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| ORIGINAL ARTICLE |
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| Year : 2019 | Volume
: 5
| Issue : 3 | Page : 197-207 |
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Peripheral arterial disease in antiretroviral therapy naïve HIV infected patients – A single centre case control study from Eastern India
Dibbendhu Khanra1, Anindya Mukherjee2, Arunansu Talukdar3, Anindya Mukherjee4, SK Sinha5
1 Department of Cardiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
2 Department of Cardiology, Nilratan Sicar Medical College and Hospital, Kolkata, West Bengal, India
3 Department of General Medicine, Medical College Hospital, Kolkata, West Bengal, India
4 Department of Community Medicine, Medical College Hospital, Kolkata, West Bengal, India
5 Department of Cardiology, LPS Institution of Cardiology, Kanpur, Uttar Pradesh, India
| Date of Submission | 15-Mar-2019 |
| Date of Decision | 26-Jun-2019 |
| Date of Acceptance | 23-Sep-2019 |
| Date of Web Publication | 20-Dec-2019 |
Correspondence Address:
Dr. Dibbendhu Khanra
Department of Cardiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jpcs.jpcs_13_19
Background and Objectives: Human immunodeficiency virus (HIV)-induced endothelial dysfunction leads to premature atherosclerosis, which may manifest as peripheral arterial disease (PAD) of the lower limbs. Studies are not available on the prevalence of PAD among antiretroviral therapy (ART)-naïve HIV-infected population. The objective was to explore the prevalence of PAD among HIV seropositive cases and to determine the relation of PAD with HIV infectivity and with CD4 count. Materials and Methods: This hospital-based case-control study included 100 newly diagnosed HIV seropositive ART naïve cases (age 20–49 years) and 100 HIV seronegative frequency or group matched controls. Demographic, clinical and routine laboratory parameters, and ankle-brachial pressure index (ABI) were studied. PAD was diagnosed by Doppler study of lower limb arteries. Results: The prevalence of PAD was significantly more among HIV-infected cases (71%) in comparison to HIV-negative controls (P < 0.001). Abnormalities in ABI were present among 75% (53/71) of total PAD cases in our study. Among the cases of PAD, 53% (38/71) patients were asymptomatic. The mean CD4 count among the HIV-positive PAD cases was 220 cells/dl. HIV seropositivity was found to be significantly associated with the development of PAD. Male gender, concurrent tuberculosis, and low CD4 count came out to be individually associated with PAD among HIV seropositive cases in multivariate analysis. Conclusions: The prevalence of symptomatic and asymptomatic PAD was high among ART-naïve HIV-infected cases of relatively younger age group. Future studies should validate the Doppler findings suggestive of PAD among HIV seropositive patients with different inflammatory markers. Prospective studies on Doppler evaluation of endothelial dysfunction among asymptomatic HIV patients should be undertaken to establish or disprove the role of ART.
Keywords: CD4 count, Doppler study, human immunodeficiency virus/acquired immune deficiency syndrome, peripheral artery disease
How to cite this article:
Khanra D, Mukherjee A, Talukdar A, Mukherjee A, Sinha S K. Peripheral arterial disease in antiretroviral therapy naïve HIV infected patients – A single centre case control study from Eastern India. J Pract Cardiovasc Sci 2019;5:197-207 |
How to cite this URL:
Khanra D, Mukherjee A, Talukdar A, Mukherjee A, Sinha S K. Peripheral arterial disease in antiretroviral therapy naïve HIV infected patients – A single centre case control study from Eastern India. J Pract Cardiovasc Sci [serial online] 2019 [cited 2023 Jun 4];5:197-207. Available from: https://www.j-pcs.org/text.asp?2019/5/3/197/273734 |
| Introduction | |  |
Acquired immune deficiency syndrome (AIDS) is one of the most devastating modern epidemics to have affected humankind. 37.9 million people are living with human immunodeficiency virus (HIV) worldwide.[1] India harbors 21.17 lakh (17.11 lakh–26.49 lakh) people with HIV in 2015 which is about 0.26% (0.22%–0.32%) of the total adult population.[2] HIV infection spares not a single system of the human body, and the vascular system is no exception. Decades of clinical research have explored opportunistic infection among people with HIV, their predisposition to malignancies, and adverse effects of antiretroviral therapy (ART), but the knowledge of vascular involvements of HIV infection is still limited. HIV infection causes direct endothelial dysfunction or damage and premature atherosclerosis, which have been established by molecular and radiological markers in a good number of studies.[3]
