Epidemiology of selected cardiovascular disease risk factors in people living with HIV compared to HIV-uninfected adults in northwestern Tanzania and southern Uganda
Bazil Baltazar Kavishe
Epidemiology of selected cardiovascular disease risk factors in people living with HIV compared to HIV-uninfected adults in northwestern Tanzania and southern Uganda - Mwanza, Tanzania: Catholic University of Health and Allied Sciences and the University of Copenhagen : 2023 - 217 Pages Includes References
Abstract:
Background: Cardiovascular diseases (CVD) are increasing rapidly in sub-Saharan Africa (SSA) at a time when infectious diseases such as HIV remain common. CVD are projected to surpass infectious diseases as the leading cause of early mortality in SSA by the year 2030. The sharp rise in CVD in the region is partly explained by the rising prevalence of traditional risk factors and demographic transition. The epidemiology of CVD risk factors including dyslipidemia, chronic kidney disease, high blood pressure (BP) and low heart rate variability (HRV) is poorly described in SSA. In particular, little is known about the overlap between these CVD risk factors and HIV infection.
Objectives: The main objective of the study was to describe the epidemiology of selected CVD risk factors in people living with HIV (PLWH) compared to HIV-uninfected adults enrolled from similar East African communities. Study specific objectives were: 1) To describe the distribution of lipid abnormalities and cardiovascular risk scores in PLWH and HIV-uninfected adults in the general population in northwestern Tanzania and Southern Uganda, 2) To determine prevalence of impaired renal function and its associated factors among PLWH compared to HIVuninfected adults in northwestern Tanzania, 3) To determine factors associated with changes in BP in PLWH during the first year of antiretroviral therapy (ART) initiation compared to HIV-uninfected adults in northwestern Tanzania, and 4) To determine factors associated with nocturnal HRV in PLWH during the first year of ART compared to HIV-uninfected adults in northwestern Tanzania.
Methods: Four sub-studies (studies 1 - 4) were conducted each addressing one of the stated objectives. For the first study (objective 1), I conducted secondary analysis of data collected as part of population-based survey for chronic diseases among adults in northwestern Tanzania and southern Uganda. Data on demographics, lifestyle risk factors for non-communicable diseases (NCDs), anthropometry, BP, HIV status, blood glucose and blood lipids were available for analysis. Lipid profile was described by HIV status. Factors associated with blood lipid levels were determined using multivariable linear regression. Framingham 10-year cardiovascular risk scores were calculated with and without lipids. The findings were published in PLoS One journal under the title, “Dyslipidemia and cardiovascular risk scores in rural and urban populations in northwestern Tanzania and Southern Uganda”.
For the second study (objective 2) I conducted cross-sectional secondary data analysis of participants’ enrolment data for a larger cohort study on diabetes and associated complications in northwestern Tanzania also known as Co-infections And Co-morbidities Associated with Diabetes in Africa (CICADA). Analysed data to address this objective included demographic characteristics, lifestyle risk factors for NCDs, anthropometry, fat mass, fat-free mass, haemoglobin level, blood glucose, HIV status and CD4+ T-cell count. I used multivariable linear regression to determine factors associated with both eGFR as a continuous outcome (primary analysis) and impaired renal function defined by eGFR < 60 mL/min/1.73 m2 (secondary analysis). Study findings were published in BMC Nephrology journal under the title, “Risk factors for impaired renal function in HIV-infected and HIV-uninfected adults: a cross-sectional study in northwestern Tanzania”.
The third study (objective 3), was a one-year prospective cohort sub-study of ART-naïve PLWH and HIVuninfected adults enrolled in CICADA study. BP and body composition data were collected at baseline and 12 months follow-up. I used multivariable linear regression to compare BP changes in PLWH and in HIV-uninfected adults, and assessed the relationship between changes in body composition with changes in BP. Findings from this study have been published in the American Journal of Hypertension under the title, “Blood pressure and body composition during first year of antiretroviral therapy in people with HIV compared to HIV-uninfected community controls”. The fourth study (objective 4) was a one-year prospective cohort study, involving a sub-set of ART-naïve PLWH and HIV-uninfected participants enrolled in study 3. At enrolment, data on demographic characteristics, alcohol consumption, smoking and anthropometry were collected, and tested blood samples for hemoglobin, glucose, insulin, CD4+ T-cell count and C-reactive protein. Nocturnal HRV and heart rate were measured at baseline and first year follow-up. Mixed effect linear regression was used to determine predictors of lower HRV. The findings from study 4 under the title “Changes in nocturnal heart rate variability in people living with HIV during the first year of antiretroviral therapy compared to HIV-uninfected community controls” have been published in the Journal of AIDS.
