HIV Reports
Increased Prevalence of Elevated Blood Pressures in HIV-Infected Children, Adolescents and Young Adults Sam Chatterton-Kirchmeier, MD,* Andres F. Camacho-Gonzalez, MSc, MD,†‡ Courtney E. McCracken, PhD,§ Rana Chakraborty, MD, PhD,†‡ and Donald L. Batisky, MD¶ Background: HIV-infected children and young adults have cardiovascular disease risk factors reflecting chronic infection and the effects of combination antiretroviral (ARV) therapy. We thus sought to characterize the prevalence of and risk factors for high blood pressure (HBP) in this population. Methods: Retrospective chart review classified subjects aged 2–25 years based on a single clinic blood pressure (BP) reading as normal BP, pre-HBP or HBP. Variables suspected to contribute to elevated BP were compared including body mass index, tobacco use, medical comorbidities, ARV or other medication use, dyslipidemia, ethnicity and family history. Results: In all, 47 of 266 subjects (18%) were found to have HBP. Among children and adolescents aged 2–17 years, 21 of 107 (20%) had HBP. Comorbidities believed to elevate BP, such as polycystic ovarian syndrome, obstructive sleep apnea or cocaine exposure, were significant risk factors for elevated BP, with 35% of subjects with these comorbidities having HBP, compared with 16% of subjects without (P = 0.01). Male gender and tobacco use were also risk factors associated with elevated BPs. HBP was more common in overweight subjects (26%) than not overweight (15%) but did not reach statistical significance (P = 0.15). ARV medication use and higher HIV-1 RNA were not associated with HBP. Conclusions: Our finding of 20% prevalence of HBP in a cohort of HIVinfected children represents a potentially alarming figure. The explanation for this finding is unclear, but even if it is because of comorbid conditions, the life-long cardiovascular risks associated with HIV infection and its management mandate the need for closer monitoring and possibly treatment of elevated BP in this population. Key Words: HIV, children, adolescents, blood pressure, hypertension (Pediatr Infect Dis J 2015;34:610–614)
W
orldwide 3.4 million children under age 15 years are HIV infected.1 The introduction of combination antiretroviral therapy (cART) has substantially modified the course of HIV disease progression by lengthening survival in those receiving access to care, transforming HIV from an almost uniformly fatal illness into a chronic infection.2 However, with increasing life spans, the long-term complications of HIV infection and antiretroviral (ARV) therapy are becoming more apparent, with increased cardiovascular disease (CVD) risk of particular concern.
Hypertension (HTN) is a well-characterized risk factor for CVD in adults, with approximately 50% of coronary heart disease and 75% of stroke in developed countries attributable to elevated blood pressure (BP), as well as predisposing to atherosclerosis, renal failure and other adverse outcomes.3,4 HIV infection is also associated with a significant risk of CVD, manifested by abnormal lipid profiles, arterial inflammation, premature atherosclerosis and elevated systemic inflammatory markers.5,6 Chronic cART administration adds to the CVD risk with associated metabolic derangements including lipodystrophy and impaired glucose tolerance, as well as a linear increase in cardiovascular-related death for up to 5 years of ARV exposure.7,8 In a study of HIV-infected adults by Jung et al,9 HTN was associated with a much higher frequency of persistent proteinuria, coronary heart disease and myocardial infarction compared with nonhypertensive, HIV-infected subjects. The prevalence of HTN in HIV-infected adults has been described as ranging from 8% to 34%.10 The prevalence of HTN in the HIV-negative adult population in the U.S., by comparison, is 29%.11 Less is known about the CVD risks faced by children and adolescents with HIV, although recent studies have identified several potential risk factors. These include significant lipid abnormalities in children receiving cART and increased carotid intimamedia thickness, suggesting the process of atherosclerosis begins at an early age.12 Given that these patients may encounter potential cardiotoxic therapies throughout life and that the evidence for BP tracking from childhood to adulthood is strong, it is important to characterize additional, and possibly treatable, CVD risk factors.13 The goal of this retrospective study was a preliminary description of the prevalence of elevated BP in our cohort of HIV-infected children, adolescents and young adults, as well as to identify risk factors for the occurrence of elevated BP. To our knowledge, no previous studies have focused on BP in HIV-infected children. Anecdotal observations in our clinic suggested that we would encounter an increased prevalence of elevated BP compared with the HIV-uninfected pediatric population. Our intent was to perform a more rigorous investigation if compelling findings emerged, to help direct early detection of high BP (HBP), identify patients at high risk for developing CVD or renal disease and guide management as necessary.
