|Year : 2019 | Volume
| Issue : 1 | Page : 11-17
Relationship between CD4 cell count and left ventricular dimension and function in treatment-naïve human immunodeficiency virus-infected patients
Alaba Philip Adebola1, Akindeji A Akinbo2, Folashade A Daniel3
1 Department of Medicine, Division of Cardiology, LASUTH/LASUCOM, Lagos, Nigeria
2 LASUTH, Lagos, Nigeria
3 LASUTH/LASUCOM, Lagos, Nigeria
|Date of Submission||19-Apr-2019|
|Date of Decision||12-Jun-2019|
|Date of Acceptance||15-Jul-2019|
|Date of Web Publication||22-Oct-2019|
Dr. Alaba Philip Adebola
Department of Medicine, Division of Cardiology, LASUTH/LASUCOM, Ikeja, Lagos
Source of Support: None, Conflict of Interest: None
Introduction: Echo studies have documented obvious changes in the left ventricular (LV) dimension and function of human immunodeficiency virus (HIV)-infected patients. Previous studies had suggested that patients with very low CD4 cell counts (≤200/μl) were more likely to be at risk of cardiac complications. The aim of the present study was to evaluate and correlate the LV dimension and function of treatment-naïve HIV-positive patients with their CD4 cell count.
Methodology: A total of 100 consenting treatment-naïve HIV-infected patients and fifty healthy controls were recruited for this study. The data were analyzed using the Statistical Package for the Social Science version 20.0. The data were subjected to appropriate statistical tests. The statistically significant P value was set at 0.05.
Results: Fifty-eight HIV-infected patients had CD4 cell count of >200/μl, whereas 42 had CD4 cell count of ≤200/μl. A higher proportion of treatment-naïve HIV-infected patients had larger LV dimension compared to their healthy seronegative counterparts (P = 0.01). The HIV-infected patients were more likely to have asymptomatic systolic and diastolic dysfunctions compared to the healthy seronegative adults (P = 0.01). Thirty-three HIV patients had LV systolic dysfunction consisting of 26 (61.9%) with CD4 cell count <200/μl and 7 (12.1%) with CD4 cell count >200/μl. Thirty-four of the patients had LV diastolic dysfunction consisting of 20 (47.6%) with CD4 cell count <200/μl and 14 (24.1%) with CD4 cell count >200/μl. The LV cavity diameter and LV mass index did not show any significant correlation with CD4 cell count ([r] = −0.018; P = 0.863 and [r] =0.012; P = 0.902, respectively). LV systolic function showed significant positive correlation with CD4 cell count, (r = 0.384; P = 0.001).
Conclusion: Treatment-naïve HIV-infected patients had larger LV dimension and were more likely to have LV systolic and diastolic dysfunction compared to HIV-negative healthy individuals. Some of these findings were more prevalent in HIV-infected patients with very low CD4 cell count of ≤200/μl.
Keywords: CD4 cell count, echocardiography, treatment-naïve human immunodeficiency virus patients
|How to cite this article:|
Adebola AP, Akinbo AA, Daniel FA. Relationship between CD4 cell count and left ventricular dimension and function in treatment-naïve human immunodeficiency virus-infected patients. Nig J Cardiol 2019;16:11-7
|How to cite this URL:|
Adebola AP, Akinbo AA, Daniel FA. Relationship between CD4 cell count and left ventricular dimension and function in treatment-naïve human immunodeficiency virus-infected patients. Nig J Cardiol [serial online] 2019 [cited 2020 Jul 10];16:11-7. Available from: http://www.nigjcardiol.org/text.asp?2019/16/1/11/269654
| Introduction|| |
Human immunodeficiency virus infection/acquired immunodeficiency disease (HIV/AIDS) is a multisystem disease affecting virtually every organ and system of the body. A wide range of cardiovascular diseases have been identified in patients with HIV/AIDS. The spectrum ranges from myocardial diseases to pericardial, endocardial disease, coronary artery disease, malignancies, vascular disease, cardiac arrhythmias, and autonomic dysfunction.,,, The exact prevalence of cardiac involvement in HIV/AIDS is uncertain. However, some workers put the prevalence at a conservative estimate of between 2% and 10%. Cardiac involvement in HIV infection is multifactorial and may arise as a result of myocardial invasion with HIV itself, opportunistic infections, viral infections, autoimmune response to viral infection, highly active antiretroviral therapy (HAART)-related cardiac toxicity, nutritional, and trace element (selenium) deficiencies.,,
Previous studies have documented obvious changes in the left ventricular (LV) dimension on echocardiography (echo) in HIV-positive patients.,, These changes include a progressively dilated left ventricle and increased LV mass/hypertrophy. HIV-associated cardiomyopathy has been shown to be associated with advanced immunosuppression and lower CD4 lymphocyte counts and is independently associated with deaths.,,, Other previous studies suggest strong correlation between low CD4 count of <200/mm3 and the prevalence of HIV-associated cardiac diseases.,,
The reported prevalence of LV dysfunction in HIV infection from several studies in Europe and America, varies from 2% to over 40%.,, Studies from Africa and Nigeria also revealed that ventricular dysfunction is not uncommon in HIV/AIDS patients.,, However, only few studies compared the relationship between CD4 cell count and LV function. The study was aimed at evaluating the relationship between the CD4 cell count and LV dimension and function in treatment-naïve HIV-positive patients attending the LASUTH HIV clinic.