Results: Study 1 involved 1043 participants in Tanzania and 914 in Uganda who had lipids data. Overall, 187 participants were HIV-infected. PLWH had significantly higher mean levels of atherogenic blood lipids compared to HIVuninfected. Overall, one-third of adults in the study population had dyslipidemia. Low high-density lipoprotein cholesterol (HDL-C) affected 32-45% of rural adults. High total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B were found in <15% of adult population but were more common in urban adults. Factors independently associated with higher mean LDL-C and apolipoprotein B were female gender, older age, higher education, higher income, obesity, and hypertension. HIV was associated with lower mean LDL-C, and lower mean HDL-C and apolipoprotein A. Framingham cardiovascular risk scores with and without lipids yielded similar results and 90% of study subjects in were classified as “low risk”. Among older adults (>55 years), 30% were classified as “high” or “very high” risk. A total of 655 HIV-uninfected, 956 ART-naïve PLWH and 336 PLWH on ART were enrolled in study 2. The mean age was 41 years (standard deviation = 2) and majority (59%) were females. Overall, the mean estimated Glomerular Filtration Rate (eGFR) was 113.6 mL/min/1.73 m2: 111.2 mL/min/1.73 m2 in HIV-uninfected, 109.7 mL/min/1.73 m2 in ART-naïve PLWH and 129.5 in ART-experienced PLWH. The respective prevalence of impaired renal function was 7.0%: 5.7%, 8.1% and 6.3%. Correlates of lower eGFR were increasing age, higher socioeconomic status, unhealthy alcohol consumption, higher body mass index and diabetes mellitus. Anemia was associated with a >2-fold greater odds of impaired renal function (95% Confidence Interval (CI):1.2 to 3.6, p=0.007) in ART-naïve PLWH but not in other groups (p value for interaction = 0.02). ART naïve PLWH with CD4+ T-cell count <200 cells/μL had 2.7 (95% CI: 1.4, 5.0) higher odds of impaired renal function compared to ≥350 cells/μ CD4+ T-cell count group. For study 3, longitudinal BP data was available for 640 PLWH and 299 HIV-uninfected adults. Sixty-four percent were women and the mean age was 38 years. In PLWH, systolic BP (SBP) increased (114 to 118 mmHg) whereas SBP decreased (125 to 123 mmHg) in HIV-uninfected participants. Fat mass increased by 1.6 kilogram on average in PLWH and was strongly associated with change in BP (p<0.001). The greater increase in SBP in PLWH was partly explained by the lower baseline SBP in this group, but PLWH still experienced a 2.2 (95% CI: 0.3 to 4.2) greater increase in SBP after adjustment. Weight gain partially mediated the relationship between HIV and SBP increase in PLWH; a one-kilogram increase in fat mass accounted for 0.8 mmHg (95% CI: 0.6 to 1.1) increase in SBP. Out of 111 participants enrolled in study 4 (74 PLWH and 37 HIV-uninfected) majority were females and the median age was 40 years. The nocturnal heart rate in PLWH was 4.5 beats per minute higher in PLWH (95% CI: 1.3 to 7.8), p=0.006) compared to HIV-uninfected. In the fully adjusted model (with age, sex, nocturnal heart rate and diabetes), nocturnal HRV was also significantly and persistently lower after one year of ART in PLWH compared to HIV-uninfected adults. PLWH had a 13% lower mean HRV (-10.5, 95% CI: -20.0 to -1.0, p=0.03) than HIV-uninfected. Unlike with nocturnal heart rate, nocturnal HRV did not decrease after one year of ART in PLWH or HIV-uninfected (fully adjusted change = -2.5, 95% CI: -8.9, 3.9, p=0.45). Lower educational attainment, lesser pancreatic -cell function and anemia were associated with higher HRV.
Conclusion: CVD risk factors are common in adults in northwestern Tanzania and southern Uganda and the distribution of these risk factors differs by HIV status. Low HDL-C was the most commonly observed dyslipidemia–affecting nearly one-third of rural populations – and is particularly common in PLWH who have not yet started ART. Impaired renal function is highly prevalent in ART- naïve PLWH. Weight gain, and particularly increased fat mass, contributes to the rapid increase in BP observed in PLWH during the first year of ART. Nocturnal parasympathetic nervous system activity - as quantified by nocturnal HRV – was abnormally low in PLWH compared to HIV-infected adults and persisted even after one year of ART.
Recommendations: Higher levels of atherogenic dyslipidemia in PLWH warrants public health interventions targeted to this group. Interventions for prevention of impaired renal function are needed in the study population with special focus in HIV-infected adults. Studies assessing change in BP over time in PLWH should adjust for change in fat mass or weight. In the meantime, nocturnal heart rate might serve as an easily quantifiable biomarker of nocturnal cardiovascular health in PLWH.