Peripheral arterial disease (PAD) is largely underdiagnosed in HIV-infected patients. Forty percent of patients of coronary artery disease have associated peripheral vascular disease, 14% have carotid artery stenosis, and 17% have associated renal artery stenosis.[4] PAD is an ice-berg disease where gangrene or intermittent claudication represents merely the 10%–20% of diseased population, but the rest harbor the pathology in minor scale in the form of endothelial dysfunction.[4] Thus, the angiographic demonstration of arterial stenosis has been replaced with the demonstration physiological aberration in the flow dynamics of peripheral arteries. To capture the submerged mass with involved arteries in the subclinical form newer methodologies are devised in the form of duplex ultrasound (DUS), which needs sophisticated machines and trained operators. To screen the disease in a larger scale use of ankle-brachial pressure index (ABI) has been recommended.[5] There are insufficient data on the prevalence of abnormal ABI among the general healthy population and total burden of PAD is still obscure.[6] Furthermore, there is only a handful of data on the prevalence of PAD in South-Asian people.[7]
On the other hand, Doppler ultrasound can precisely confirm as well as localize PAD. Doppler ultrasonography was found to have a sensitivity of 92% and a specificity of 98% in aortoiliac disease. For femoropopliteal disease, these values were calculated to be 88% and 98%, respectively.[8] Doppler study of lower limb arteries can reflect the physiological disturbance in the flow dynamics of the peripheral arteries and alteration of normal waveforms can suggest endothelial dysfunction which is the harbinger of future PAD.[9] Doppler studies can directly visualize the vessel wall and its pathology in the forms of plaque, calcifications, or intimal thickness.[9] Increased carotid intima-media thickness has been recognized as a marker of increased cardiovascular events among people with HIV.[10] Flow-mediated dilation of brachial arteries are also recognized as endothelial dysfunction among people with HIV.[10] There is substantial evidence that endothelial dysfunction among people with HIV correlates with the inflammatory state and abnormal ABI among people with HIV have been observed to correlate with osteoprotegerin, von Willebrand factor and other inflammatory markers.[10] Lower limb arteries being smaller in caliber than carotid arteries and brachial arteries are more prone to develop atherosclerosis and thus are affected earlier and poses a threat to the lower limbs. However, the imaging of the lower limb arteries did not gain much attention because of its technical difficulties and highly operator-based results. Thus, the American College of Cardiology/American Heart Association has approved ABI as a screening tool for the diagnosis of PAD which is reasonably sensitive and specific, but not validated among Indians and often full of inconsistencies when compared to Doppler results.[5],[7],[11]
Communicable diseases associated with HIV or AIDS is being managed aggressively in recent years and new HIV infection is also falling down globally as well as in India.[1],[2] Managing noncommunicable diseases and improving the quality of life among people with HIV stands important in recent HIV medicine. PAD among people with HIV can be attributed to conventional factors such as old age, male sex, obesity, smoking, dyslipidemia, hypertension, and diabetes mellitus as well as other factors like HIV-induced endothelial damage or dysfunction, opportunistic infections which include tuberculosis (TB) and last but not the least ART.[3],[10]
Studies have explored the prevalence of PAD among people with HIV and risk factors contributing to this condition, but no such studies were conducted among ART-naïve people with HIV of younger age group. Our objective was to explore the pattern of distribution of PAD among HIV-infected ART-naïve cases in comparison to the HIV-negative control group, to assess the association of HIV infection in developing PAD and its relation with CD4 count. ABI was measured in both cases and controls and the diagnosis of PAD was made by Doppler assessment of lower limb arteries.
| Materials and Methods | | |
Materials
This case-control study was conducted at the HIV clinic of Medical College and Hospital, Kolkata, one of the largest referral centers of West Bengal and Eastern India and from June 2012 to September 2013. Newly diagnosed HIV seropositive ART-naïve cases, aged between 20 and 49 years, without any established diagnosis of diabetes mellitus, hypertension, dyslipidemia, or PAD were eligible for the study. Initially, 142 newly detected HIV-positive cases were approached, 32 patients did not fulfill the eligibility criteria, and 10 patients did not give consent. Hence, we studied 100 cases of newly diagnosed HIV seropositive ART naïve patients as cases and 100 HIV seronegative persons (attending ear, nose, and throat, ophthalmology and dermatology Outpatient Department) as controls.
