The prevalence of hypertension in people living with HIV at Senkatana ART Clinic, Maseru, Lesotho.

doi:10.21203/rs.3.rs-5122880/v1

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The prevalence of hypertension in people living with HIV at Senkatana ART Clinic, Maseru, Lesotho.

https://doi.org/10.21203/rs.3.rs-5122880/v1

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Background

Hypertension is a modifiable risk factor for Cardiovascular and Chronic Kidney disease among other complications[1]. Hypertension (HTN) and cardiovascular diseases (CVD) have emerged among people living with HIV (PLHIV) as the most important prevalent contributors of non-AIDS related mortality [2, 3]. Unfortunately, limited data is available regarding the prevalence of hypertension and of risk factors associated with HTN among PLHIV in Lesotho. In this study we aim to determine the prevalence of HTN and identify risk factors associated with HTN in PLHIV in Maseru, Lesotho.

Method

A cross-sectional study was conducted from February to July 2022 at Senkatana ART clinic, Maseru, Lesotho. Participants randomly selected from among PLHIV who attended the clinic were aged 18 years and above, were on HAART for at least 12 months and provided consent. Structured questionnaires were used to collect data on the socio-demographic, medical, family and behavioral history. Height, Weight and blood pressure (BP) were measured and Body mass index (BMI) calculated. HTN was defined as a systolic BP of ≥ 140 mmHg and/or diastolic BP of ≥ 90 mmHg or a self-reported use of antihypertensive medication(s). Data analysis was done using excel and SAS statistical software (v9.4). Bivariable and multivariable analyses identified risk factors associated with HTN.

Results

300 patients participated in the study, of which 64% were females and 36% male. The mean age was 51 years. The prevalence of hypertension was 57% (exact 95% CI: 51.2%, 62.7%). Of those with HTN, 33.3% were newly diagnosed during this study (exact 95% CI: 26.3%, 40.9%). 69% of participants previously diagnosed with HTN had uncontrolled HTN at enrollment (exact 95% CI: 60.0%, 77.6%). Age and BMI were independent risk factors for HTN in this sample.

Conclusion

According to this study, HTN is prevalent and poorly controlled in PLHIV attending Senkatana ART Clinic and 33 percent of those with HTN were newly diagnosed. Introduction of routine hypertension prevention, diagnostic and treatment measures have the potential to reduce morbidity and mortality within this population. This study provides a model for future investigation of the prevalence and management of other non-communicable diseases (NCDs) to determine optimal clinical practice guidelines for Lesotho. It also shows that siloed single disease oriented care misses critical co-morbidities and therefore brings evidence to support a model of comprehensive healthcare delivery.

General Practice

Hypertension

PLHIV

There is a growing burden of NCDs among PLHIV, particularly in resource limited health systems of the sub-Saharan Africa which also bear high burdens of HIV prevalence [11]. Hypertension (HTN) is a major modifiable risk factor for ischemic heart disease, ischemic stroke, intracerebral hemorrhage, heart failure, chronic kidney disease (CKD), and end stage renal disease [1]. HTN and cardiovascular diseases (CVD) have emerged as among the most important and prevalent contributors of non-AIDS related mortality [2, 3].

Hypertension is responsible for nearly 13–14% of all global mortality and 7–10% of global disability-adjusted life years [2, 3]. Approximately 1 in 4 adults in the world have HTN and Africa as a World Health Organization (WHO) region has the highest burden of disease among adults, with some studies estimating 46% of the African population over 25 years of age to be hypertensive and with a steady or increasing overall trend. [4]

Globally, 35% of all HIV-infected adults on highly active antiretroviral therapy (HAART) have hypertension [8]. The estimated prevalence of hypertension in adults over 50 years of age on HAART rises to 42.0% globally, 45.9% in low- and middle-income countries [2, 12, 13, 14]. The prevalence of HTN in PLHIV in Eastern and Southern Africa it is estimated to be 19.9% [13]. In Western Cape province, South Africa (SA), the crude prevalence of hypertension in PLHIV was 41.2% [17]. This poses a serious problem because HTN is an important predictor of long-term survival in PLHIV[7].

It has been found that PLHIV who have HTN at the time of their diagnosis have more than twice the hazard of early mortality than those without HTN which worsens if HTN is undiagnosed hence untreated. Furthermore, PLHIV on HAART are at an increased risk (two times higher) of acquiring HTN than HIV-uninfected counterparts and even at higher risk of HTN-related complications. Undiagnosed HTN further increases the risk of HTN related complications [6, 7].