Wurzburg Road 35, BMC Premises, Post Code: 33102: P. O. Box 1464, Mwanza – Tanzania: Phone: +255 28 298 3384: Fax: +255 28 298 3386: Email: vc@bugando.ac.tz: www.bugando.ac.tz
Epidemiology of selected cardiovascular disease risk factors in people living with HIV compared to HIV-uninfected adults in northwestern Tanzania and southern Uganda - Mwanza, Tanzania: Catholic University of Health and Allied Sciences and the University of Copenhagen : 2023 - 217 Pages Includes References
Abstract:
Background: Cardiovascular diseases (CVD) are increasing rapidly in sub-Saharan Africa (SSA) at a time when infectious diseases such as HIV remain common. CVD are projected to surpass infectious diseases as the leading cause of early mortality in SSA by the year 2030. The sharp rise in CVD in the region is partly explained by the rising prevalence of traditional risk factors and demographic transition. The epidemiology of CVD risk factors including dyslipidemia, chronic kidney disease, high blood pressure (BP) and low heart rate variability (HRV) is poorly described in SSA. In particular, little is known about the overlap between these CVD risk factors and HIV infection.
Objectives: The main objective of the study was to describe the epidemiology of selected CVD risk factors in people living with HIV (PLWH) compared to HIV-uninfected adults enrolled from similar East African communities. Study specific objectives were: 1) To describe the distribution of lipid abnormalities and cardiovascular risk scores in PLWH and HIV-uninfected adults in the general population in northwestern Tanzania and Southern Uganda, 2) To determine prevalence of impaired renal function and its associated factors among PLWH compared to HIVuninfected adults in northwestern Tanzania, 3) To determine factors associated with changes in BP in PLWH during the first year of antiretroviral therapy (ART) initiation compared to HIV-uninfected adults in northwestern Tanzania, and 4) To determine factors associated with nocturnal HRV in PLWH during the first year of ART compared to HIV-uninfected adults in northwestern Tanzania.
Methods: Four sub-studies (studies 1 - 4) were conducted each addressing one of the stated objectives. For the first study (objective 1), I conducted secondary analysis of data collected as part of population-based survey for chronic diseases among adults in northwestern Tanzania and southern Uganda. Data on demographics, lifestyle risk factors for non-communicable diseases (NCDs), anthropometry, BP, HIV status, blood glucose and blood lipids were available for analysis. Lipid profile was described by HIV status. Factors associated with blood lipid levels were determined using multivariable linear regression. Framingham 10-year cardiovascular risk scores were calculated with and without lipids. The findings were published in PLoS One journal under the title, “Dyslipidemia and cardiovascular risk scores in rural and urban populations in northwestern Tanzania and Southern Uganda”.
For the second study (objective 2) I conducted cross-sectional secondary data analysis of participants’ enrolment data for a larger cohort study on diabetes and associated complications in northwestern Tanzania also known as Co-infections And Co-morbidities Associated with Diabetes in Africa (CICADA). Analysed data to address this objective included demographic characteristics, lifestyle risk factors for NCDs, anthropometry, fat mass, fat-free mass, haemoglobin level, blood glucose, HIV status and CD4+ T-cell count. I used multivariable linear regression to determine factors associated with both eGFR as a continuous outcome (primary analysis) and impaired renal function defined by eGFR < 60 mL/min/1.73 m2 (secondary analysis). Study findings were published in BMC Nephrology journal under the title, “Risk factors for impaired renal function in HIV-infected and HIV-uninfected adults: a cross-sectional study in northwestern Tanzania”.
The third study (objective 3), was a one-year prospective cohort sub-study of ART-naïve PLWH and HIVuninfected adults enrolled in CICADA study. BP and body composition data were collected at baseline and 12 months follow-up. I used multivariable linear regression to compare BP changes in PLWH and in HIV-uninfected adults, and assessed the relationship between changes in body composition with changes in BP. Findings from this study have been published in the American Journal of Hypertension under the title, “Blood pressure and body composition during first year of antiretroviral therapy in people with HIV compared to HIV-uninfected community controls”. The fourth study (objective 4) was a one-year prospective cohort study, involving a sub-set of ART-naïve PLWH and HIV-uninfected participants enrolled in study 3. At enrolment, data on demographic characteristics, alcohol consumption, smoking and anthropometry were collected, and tested blood samples for hemoglobin, glucose, insulin, CD4+ T-cell count and C-reactive protein. Nocturnal HRV and heart rate were measured at baseline and first year follow-up. Mixed effect linear regression was used to determine predictors of lower HRV. The findings from study 4 under the title “Changes in nocturnal heart rate variability in people living with HIV during the first year of antiretroviral therapy compared to HIV-uninfected community controls” have been published in the Journal of AIDS.