Sample size
The current estimate of PAD is 202 million cases worldwide with very substantial numbers in Southeast Asia and about a third of peripheral artery disease cases in these regions were in young people.[4] Around 20–40 million are likely to have intermittent claudication and 100 million atypical leg symptoms.[5] Furthermore, up to 45 million of the 202 million with peripheral artery disease will die from coronary or cerebrovascular disease during 10 years period.[6] There are no standard data on the prevalence of PAD among Indians, but the prevalence of PAD is rising.[6],[12] Prevalence of PAD among the general population (aged 20–49 years) of the middle and lower economic countries range between 10% and 25% and maximum among South Asians.[6] Sample sizes in each group of case and control were 100 with 1:1 ratio between cases and controls being maintained (the Kelsey et al. formula used).
Ethics
This study was approved by the Institutional Ethics Committee of Medical College and Hospital, Kolkata. All participants signed informed consent to participate.
Methods and equipment
Demographic, clinical, and laboratory parameters, including HIV antibody testing, CD4 count, fasting blood sugar, and lipid profile were documented. Edinburgh Claudication Questionnaire was filled for all the cases and controls.[13]
HIV infection was diagnosed by trained counselors of integrated counseling and testing center which is approved by the National AIDS Control Organisation (NACO). The diagnosis of HIV was made on the basis of positive HIV antibody testing (rapid or laboratory-based enzyme immunoassay: Pareekshak Triline). This was confirmed by a second HIV antibody test (rapid or laboratory-based enzyme immunoassay: Pareekshak Trispol) relying on different antigens or of different operating characteristics from. CD4 testing was conducted using Multiset V2.2 FACSCalibur (#E97300192) system (expressed in counts/dl) in NACO accredited ART center.
Diabetes was defined as a fasting blood glucose of >126 mg/dl (>7.0 mmol/L) after 8 h of fasting or postprandial blood glucose >200 mg/dl (>11.1 mmol/L) after 75 g glucose ingestion or patients on oral antidiabetic agents.[14] Dyslipidemia (abnormal lipid profile) was defined as any one of those having serum low-density lipoprotein cholesterol >190 mg/L, high-density lipoprotein cholesterol <40 mg/L levels, and serum triglyceride >200 mg/L or on anti-hyperlipidemic drugs.[15] Hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or on anti-hypertensive medications.[16]
Duplex ultrasound
Duplex ultrasonography, comprising real-time brightness (B-mode/gray scale) imaging and color pulsed-wave provides both anatomical and functional information about the arterial segments under investigation. B-mode imaging permits visual resolution of arterial wall layers and characterization of atherosclerotic plaques by gray-scale imaging. Color Doppler ultrasonography complements the information obtained by B-mode and pulsed-wave Doppler ultrasonography, as it visualizes moving blood and detects turbulence.
DUS study of lower limbs was performed by a single experienced radiologist with PHILIPS iu22 xMATRIX Ultrasound system using 1-3 MHz Broadband linear array transducer and 5–7 MHz curved array transducer with color Doppler and power Doppler assessment. The wall, lumen, and flow of the main arteries from the abdominal aorta to the ankles were evaluated. The percentage of stenosis was estimated by the peak systolic velocity ratio. Plaque was defined as 1.2-mm thickening of the intima-media of the arterial wall, with or without calcifications.
Doppler US had an overall sensitivity of 92% and a specificity of 99% for stenosis using angiography in all lower limb arteries, which were quite comparable to those invasive methods.[9] PAD has been defined on the basis of loss of usual triphasic pattern with abnormal spectrum in continuous Doppler (earliest), or stenosis or plaque in Doppler study of lower limb arteries.
Ankle-brachial pressure index
Patients rested for 5 min lying on a bed, after which blood pressure was measured at the posterior tibialis and dorsalis pedis arteries of both ankles with a 5.0 MHz vascular Nicolet Elite Doppler probe (Viasys) and a sphygmomanometer. Brachial pressure was simultaneously measured at both arms by PRESORID sphygmomanometer with cuff size adapted to the arm circumference. For each leg, the ABI was calculated by dividing the higher systolic ankle pressure by the higher brachial systolic pressure. The ABI threshold of 0.90, measured at rest, has 79% sensitivity and 96% specificity to detect stenoses of >50% reduction in arterial luminal diameter.[5]
Statistical analysis
Data were collected in Microsoft Excel 2007 software, and the relevant bar diagram was prepared using the same software. The univariate, bivariate, and multivariate analysis for different parameters for testing of hypothesis and finding out association were performed using IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY, USA). In bivariate analysis, estimation of risk was done by calculating odds ratio (OR). Pearson's Chi-square test was applied for test of significance. In multivariate analysis as most of the parameters were qualitative so logistic regression model was used to explore adjusted OR.