MATERIALS AND METHODS Study Population
Accepted for publication March 5, 2015. From the *Emory University School of Medicine, Atlanta, GA; †Pediatric Infectious Diseases, Emory University, Atlanta, GA; ‡Ponce Family and Youth Clinic at the Grady Infectious Diseases Program, Atlanta, GA; §Department of Pediatrics, Emory University School of Medicine, Atlanta, GA; and ¶Division of Pediatric Nephrology, Emory University, Atlanta, GA. The two senior authors (R.C. and D.L.B.) equally contributed to this manuscript. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Sam Chatterton-Kirchmeier, MD, 747 52nd St, Oakland, CA 94609. E-mail: [email protected] Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0891-3668/15/3406-0610 DOI: 10.1097/INF.0000000000000695
610 | www.pidj.com
We conducted a retrospective chart review of patients currently enrolled at the Ponce Family and Youth Clinic in the Grady Infectious Diseases Program. This is the primary pediatric and adolescent HIV clinic for the state of Georgia, which follows patients from birth to age 25 years. Inclusion criteria consisted of a confirmed diagnosis of HIV/AIDS and a BP reading at a recent clinic visit. Patients with documented renovascular HTN were excluded. The research protocol was approved by Emory University Institutional Review Board and Grady Healthcare Research Oversight Committee.
Blood Pressure Measurement and Definition The clinic used Dinamap Pro automatic oscillometric monitors with appropriate sized cuffs (GE Medical Systems Inc.,
The Pediatric Infectious Disease Journal • Volume 34, Number 6, June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
The Pediatric Infectious Disease Journal • Volume 34, Number 6, June 2015
Milwaukee, WI), and BP measurements were taken at regular clinic visits. A single BP measurement at the most recent clinic visit from the start of the study period was used, excluding sick visits. BP values in patients under age 18 years were classified according to guidelines from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents based on gender, age and height.14 However, as we deviated from the rigorous Fourth Report HTN definition by using a single BP measurement instead of the recommended multiple measurements on separate occasions, we employed different but analogous terminology: HBP and pre-HBP in place of HTN and pre-HTN, respectively. BP categories were defined as normal BP [systolic BP (SBP) or diastolic BP (DBP) 400 vs. ≤ 400 copies/mL) and dyslipidemia (yes/no). Because of small cell counts and missing data, exact P values were reported for some comparisons when the asymptotic distribution was not appropriate. Preliminary multivariable analysis of risk factors was conducted but not included because effective sample size became exceedingly small (data not shown).
RESULTS Study Population Characteristics Two hundred and sixty-six subjects met study criteria and were included for analysis, representing 95% of the 279 HIV-positive patients enrolled at the clinic at the time of study commencement. Thirteen patients were excluded because of insufficient data. Demographic and clinical characteristics of all study subjects are summarized in Table, Supplemental Digital Content 1, http://links.lww. com/INF/C91. Mean age of study participants was 17.8 years (SD 4.8 years). The great majority of subjects were AA (89.9%) with a male predominance (57.1%). Most subjects were taking or had received ARVs in the previous 2-year period (80.7%), but virologic control and immune status were widely variable; 64.7% achieved virologic control of ≤400 copies/mL and 42.1% had a CD4 count of ≥500 cells/mm3. Most study participants were infected perinatally (58.3%); horizontally infected individuals represented 33.8% of the cohort; 24.6% of patients used tobacco, and 29.7% of patients had BMI defined as overweight. There were 43 subjects with a PMH associated with increased BP, with the following number of subjects for each condition: obesity, 11; HTN, 10; cocaine exposure, 7; history of HBP, 5; very preterm birth, 3; HIV-associated nephropathy, 3; type 1 diabetes, 3; Polycystic Ovarian syndrome, 2; IgA nephropathy, 2; end stage renal disease, 2; sleep apnea, 1; amphetamine exposure, 1. Seven subjects had two of the listed diagnoses.