| Methodology|| |
This study was an observational descriptive and case-control study. The sample size was based on estimated prevalence rate of HIV infection in Nigeria of 4.1% and at least a 20% provision for attrition rate. A total of 100 consenting treatment-naïve HIV-positive patients attending the HIV clinic of LASUTH, were recruited into the study by systematic random sampling method. This sample size was comparable to a similar study done in Nigeria. Fifty apparently healthy, HIV-negative individuals were recruited from members of the hospital community as the controls. Individuals who were known hypertensive, on antihypertensive drugs, had blood pressure (BP) ≥140/90 mmHg, diabetic, had a history of excess alcohol intake (>3 units/day), had clinical odds ratio (OR) echo evidence of other underlying structural heart diseases, were all excluded from the study.
Interviewer structured questionnaire was administered to all patients, to obtain sociodemographic information such as age, sex, occupation, educational status, alcohol, and smoking history. The history that could suggest underlying cardiac disease such as dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, palpitations, chest pain, and leg swelling were also obtained. Patients had clinical evaluation of their pulse, BP, cardiac status, weight, height, and calculated body mass index, based on recommended standards.
CD4 cell count was measured in all patients and patients were categorized according to those who have ≤200/μl and those with >200/μl of CD4 cell count. Previous studies had suggested that patients with CD4 count of <200/μl was associated with increased prevalence of HIV-associated cardiovascular disease.,, This was taken into consideration in the analyses of the results. CD4 cell counts of all patients were measured at LASUTH HIV clinic by flow cytometry, using counter 2 machines, with 5 ml of blood drawn in ethylenediaminetetraacetic acid tube following the standard procedure as well as observing universal precautions.
Echocardiographic examinations were carried out using a general electric vivid Q imaging system device (GE Ultrasound AS, Horten, Norway) equipped with a 3.5 MHZ transducer probe and the procedure was based on the recommendation of the American society of echocardiography., The LV dimension such as the LV cavity diameter (LVIDd) in diastole and systole, LV free wall thickness in diastole (posterior wall and interventricular septum) were measured directly by the leading edge to leading-edge method. The LV mass was calculated using the Devereux and Reichek formula, i.e., LVM = 0.8 (0.4) ([LVEDD + IVSD + PWD]3–[LVEDD] 3) +0.6 g/m2. The LV mass was subsequently indexed on the body surface area, i.e., LV mass index (LVMI) = LVM/BSA. The body surface area was derived from the Mosteller equation. The relative wall thickness (RWT) was derived from the appropriate formula. The derived ejection fraction (EF) was based on the Teichholz et al. formula. The LV fractional shortening (FS) was derived by the echo machine based on standard formula, i.e., FS = LVEDD-LVESD/LVEDD × 100 (%).
The parameters for LV systolic function were based on the LV ejection fraction (LVEF) and fractional shortening (LVFS) while that of diastolic function was based on mitral E/A pulse wave, deceleration time (DT), and isovolumetric relaxation time (IVRT) diastolic flow patterns on Doppler echo. The following were the operative definitions for abnormal echo parameters: (1) Dilated left ventricle was defined as LVIDd > 5.2 cm. (2) Patients with LV LVMI >125 mg/m2 for male and >110 mg/m2 for female were classified as having LV hypertrophy. (3) Patients with septal/posterior wall thickness ratio ≥ 1:3 were classified as having asymmetric septal hypertrophy. (4) Patients with RWT >0.43 were classified as having increased RWT. (5) Patients with LVEF <50%, were classified as having LV systolic dysfunction., (6) LV diastolic dysfunction was diagnosed in the presence of any of the following criteria on pulse wave Doppler: Impaired relaxation with an E/A ratio <1, IVRT >100 ms or DT >220 ms, Pseudo normalization resembling the normal configuration with respect to the mitral inflow but with normal or low DT and restrictive pattern with E/A ratio of >2, IVRT <70 ms and DT <160 ms.