| Results | | |
There was no significant difference in the distribution of age and gender, residence among HIV-positive cases in comparison to HIV-negative controls. Significantly, low level of literacy, monthly family income was noted among HIV-positive cases. Furthermore, significantly, lower body mass index (BMI) among the HIV-positive cases was found in our study. No significant differences were noted in smoking and alcohol intake among HIV-positive cases and HIV-negative controls. History of claudication was more common among HIV-positive cases in comparison to HIV-negative controls. In risk factor analysis, abnormal glycemic status, and the presence of hypertension were found to have no significant difference among the HIV-negative controls. However, significantly, higher abnormalities of lipid profile were noted among HIV-positive cases in comparison to HIV-negative controls [Table 1]. | Table 1: Comparison of sociodemographic-cultural parameters along with clinical and laboratory findings of peripheral arterial disease among human immunodeficiency virus seropositive cases and seronegative controls (n=200)
Click here to view |
We measured ABI and performed lower limb arterial Doppler study of all the controls (n = 100) for detection of PAD. The prevalence of abnormal ABI was significantly higher (OR [95% confidence interval [CI] = 0.35 [0.2–0.6], P < 0.001) among HIV-infected cases in comparison to HIV-negative controls. On Doppler study, the prevalence of PAD was found to be significantly higher among the HIV-infected cases (OR [95% CI] = 0.11 [0.05–0.2], P < 0.001) than the HIV-negative controls.
On the basis of Doppler studies, 71 cases (n = 100) were found to have abnormalities suggestive of PAD among the HIV infected. All (71/71) of the PAD cases had an abnormal spectral pattern, starting from broadening to the loss of normal triphasic wave in continuous Doppler. Apart from flow abnormality stenosis, plaque, or calcification were present in 2, 13, and 10 cases, respectively, in aortoiliac region; 2, 30, and 13 cases, respectively, in femoropopliteal region; and 4, 32, and 24 cases, respectively, in tibial and dorsalis pedis arteries. Abnormalities in ABI were found in total, of 58 HIV-infected cases, which include 75% (53/71) of PAD cases. ABI was abnormal in HIV-infected PAD (53/71) cases which was significantly higher (OR [95% CI] = 14.1 [4.6–42.5], P < 0.001) than in HIV-infected patients without PAD. History of claudication has been found significantly more among HIV seropositive patients [Table 1]. Among the confirmed cases of PAD, 53% (38/71) patients were asymptomatic and 47% (33/71) PAD patients had a history of claudication (31/71), rest pain (1/71), or ulcer (1/71) or abnormal pulsations. About 44% of PAD cases (by Doppler study) had a history of claudication.
PAD was noted significantly more among the HIV seropositive male patients, but no significant difference could be found in the distribution of age, income, residence, religion, literacy, or serostatus of spouse. However, significantly, high prevalence of unemployment was found among the PAD cases. Smoking was significantly associated with PAD cases among HIV-infected persons, but alcohol intake was found to have no significant correlations with PAD. In our study, all the 100 HIV seropositive cases were infected through sexual route. Worse WHO clinical stages were significantly associated with PAD among the HIV-infected persons. Coinfection with TB at the time of the diagnosis of PAD was significantly higher HIV seropositve PAD cases [Table 2]. Mean CD4 count (standard deviation) among the HIV seropositive cases in our study is 294 (202) cells/dl. The median CD4 count among the HIV seropositive PAD cases were 157 cells/dl (minimum 17 cells/dl–maximum 727 cells/dl), whereas median CD4 count among the HIV seropositive cases without PAD were 505 cells/dl (minimum 168 cells/dl–maximum 677 cells/dl). Seventy-seven percent of HIV seropositive patients (55/71) with PAD were found to have CD4 count <350 cells/dl [Figure 1]. | Table 2: Sociodemographic-cultural and disease parameter comparison among human immunodeficiency virus seropositive patients presenting with odds ratio without peripheral arterial disease (n=100)
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 | Figure 1: Distribution of CD4 count among the human immunodeficiency virus seropositive patients with and without peripheral arterial disease (n = 100).