PLHIV are at higher risk of HTN due to low CD4 count, high viral burden, exposure to HAART, longer duration of the HIV infection. This may be explained by chronic inflammation over time, exposure to certain HAART regimens which raise the risk of HTN and long-term immunosuppression. PLHIV also present with the general risk factors known to all other sectors of the community outside HIV like older age, smoking, high BMI and positive family history of HTN among others [7, 8, 13].

Globally, it is estimated that there are about 37.9 million people living with HIV (PLHIV) and more than 70% of them reside in Sub-Saharan Africa [17]. Approximately 22.7% of the Lesotho population, a Southern African LMIC, aged 15 years of age and above is living with HIV according to the Lesotho Population-Based HIV Impact Assessment 2020 [5]. The HTN prevalence in the general population in Lesotho was estimated to be 22% in adults in 2015 [ 9]. However, the prevalence of HTN among PLHIV and the common risk factors for this population in Lesotho is unknown. Therefore, this study aims to determine the prevalence of HTN in PLHIV and identify the risk factors associated with HTN in PLHIV attending Senkatana ART Clinic, Maseru, Lesotho.

a. Study design, setting and population:

A cross-sectional study was conducted from February to July 2022 at Senkatana ART clinic, Maseru, Lesotho.

Study site

Senkatana ART clinic is found in Maseru, the capital district of Lesotho. Lesotho is a landlocked country by Republic of South Africa. Lesotho has a total population of 2 135 000, whereby 25% of this reside in Maseru district. Senkatana ART Clinic primarily serves a total population of 23120 from 9 villages in Maseru. All are HIV positive adults receiving HAART from this center. It also serves as a national referral center for special HIV and TB cases. It provides HIV services comprising of prevention, counselling, diagnosis, treatment and monitoring. It follows the test and treat criteria regardless of CD4 cell count.

Population

Participants randomly selected from among PLHIV who attended the clinic were aged 18 years and above, were on HAART for at least 12 months and provided informed consent. Excluded from the study were pregnant patients due to the complexity of hypertensive disease in pregnancy and all those unwilling to provide consent or severely ill.

b. Sample Size Determination:

We determined, using SAS PROC POWER, that a sample of 300, drawn from a total clinic population of 23,120, would ensure with a probability of at least 0.8 that the 95% confidence interval the study estimates for the prevalence of HTN would have a half width no larger than 0.05. The calculation assumes that the true prevalence of HTN in the clinic population is in accord with the published estimate of 0.22 [9].

c. Sampling and Data Collection:

During patients’ follow-up visits to the clinic, study participants were selected randomly using the lottery method from their attendance list. They were then invited to participate in the study and provide informed consent. Structured questionnaires were used to collect data on the socio-demographic, behavioral, medical and family history. Clinical data (duration of HIV Infection, HAART regimen etc.) was collected both from the patient and from clinical records. Anthropometric data (weight in kg, height in meters, BP) was measured during the interview and BMI calculated (kg/m2).

Systolic and diastolic blood pressure (BP) were measured in the left arm three times at an interval of at least five minutes using an electronic blood pressure monitor, with the patient remaining in a sitting position for at least 15min before the first measurement. The average of the two measurements was recorded in mmHg.

d. Definitions:

In this study, HTN was defined as self-reported use of antihypertensive medication and/or elevated systolic blood pressure of ≥ 140mmHg and/or diastolic blood pressure of ≥ 90mmHg. Participants were categorized as smokers if they smoked at least one cigarette per week in the last 12 months, and as alcohol consumers if they consumed any alcoholic drink at least seven times in a week in the last 12 months. BMI was classified as underweight (BMI < 18.5kg/m2), normal (BMI 18.5-24.9kg/m2), overweight (25-29.9kg/m2) and obese (BMI ≥ 30kg/m2). Family history for HTN was considered positive for individuals with first degree relatives who are known with HTN. WHO clinical staging I, II, III, IV of the participants was taken from their clinic file/ records. Staging is as referenced [18]

e. Plan of Analysis:

Data was analyzed using SAS statistical software (v9.4) and Microsoft excel. HTN prevalence was calculated as the number of those qualifying as having HTN divided by the total number sampled. The percentage of undiagnosed HTN was calculated as the number of those newly diagnosed during the study divided by the total number of those qualifying as having HTN.