The data were analyzed using the Statistical Package for the Social Science version 20.0. Continuous data were presented as mean and standard deviation with independent Student t-test used to compare two means.
Analysis of variance was used to compare more than two means, and least significant difference post hoc analysis was used for pairwise relationship. Categorical variables were presented as percentages, whereas Chi-square and Fisher's exact tests were used to find association between categorical variables.
Pearson's coefficient was used to find the correlation between CD4 cell count and LV dimension and function. The statistically significant P value was set at 0.05.
| Results|| |
The patients sub-population comprised 67 females (67.0%) and 33 males (33.0%), whereas the controls included 33 females (66.0%) and 17 males (34.0%). The gender distribution was similar (χ2 = 0.015; P = 0.903). The CD4 cell count results ranged from 21.00 to 987.00/μl with a mean CD4 cell count of 291.4 ± 215.9/μl compared to 719.0 ± 156.0/μl for the HIV-infected patients and the HIV-negative controls, respectively (P = 0.001). Fifty-eight HIV-infected patients had CD4 cell count of >200/μl, whereas 42 had CD4 cell count of ≤200/μl. [Table 1] shows the demographic and clinical features of HIV-infected patients and the controls. In the study population, the mean values of LV dimensions were within the normal range. However, HIV-infected patients had significantly higher LV posterior wall thickness in diastole, LV internal diameter in systole, LVMI and RWT compared to the controls. The mean values of indices of LV systolic and diastolic function were also within the normal range in the study population. However, HIV-infected patients had significantly reduced LV EF, LV FS and DT compared to the controls. Details are shown in [Table 2].
|Table 1: Demographic and clinical features of human immunodeficiency virus-infected patients compared to the controls|
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|Table 2: Echocardiography left ventricular dimension and functions in human immunodeficiency virus-infected patients compared to the controls|
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The LV FS and isovolumic relaxation time are significantly reduced in HIV-infected patients with CD4 cell count ≤200/μl compared to those with CD4 cell count >200/μl. However, there was no significant difference in other echocardiographic findings across CD4 subsets, as shown in [Table 3]. Echocardiographic abnormalities were more common in the HIV-infected patients compared with the HIV-negative controls [Table 4]. These include increased RWT, dilated LV, LV hypertrophy, LV systolic and diastolic dysfunctions. The distribution of abnormal LV dimension and functions according to CD4 cell count levels is shown in [Table 5]a and [Table 5]b. The LVIDd and LVMI did not show any significant correlation with CD4 cell count, ([r] = −0.018; P = 0.863 and [r] = 0.012; P = 0.902, respectively.
|Table 3: Echocardiography left ventricular dimension and functions of human immunodeficiency virus-infected patient compared across CD4 subsets|
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|Table 4: Echocardiography prevalence of abnormal left ventricular dimension and functions in human immunodeficiency virus-infected patients compared to controls|
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[Table 6]a and [Table 6]b show the post hoc analyses of the relationship between LV dimension and functions in HIV-positive patients with CD4 cell count ≤200/ul compared to HIV-positive patients with CD4cell count of >200/ul, respectively. As shown in [Figure 1], the LV systolic function showed a significant positive correlation with CD4 cell count, ([r] = 0.384; P = 0.001). This is unlike the LV diastolic function which did not show any significant correlation with CD4 cell count, ([r] = 0.137; P = 0.189).
|Figure 1: Relationship between left ventricular systolic function (ejection fraction%) and CD4 cell count of human immunodeficency virus positive patients|
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| Discussion|| |
The present study suggests that treatment-naïve HIV-infected patients had larger LV mass and more echocardiographic abnormalities compared to their seronegative counterparts. Similar findings have been reported by other workers.,,,, In the present study, 12% of the HIV-infected patients had LV dilatation compared to 6% in the controls. Olusegun-Joseph et al. using the same LVIDd cut off value of 5.2 cm as in the present study, reported 15% prevalence of LV dilatation among treatment-naïve HIV-infected patients and 2% in the HIV-negative controls, respectively. A higher prevalence of LV dilatation was reported by Longo-Mbenza et al. in Congo, using an LVIDd cutoff value of 5.5 cm. In that study, it was noted that 24.4% of patients with HIV infection and 3.5% of the controls had LV dilatation. The fact that LV dilatation was reported to be significantly higher in the advance AIDS group (i.e., patients in the later stage of disease profile) than in the HIV-positive group (early stage of disease profile), could possibly account for the higher prevalence of LV dilatation recorded in that study. A lower prevalence of 2%, for isolated LV cavity dilatation, was reported in a study done in Zimbabwe. The lower prevalence of LV dilatation recorded in that study may be attributed to a higher LVIDd cutoff value of 5.7 cm that was used in that study, compared to the cutoff value of 5.2 cm used in the present study.