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Abnormal lipid profile, TB and HIV positivity came out to be significantly associated with PAD in multivariate logistic regression analysis of risk factors among our cases [Table 3]. Low CD4 count (<200 cells/dl), presence of TB, and male sex were found to be individually predisposing to PAD in multivariate logistic regression analysis among the HIV seropositive cases [Table 4]. | Table 3: Bivariate and multivariate analysis of parameters associated with peripheral arterial disease among the total study population (n=200)
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 | Table 4: Bivariate and multivariate analysis of parameters associated with peripheral arterial disease among HIV seropositive cases (n=100)
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Claudication and abnormal spectral patterns were exclusively found among HIV seropositive PAD cases in our study [Table 5]. | Table 5: Comparison of sociodemographic-cultural and disease parameters between HIV seropositive and seronegative PAD cases (n=92)
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| Discussion | | |
In our study, 71% of recently diagnosed HIV-infected ART naïve persons are found to have abnormalities indicative of PAD. Loss of normal tri-phasic pattern of arterial flow (in continuous Doppler) was found in all of them, which is the earliest sign suggestive of peripheral artery disease. In occlusive arterial diseases, flow velocity is increased in the region where the lumen is narrowed. Conversely, vascular resistance is decreased as a result of collateral circulation and vasodilation in the distal part of the obstruction. As the disease progresses, the triphasic flow diminishes to a biphasic flow due to the loss of elastic recoil caused by “hardening” of the arteries. If the disease progresses further, the flow loses its pulsatile nature to a monophasic signal with increased diastolic flow owing to regional vasodilation.[8]
In this study, abnormalities in ABI were present among 53% of total HIV seropositive cases which comprised 71% of PAD cases diagnosed by Doppler abnormalities. There are studies which defined PAD among people with HIV by abnormal ABI values which showed the prevalence of PAD among HIV-infected persons can vary from 4.39% to 36.7%.[17],[18],[19],[20],[21],[22],[23],[24],[25] One Indian prospective study from Chennai reported prevalence of PAD among people with HIV to be 7.69% by the means of ABI.[26] Studies on Doppler findings of lower limbs arteries among HIV-infected ART naïve patients are rare except a French case-control study where Doppler evaluations were conducted among HIV-infected ART-naïve patients and it concluded asymptomatic atherosclerosis seems to be more frequent (36.7%) in HIV-positive patients and is associated to lower HDL cholesterol.[27] All of the other studies defined PAD only on the basis of ABI, whereas in our study, we considered findings of Doppler studies as markers of PAD.
Fifty-three percent of PAD patients remain asymptomatic among the HIV-infected persons which also corroborates with findings of other studies. Hence, Doppler study of HIV patients can greatly aid in the diagnosis of subclinical PAD and thus identify the HIV patients who are at risk of cardiovascular morbidities. There is no head-to-head comparison between ABI and Doppler abnormalities among HIV seropositive patients, but our study points that Doppler study of lower limb arteries can be even better than ABI to diagnose endothelial dysfunction owing to the fact that physiological alteration of flow dynamics appears earlier than alteration of ABI. However, future studies are required to assess sensitivity and specificity of ABI and Doppler to detect PAD among HIV seropostive patients.
High level of unemployment was observed among HIV seropositive PAD patients in our study which indicates their poor quality of life. Overall, level of employment was found to be significantly low among the HIV seropositive cases which is corroborating with literature.[2] Higher level of dyslipidemia was found among HIV seropositive cases which is also observed in other Indian studies.[28] Lower level of BMI was found to be an significantly associated with PAD in our study probably due to overall low level of BMI among HIV seropositive cases which corroborates with other studies and goes against the conventional notion of BMI >25 (i.e., obesity) as a risk factor for PAD.[29]
The prevalence of PAD (71%) in our study, in younger HIV-infected cases without ART is alarmingly high and some ethnic factor might be responsible. Lower level of mean CD4 count (224 cells/dl) and worse WHO clinical stages noted among the HIV associated PAD cases. However, TB and other opportunistic infections, in the setting of HIV induced immune-suppression, can confound the high prevalence of PAD.[30] HIV-induced endothelial dysfunction with or without vascular inflammation might be contributing to such high prevalence of PAD. However, in the present study, we did not validate the results by looking at inflammatory markers (interleukins, C-reactive proteins, cellular adhesion molecules, etc.,) associated with PAD which is a limitation of our study.