Study Population Age Stratification There were notable differences in characteristics between the children/adolescents (N = 107; mean age, 13.0; SD, 3.7 years) and young adult (N = 159; mean age, 21.0; SD, 1.8 years) age groups (see Table, Supplemental Digital Content 1, http://links.lww.com/ INF/C91). In the latter group, there was a significantly greater proportion of males and individuals with horizontally acquired infection. The 74.8% of the children/adolescent subjects were infected perinatally compared with 47.2% of young adults. The younger group had better overall HIV disease control with lower rates of detectable HIV-1 RNA and higher rates of CD4 T-Cell counts ≥500 cells/mm3. Hundred percent of the children/adolescents received ARVs, compared with only 67.5% of the young adults. Significantly more young adults had tobacco exposure.
Prevalence of HBP by Age Groups Of the 266 HIV-infected subjects in the cohort, 17.7% were categorized as HBP and 34.6% pre-HBP (Table 1). The 19.6% of the children/adolescent group exhibited BPs categorized as HBP compared with 16.3% of young adults. The young adult group had a much greater prevalence of pre-HBP (47.8%) compared with the children/adolescent group (15.0%). Systolic factors contributed to elevated BP more than diastolic, especially in the pediatric group, with 15.9% of this group exhibiting systolic HBP, compared with only 6.5% exhibiting diastolic HBP. www.pidj.com | 611
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
The Pediatric Infectious Disease Journal • Volume 34, Number 6, June 2015
Chatterton-Kirchmeier et al
TABLE 1. Prevalence of HBP of Entire Cohort and by Age Group
Systolic or Diastolic Systolic Diastolic
BP Status
All Subjects 2–25 years (N = 266)
Children and Adolescents 2–17 years (N = 107)
Young Adults 18–25 years (N = 159)
Normal BP Pre-HBP HBP Normal BP Pre-HBP HBP Normal BP Pre-HBP HBP
127 (47.7%) 92 (34.6%) 47 (17.7%) 149 (56.0%) 86 (32.3%) 31 (11.7%) 199 (74.8%) 47 (17.7%) 20 (7.5%)
70 (65.4%) 16 (15.0%) 21 (19.6%) 83 (77.6%) 7 (6.5%) 17 (15.9%) 88 (82.2%) 12 (11.2%) 7 (6.5%)
57 (35.8%) 76 (47.8%) 26 (16.3%) 66 (41.5%) 79 (49.7%) 14 (8.8%) 111 (69.8%) 35 (22.0%) 13 (8.2%)
P
Increased Prevalence of Elevated Blood Pressures in HIV-Infected Children, Adolescents and Young Adults Sam Chatterton-Kirchmeier, MD,* Andres F. Camacho-Gonzalez, MSc, MD,†‡ Courtney E. McCracken, PhD,§ Rana Chakraborty, MD, PhD,†‡ and Donald L. Batisky, MD¶ Background: HIV-infected children and young adults have cardiovascular disease risk factors reflecting chronic infection and the effects of combination antiretroviral (ARV) therapy. We thus sought to characterize the prevalence of and risk factors for high blood pressure (HBP) in this population. Methods: Retrospective chart review classified subjects aged 2–25 years based on a single clinic blood pressure (BP) reading as normal BP, pre-HBP or HBP. Variables suspected to contribute to elevated BP were compared including body mass index, tobacco use, medical comorbidities, ARV or other medication use, dyslipidemia, ethnicity and family history. Results: In all, 47 of 266 subjects (18%) were found to have HBP. Among children and adolescents aged 2–17 years, 21 of 107 (20%) had HBP. Comorbidities believed to elevate BP, such as polycystic ovarian syndrome, obstructive sleep apnea or cocaine exposure, were significant risk factors for elevated BP, with 35% of subjects with these comorbidities having HBP, compared with 16% of subjects without (P = 0.01). Male gender and tobacco use were also risk factors associated with elevated BPs. HBP was more common in overweight subjects (26%) than not overweight (15%) but did not reach statistical significance (P = 0.15). ARV medication use and higher HIV-1 RNA were not associated with HBP. Conclusions: Our finding of 20% prevalence of HBP in a cohort of HIVinfected children represents a potentially alarming figure. The explanation for this finding is unclear, but even if it is because of comorbid conditions, the life-long cardiovascular risks associated with HIV infection and its management mandate the need for closer monitoring and possibly treatment of elevated BP in this population. Key Words: HIV, children, adolescents, blood pressure, hypertension (Pediatr Infect Dis J 2015;34:610–614)
W
orldwide 3.4 million children under age 15 years are HIV infected.1 The introduction of combination antiretroviral therapy (cART) has substantially modified the course of HIV disease progression by lengthening survival in those receiving access to care, transforming HIV from an almost uniformly fatal illness into a chronic infection.2 However, with increasing life spans, the long-term complications of HIV infection and antiretroviral (ARV) therapy are becoming more apparent, with increased cardiovascular disease (CVD) risk of particular concern.
