,107 and when significantly elevated may cause abnormalities in the electrical and mechanical systems of the heart. Other authors have reported similar findings and have gone ahead to infer that it confers a bad prognosis for the patients^144-150.

The presence of moderate-high Framingham risk score was associated with the duration of HIV infection and antiretroviral therapy on univariate analysis in the subjects. This is expected because the virus and antiretroviral drugs can have an adverse effect on body metabolism and hence the various components of the risk score. Elevated Framingham risk scores connote a bad prognosis for the patients as they may go on to have a cardiovascular event. However in a multiple logistic regression model, these relationships were not sustained perhaps due to other factors. Findings by other authors have identified these factors as independent predictors of elevated Framingham risk scores in HIV infected persons16-20,79-84.