Seventy-seven percent of HIV seropositive cases with PAD had CD4 count <350 cells/dl and were indicated for ART as per the NACO guideline.[2] Abnormalities in Doppler were observed when the patients were newly diagnosed and were ART naïve. HIV itself is known to predispose endothelial inflammation as well dysfunction leading to subclinical PAD and ART might be beneficial in curbing down the inflammatory state and reversing the Doppler abnormalities. However, no such prospective studies are available to explore the role of ART in reverting PAD among people with HIV. The study design is also limited to establishing a causal relationship of HIV infection and PAD. Moreover, protease inhibitors are notorious for premature atherosclerosis, but the first-line ART (as per the NACO guideline) does only contain reverse transcriptase inhibitors and their role in causing or reversing atherosclerosis are unsettled. Prospective studies with large population would be necessary to explore these controversial but salient issues.[2],[10]
Fifty-five percent of HIV seropostive patients with PAD were found to have CD4 count <200 cells/dl in our study. Low CD4 count has been found to be an independent contributing factor for the development of PAD among people with HIV in our study. However, we did not analyze the HIV viral load in parallel to CD4 count which is a limitation of our study. Apart from low CD4 count male sex and co-infection with TB have been associated with PAD among the HIV-infected persons corroborating the fi ndings of other studies. Co-infection with TB is also found to be significantly associated to PAD among HIV seropostive cases in our study, even after adjusting other conventional risk factors and is a novel finding in our study. In PAODH study, traditional risk factors such as diabetes mellitus, tobacco use including smoking, hypertension, and dyslipidemia were not found to be independent risk factors similar to our study results.[26] Duration of HIV infection, overall duration of HIV treatment and CD4 count <300 were associated with a higher rate of PAD, but these did not attain statistical significance in multivariate analysis as risk factors in PAODH study, but duration of protease inhibitor was significantly contributing to PAD among HIV seropositive cases.[26]
In a large prospective study involving 91,953 participants over a median follow-up of 9 years, infection with HIV was found to be associated with a 19% increased risk of PAD beyond that explained by traditional atherosclerotic risk factors.[31] In an European study by Andreas et al., prevalence of PAD was found to be higher among people with HIV compared to uninfected controls, even after adjusting for traditional risk factors.[32] In an African study, the prevalence of PAD was 6.9% and 60% of patients with PAD were symptomatic.[33] However, in a study from Thailand, the prevalence of abnormal ABI (<1.00) was significantly lower in the HIV-infected group than the uninfected control group, whereas that of PAD (ABI ≤0.90) was not significantly different between the two groups.[34] The prevalence of PAD among people with HIV, found in various studies is depicted in [Table 6]. | Table 6: Prevalence of peripheral arterial disease among human immunodeficiency virus-infected patients in various studies
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Hence, Doppler abnormalities suggestive of endothelial dysfunction are alarmingly high among people with HIV and can outnumber ABI-defined cases of PAD. HIV seropositivity is an independent risk factor for the development of PAD among the younger people living with HIV. That may serve as an indirect evidence of HIV-mediated endothelial dysfunction leading to premature atherosclerosis as a part of “inflammaging” of HIV-mediated direct vascular damage.[35] Low CD4 count, low WHO clinical stage, and coinfection with TB have been found to be significantly associated with PAD among the HIV seropositive patients. Doppler identification and localization of PAD can be undertaken among the HIV patients with low CD4 count, low WHO clinical stage, and coinfection with TB even when patients are asymptomatic.
Being a case-control study, causal association of HIV and PAD could not be assessed. Duration or actual severity of HIV infection could not be assessed among the cases as HIV viral load assay could not be performed. Seventy-one percent prevalence of PAD among ART naive HIV seropositive patients is high as compared to existing literature. Berkesonion bias can also be responsible. We did not validate Doppler results suggestive of PAD among PLHIV cases with different inflammatory markers associated with PAD. We could not perform angiography either which is the gold standard test for PAD. We could not perform endovascular biopsy to rule out vascular inflammation either.
To conclude, the prevalence of symptomatic and asymptomatic PAD was high among ART-naïve HIV-infected cases of relatively younger age group. Future studies should validate the Doppler findings suggestive of PAD among HIV seropositive patients with different inflammatory markers. Prospective studies on Doppler evaluation of endothelial dysfunction among asymptomatic HIV patients should be undertaken to establish or disprove the role of ART.
Ethics clearance
Ethical clearance was obtained from Institutional Ethics Committee of Medical College and Hospital, Kolkata on date 28/12/2011.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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