Results: Study 1 involved 1043 participants in Tanzania and 914 in Uganda who had lipids data. Overall, 187 participants were HIV-infected. PLWH had significantly higher mean levels of atherogenic blood lipids compared to HIVuninfected. Overall, one-third of adults in the study population had dyslipidemia. Low high-density lipoprotein cholesterol (HDL-C) affected 32-45% of rural adults. High total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B were found in <15% of adult population but were more common in urban adults. Factors independently associated with higher mean LDL-C and apolipoprotein B were female gender, older age, higher education, higher income, obesity, and hypertension. HIV was associated with lower mean LDL-C, and lower mean HDL-C and apolipoprotein A. Framingham cardiovascular risk scores with and without lipids yielded similar results and 90% of study subjects in were classified as “low risk”. Among older adults (>55 years), 30% were classified as “high” or “very high” risk. A total of 655 HIV-uninfected, 956 ART-naïve PLWH and 336 PLWH on ART were enrolled in study 2. The mean age was 41 years (standard deviation = 2) and majority (59%) were females. Overall, the mean estimated Glomerular Filtration Rate (eGFR) was 113.6 mL/min/1.73 m2: 111.2 mL/min/1.73 m2 in HIV-uninfected, 109.7 mL/min/1.73 m2 in ART-naïve PLWH and 129.5 in ART-experienced PLWH. The respective prevalence of impaired renal function was 7.0%: 5.7%, 8.1% and 6.3%. Correlates of lower eGFR were increasing age, higher socioeconomic status, unhealthy alcohol consumption, higher body mass index and diabetes mellitus. Anemia was associated with a >2-fold greater odds of impaired renal function (95% Confidence Interval (CI):1.2 to 3.6, p=0.007) in ART-naïve PLWH but not in other groups (p value for interaction = 0.02). ART naïve PLWH with CD4+ T-cell count <200 cells/μL had 2.7 (95% CI: 1.4, 5.0) higher odds of impaired renal function compared to ≥350 cells/μ CD4+ T-cell count group. For study 3, longitudinal BP data was available for 640 PLWH and 299 HIV-uninfected adults. Sixty-four percent were women and the mean age was 38 years. In PLWH, systolic BP (SBP) increased (114 to 118 mmHg) whereas SBP decreased (125 to 123 mmHg) in HIV-uninfected participants. Fat mass increased by 1.6 kilogram on average in PLWH and was strongly associated with change in BP (p<0.001). The greater increase in SBP in PLWH was partly explained by the lower baseline SBP in this group, but PLWH still experienced a 2.2 (95% CI: 0.3 to 4.2) greater increase in SBP after adjustment. Weight gain partially mediated the relationship between HIV and SBP increase in PLWH; a one-kilogram increase in fat mass accounted for 0.8 mmHg (95% CI: 0.6 to 1.1) increase in SBP. Out of 111 participants enrolled in study 4 (74 PLWH and 37 HIV-uninfected) majority were females and the median age was 40 years. The nocturnal heart rate in PLWH was 4.5 beats per minute higher in PLWH (95% CI: 1.3 to 7.8), p=0.006) compared to HIV-uninfected. In the fully adjusted model (with age, sex, nocturnal heart rate and diabetes), nocturnal HRV was also significantly and persistently lower after one year of ART in PLWH compared to HIV-uninfected adults. PLWH had a 13% lower mean HRV (-10.5, 95% CI: -20.0 to -1.0, p=0.03) than HIV-uninfected. Unlike with nocturnal heart rate, nocturnal HRV did not decrease after one year of ART in PLWH or HIV-uninfected (fully adjusted change = -2.5, 95% CI: -8.9, 3.9, p=0.45). Lower educational attainment, lesser pancreatic -cell function and anemia were associated with higher HRV.
Conclusion: CVD risk factors are common in adults in northwestern Tanzania and southern Uganda and the distribution of these risk factors differs by HIV status. Low HDL-C was the most commonly observed dyslipidemia–affecting nearly one-third of rural populations – and is particularly common in PLWH who have not yet started ART. Impaired renal function is highly prevalent in ART- naïve PLWH. Weight gain, and particularly increased fat mass, contributes to the rapid increase in BP observed in PLWH during the first year of ART. Nocturnal parasympathetic nervous system activity - as quantified by nocturnal HRV – was abnormally low in PLWH compared to HIV-infected adults and persisted even after one year of ART.
Recommendations: Higher levels of atherogenic dyslipidemia in PLWH warrants public health interventions targeted to this group. Interventions for prevention of impaired renal function are needed in the study population with special focus in HIV-infected adults. Studies assessing change in BP over time in PLWH should adjust for change in fat mass or weight. In the meantime, nocturnal heart rate might serve as an easily quantifiable biomarker of nocturnal cardiovascular health in PLWH.
Wurzburg Road 35, BMC Premises, Post Code: 33102: P. O. Box 1464, Mwanza – Tanzania: Phone: +255 28 298 3384: Fax: +255 28 298 3386: Email: vc@bugando.ac.tz: www.bugando.ac.tz