Categorical risk factors were summarized in terms of counts (frequencies and percentages/ proportions). Continuous risk factors were summarized in terms of means and standard deviations. To identify potential risk factors for HTN, those with and without HTN were compared, in bivariable analyses, using Chi-square tests or Fisher's exact tests (for categorical factors) and t-tests (for continuous factors). Multivariable logistic regression models were used to assess potential confounding in the bivariable comparisons. A P-value of <0.05 was considered for statistical significance.

f. Ethical considerations:

Approval to conduct the study was obtained from the Research Coordinating Unit. Ministry of Health Lesotho as well as from the hospital management to proceed with the study. Before participation in the study, the purpose of the study; IRB safeguards and informed consent were shared with each study participant. The information that was obtained from participants was the minimum necessary to conduct the study, and any interventions and interactions occurred in private settings. The confidentiality of the data was protected by assigning a unique study number for each study participant. Data collection questionnaires were translated to Sesotho for the participants who do not understand English.

4.1. Demographic characteristics of the Study Participants:

Demographic characteristics are presented in Table 1. A total of 300 participants were included in study analysis, of which 63.7% were females. The mean age was 51.6 years old and 55.7% of the participants aged 50 years and above. 87 (29.0%) participants had a positive family history of HTN (first degree relative), majority 162 (54%) were married, and about half 161 (53.7%) had not attended school beyond grade 8. Only 48 (16.0%) of the participants were smokers and 62 (20.7%) consumed alcohol.

4.2 Clinical characteristics:

The mean BMI was 28.1kg/m2, and the majority 64.6% were overweight/obese. Most of the participants were on WHO clinical stage 1. All were on HAART, and the most frequently used regimen (76%) was TDF/3TC/DTG. 57.3% had HIV infection duration of more than 10 years and 57% at similar duration on HAART. Table 2.

There was a statistically significant difference in HTN prevalence between people aged above 50 years and those below (p from Fisher's exact test < 0.0001) with a higher prevalence among those aged 50 years and above (73.1%). The overweight and obese group, BMI ≥ 25.0 kg/m2, was observed to have a higher prevalence of HTN at 63.9% (p from Fisher's exact test = 0.0015) as compared to the normal and underweight group with a HTN prevalence of 44.3%. There was a statistically significant difference among the four marital status groups (p from Chi-square test 0.0009) with the widowed and divorced participants having higher HTN prevalence, 73.9% and 60.9%, respectively. There was no significant difference in HTN prevalence observed in other variables analyzed. Table 4.

4.3 Prevalence of hypertension:

The prevalence of HTN was found to be 57% (171/300) (95% CI: 51.2%, 62.7%). Of the 171 participants with HTN, 57 (33.3%) were newly diagnosed during this study (exact 95% CI: 26.3%, 40.9%). Of the 114 participants who were already on HTN treatment, 79 (69.3%) had uncontrolled HTN (exact 95% CI: 60.0%, 77.6%).

Table 3.

Table 1

**Demographic characteristics of study participants**
Variables	Category	Frequency (%)
Sex	Female	191 (63.7)
	Male	109 (36.3)
Age	Mean	51.6 years
	20–49 years	133 (44.3)
	≥ 50 years	167 (55.7)
Smoking status	Yes	48 (16.0)
	No	252 (84.0)
Alcohol use	Yes	62 (21.4)
	No	228 (78.6)
Family history of HTN	Yes	87 (29.0)
	No	213 (71.0)
Marital status	Single	27 (9.0)
	Married	162 (54.0)
	Widowed	88 (29.3)
	Divorced	23 (7.7)
Educational status	Grade 1–8	161 (53.7)
	Grade 9–12	121 (40.3)
	College and above	18 (6.0)

*In the section of alcohol users, all the first 10 responses received were NO, due to misunderstanding of the questionnaire and therefore were discarded and the total participants for this section reduced to 290.

Table 2

**Clinical characteristics of study participants**
Variables	Categories	Frequency
BMI	Mean (SD)	28.1 kg/m2
	<25.0 kg/m2	106 (35.3%)
	≥ 25.0 kg/m2	194 (64.7%)
Duration of HIV infection	<5 years	19 (6.3%)
	5–10 years	109 (36.3%)
	>10 years	172 (57.3%)
Duration on HAART	<5 years	20 (6.7%)
	5–10 years	109 (36.3%)
	>10 years	171 (57%)
HAART regimen	TDF/3TC/DTG	228 (76%)
	ABC/3TC/DTG	37 (12.3%)
	AZT/3TC/DTG	14 (4.7%)
	AZT/3TC/LPV/r	7 (2.3%)
	ABC/3TC/LPV/r	8 (2.7%)
	TDF/3TC/LPV/r	5 (1.7%)
	TDF/3TC/ATV/r	1 (0.3%)
WHO clinical stage	1	101 (34%)
	2	55 (18%)
	3	133 (44%)
	4	11 (4%)