Other studies, conducted both locally and internationally, have also reported LV cavity dilatation in treatment-naïve HIV-positive patients. Danbauchi et al. in Zaria, noted that treatment-naïve HIV-infected patients in stage III/IV HIV/AIDS had significantly higher LV cavity diastolic diameter compared to HIV/AIDS patients on antiretroviral drugs at the same stage of the disease. Furthermore, Silva Cardoso et al. in Portugal, noted significantly increased LV diastolic diameters in HIV-positive patients compared with HIV-negative controls. However, LV dilatation was reported to be absent in all the HIV-infected patients and HIV-negative controls in a similar study done in Enugu. Similarly, Okeahialam and Anjorin, in Jos, Nigeria, did not observe any significant difference in the LV cavity dimension of the 33 HIV treatment naïve patients when compared to their 29 seronegative counterparts. This might be because the patients in the study by Okeahialam et al., were at the early stage of the disease.
Nine of the HIV-positive patients had echo evidence of LV hypertrophy, based on the stated criteria. This is similar to the findings of Uwanuruochi et al. at Enugu using the same LVMI criteria. The prevalence is much lower than the study by Longo-Mbenza et al. in Congo, that reported a very high prevalence of LV hypertrophy. The reasons for this disparity are by no means certain. It might be related to the severity of the stage of the disease in the different study groups. The presence of LV hypertrophy in HIV-positive patients could account for the reported a higher prevalence of diastolic dysfunction in HIV-positive patients, compared to their seronegative counterparts.,, Hemodynamic changes in the HIV-positive patients impose a burden on the cardiovascular system which could be partly responsible for the changes in LV dimension.
Thirty-three (33%) of the HIV-infected patients had impaired LV systolic function compared to 8% of the controls in the present study. This is similar to the findings of Olusegun-Joseph et al., who reported a 30% prevalence of LV systolic dysfunction in HIV-infected patients compared to 8% in the control group. Furthermore, studies done in Portugal and Brazil reported the prevalence of LV systolic dysfunction in treatment-naive HIV-infected patients as 32% and 31.5%, respectively., Adebola et al. in their study, reported that only one of the HIV-positive patients had systolic dysfunction. The low prevalence of systolic dysfunction might be partly due to the lower LVEF cutoff of 45% adopted for that study. It should be noted that different LVEF (%) and LVFS (%) cutoff criteria were adopted by different studies on LV systolic function in the past. This might have contributed to the differences in the reported prevalence of systolic dysfunction among HIV-positive patients.
The present study also showed a significant positive correlation between systolic function parameters and CD4 cell count levels in the HIV-positive patients. This is in keeping with the findings of the study done in Brazil which reported that HIV-infected patients with a more advanced infection, i.e., those with CD4 cell count <500/μl, had significantly abnormal LV systolic function when compared with patients with CD4 cell count >500/μl. While the present study reported a higher prevalence of diastolic dysfunction in HIV-positive patients compared to healthy controls, the diastolic function did not show any significant correlation with CD4 cell count of the HIV-positive patients. The study done in Lagos reported that LV systolic and diastolic dysfunctions were more common with HIV-infected patients with very low CD4 cell count compared with patients that had higher CD4 cell count. As stated earlier, cardiac involvement in HIV infection is multifactorial and may arise as a result of myocardial invasion with HIV itself, opportunistic infections, viral infections, autoimmune response to viral infection, HAART-related cardiac toxicity, nutritional, and trace element (selenium) deficiencies.,,,,
The echocardiography machine used in the present study did not have tissue Doppler imaging function, which would have been more helpful in further categorizing diastolic function in the study population.
| Conclusion|| |
Cardiac abnormalities such as increased LV cavity dilatation, LV hypertrophy, LV systolic, and diastolic dysfunction were more common in treatment-naive HIV-infected patients compared with the HIV-negative controls. LV systolic function showed a significant positive correlation with CD4 cell count. However, there was no significant correlation between CD4 cell count and LV dimensions OR between CD4 count and LV diastolic function, in treatment-naïve HIV-infected patients.
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Conflicts for interest
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