Table 3

**Prevalence of HTN**
Prevalence of HTN	171/300 (57%)	(95% CI: 51.2%, 62.7%).
Newly diagnosed HTN	57/171 (33%)
Uncontrolled HTN	79/114 (69%)

4.3 Risk Factors associated with HTN in PLHIV

In the multivariable analyses, married participants were, on average, older than those who were single, and those who were divorced were not older than those who were married. Widowed participants were older than those in other marital groups. Therefore, at a given age (in years), HTN is not associated with marital status (p = 0.1370). The prevalence of HTN is highest in the group who receive ABC/3TC/DTG. However, this group is the oldest in terms of mean age. The crude prevalence of HTN is non significantly higher in women than in men (P = 0.0907). However, women are, on average, slightly younger than men. A multivariable model that adjusted for sex, age and BMI status found that older age and high BMI (≥ 25.0 kg/m2) are independent risk factors for HTN in this population, but sex is not.

Table 4

**Bivariable and multivariable analyses of risk factors for HTN**
Variables	Hypertension		P-value Bivariable analysis	P-value, in Multivariable model that adjusts for age (in years) and BMI status
	Yes (N = 171), n (%)	No (N = 129) n (%)
Sex:			0.0907	0.3418
Female	116 (60.7)	75 (39.3)
Male	55 (50.5)	54 (49.5)
Age:			< .0001*	--------
20–49 years	49 (36.8)	84 (63.2)
≥ 50 years	122 (73.1)	45 (26.9)
Smoking status:			0.2032	0.5644
Yes	23 (47.9)	25 (52.1)
No	148 (58.7)	104 (41.3)
Alcohol use:			0.2495	0.9923
Yes	31 (50)	31 (50)
No	140 (58.8)	98 (41.2)
Family history of HTN:			0.7974	0.6393
Yes	51 (58.6)	36 (41.4)
No	120 (56.3)	93 (43.7)
Marital status:			0.0009*	0.3550
Single	11 (40.7)	16 (59.3)
Married	81 (50)	81 (50)
Widowed	65 (73.9)	23 (26.1)
Divorced	14 (60.9)	9 (39.1)
Educational status:			0.1035	0.7294
Grade 1–8	93 (60.3)	64 (39.8)
Grade 9–12	61 (50.4)	60 (49.6)
College and above	13 (72.2)	5 (27.8)
BMI:			0.0015*	------
<25.0 kg/m2	47 (44.3)	59 (55.7)
≥ 25.0 kg/m2	124 (63.9)	70 (36.1)
Duration of HIV infection:			0.2401	0.8334
<5 years	9 (47.4)	10 (52.6)
5–10 years	57 (52.3)	52 (47.7)
>10 years	105 (61)	67 (39)
Duration on HAART:			0.3008	0.7966
<5 years	10 (50)	10 (50)
5–10 years	57 (52.3)	52 (47.7)
>10 years	104 (60.8)	67 (39.2)
HAART regimen:			0.0588	0.0561 (adjusted for BMI) 0.5977 (adjusted for age)
TDF/3TC/DTG	125 (54.8)	103 (45.2)
ABC/3TC/DTG	29 (78.4)	8 (21.6)
AZT/3TC/DTG	7 (50)	7 (50)
AZT/3TC/LPV/r	2 (28.6)	5 (71.4)
ABC/3TC/LPV/r	5 (62.5)	3 (37.5)
TDF/3TC/LPV/r	3 (60)	2 (40)
TDF/3TC/ATV/r	0 (0)	1 (100)
WHO clinical stage:			0.2119	0.3365
1	60 (59.4)	41 (40.6)
2	37 (67.3)	18 (32.7)
3	68 (51.1)	65 (48.9)
4	6 (54.5)	5 (45.5)

The aim of this study was to determine the prevalence of HTN in PLHIV attending Senkatana ART clinic, Maseru, Lesotho and the risk factors associated with HTN in this population. The prevalence of hypertension was found to be 57% (95% CI: 51.2%, 62.7%) of which 33% (exact 95% CI: 26.3%, 40.9%) were newly diagnosed during the study. This prevalence is higher than the global data that reports 35% of PLHIV on HAART having HTN. [8] It is also higher than that reported for the general population of Lesotho (22%) [9] and for other low- and middle-income countries (45.9%) among adults over 50 years of age on HAART [14]. It is higher than 41.2% reported in Western Cape, South Africa, and 23.7% in Malawi [16, 17].

These differences could be attributed to variations in the demographic and metabolic related factors like body mass index and age distribution among the study participants. The mean age of the study participants was 43.0 and 38.4 years in Malawi and Western Cape respectively, while in this study the mean age was 51.6 years. The percentage of overweight participants was 43.9% in Western Cape while in this study it was higher at 63.9%. The difference in HTN prevalences reported could also be because of differences in the study design and definition of hypertension as in Malawi the participants came back for two follow up visits to measure BP while in Western Cape, they were selected form 62 different health facilities among other differences. However, prevalence of hypertension is significant and is a serious issue for Lesotho.

Among participants previously on antihypertensive medication, more than half (69%) had uncontrolled HTN. This may point towards missed opportunities to adequately manage HTN in patients who are regularly in contact with the healthcare system. The percentage of newly diagnosed patients (33%) also points to the need to offer more comprehensive healthcare inclusive of blood pressure screening, monitoring and treatment.

There was no significant association found between the prevalence of hypertension and HIV related factors being the duration of HIV infection, duration of HAART use, HAART regimen and HIV WHO clinical staging in this study. This is contrary to findings in other studies that suggest a significant association between HTN and factors like duration of HIV infection and of HAART exposure. These studies found significant association between duration of HAART exposure and HTN as well as between duration of HIV infection and rise in BP. This could be because of endothelial dysfunction due to chronic inflammation, platelet activation and hypercoagulability caused by direct infection with HIV [17, 20]. Certain side effects of HAART may also put PLHIV at risk for HTN like nephrotoxicity and changes in body constitution [17, 20]. More research with larger sample size, sample including patients from various facilities to explore these association is probably needed for Lesotho.

The prevalence of HTN is highest in the group who receive ABC/3TC/DTG. However, this group is the oldest in terms of mean age so the apparent increase in risk of HTN for this group is explained by their older mean age.

In bivariable analysis there was a significant difference in prevalence of HTN among marital status groups (p value 0.0009). This could be due to age differences as the single participants group had a lower prevalence of HTN, but they were also the youngest in age hence in multivariable analysis there was no association found between marital status and HTN whether adjusted for age (p = 0.1370) or adjusted for both age and BMI (p = 0.3553).

HTN was significantly associated with other risk factors like older age and higher BMI. Age and BMI are independent risk factors for HTN and is in agreement with other African studies [8, 17, 20]. This suggests that the same risk factors affecting the general population also affect PLHIV and therefore there is need to offer a more comprehensive approach to health care in this population by addressing other modifiable risk factors such as maintaining normal weight.

These findings show that comorbidities such as HTN are probably contributing to non-AIDS mortalities among this population as HTN is a well-known risk factor for other NCDs such as CVD and CKD [1, 2, 3]. Early detection and management are critical for prevention of associated complications and this study shows not only the need for early diagnosis of missed cases but addressing poor control among those with a known diagnosis.

Generalizability to the greater population of PLHIV may be limited because Senkatana ART Clinic also attends to PLHIV referred from other centers, even though such complicated referred cases are a minority of the general clinic attendants.

People living with HIV are not exempted from non-communicable diseases and their complications. Hypertension is highly prevalent among PLHIV and a significant percentage of such patients is either undiagnosed or uncontrolled on anti-HTN medication. There is need for patient-oriented approach with holistic, comprehensive and integrated medical care rather than siloed disease-oriented care to address the complexities of PLHIV as in this setting a significant proportion was not diagnosed with associated HTN or properly managed.

Older age and high BMI were found to be independently associated with HTN. Therefore, addressing other modifiable risk factors is crucial. Introduction of routine HTN prevention, diagnostic and treatment measures have the potential to reduce morbidity and mortality within this population and improve the quality of life of patients.

This study demonstrates an intersection between HIV and HTN. It can be expected that this applies to other NCDs, hence this study provides a model for future investigation of the prevalence and management of other NCDs as well as their association to HTN, to determine optimal clinical practice guidelines for Lesotho.

Acknowledgments:

Lesotho Boston Health Alliance FMSTP Faculty supervisors. The Ministry of health Lesotho. Senkatana management and clinical staff. Dr. Chelsea Mcguire, Boston University (USA). Dr. Brian Jack, Boston University (USA).

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The authors declare no competing interests.

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The prevalence of hypertension in people living with HIV at Senkatana ART Clinic, Maseru, Lesotho.

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Abstract

Background

Method

Results

Conclusion

Introduction

Methods

Results

4.1. Demographic characteristics of the Study Participants:

4.2 Clinical characteristics:

4.3 Prevalence of hypertension:

4.3 Risk Factors associated with HTN in PLHIV

Discussion

Limitation of the study

Conclusions and recommendations

Declarations

Acknowledgments:

References

Additional Declarations

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