Hypertension (HTN) is a well-characterized risk factor for CVD in adults, with approximately 50% of coronary heart disease and 75% of stroke in developed countries attributable to elevated blood pressure (BP), as well as predisposing to atherosclerosis, renal failure and other adverse outcomes.3,4 HIV infection is also associated with a significant risk of CVD, manifested by abnormal lipid profiles, arterial inflammation, premature atherosclerosis and elevated systemic inflammatory markers.5,6 Chronic cART administration adds to the CVD risk with associated metabolic derangements including lipodystrophy and impaired glucose tolerance, as well as a linear increase in cardiovascular-related death for up to 5 years of ARV exposure.7,8 In a study of HIV-infected adults by Jung et al,9 HTN was associated with a much higher frequency of persistent proteinuria, coronary heart disease and myocardial infarction compared with nonhypertensive, HIV-infected subjects. The prevalence of HTN in HIV-infected adults has been described as ranging from 8% to 34%.10 The prevalence of HTN in the HIV-negative adult population in the U.S., by comparison, is 29%.11 Less is known about the CVD risks faced by children and adolescents with HIV, although recent studies have identified several potential risk factors. These include significant lipid abnormalities in children receiving cART and increased carotid intimamedia thickness, suggesting the process of atherosclerosis begins at an early age.12 Given that these patients may encounter potential cardiotoxic therapies throughout life and that the evidence for BP tracking from childhood to adulthood is strong, it is important to characterize additional, and possibly treatable, CVD risk factors.13 The goal of this retrospective study was a preliminary description of the prevalence of elevated BP in our cohort of HIV-infected children, adolescents and young adults, as well as to identify risk factors for the occurrence of elevated BP. To our knowledge, no previous studies have focused on BP in HIV-infected children. Anecdotal observations in our clinic suggested that we would encounter an increased prevalence of elevated BP compared with the HIV-uninfected pediatric population. Our intent was to perform a more rigorous investigation if compelling findings emerged, to help direct early detection of high BP (HBP), identify patients at high risk for developing CVD or renal disease and guide management as necessary.
MATERIALS AND METHODS Study Population
Accepted for publication March 5, 2015. From the *Emory University School of Medicine, Atlanta, GA; †Pediatric Infectious Diseases, Emory University, Atlanta, GA; ‡Ponce Family and Youth Clinic at the Grady Infectious Diseases Program, Atlanta, GA; §Department of Pediatrics, Emory University School of Medicine, Atlanta, GA; and ¶Division of Pediatric Nephrology, Emory University, Atlanta, GA. The two senior authors (R.C. and D.L.B.) equally contributed to this manuscript. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Sam Chatterton-Kirchmeier, MD, 747 52nd St, Oakland, CA 94609. E-mail: [email protected] Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0891-3668/15/3406-0610 DOI: 10.1097/INF.0000000000000695
610 | www.pidj.com
We conducted a retrospective chart review of patients currently enrolled at the Ponce Family and Youth Clinic in the Grady Infectious Diseases Program. This is the primary pediatric and adolescent HIV clinic for the state of Georgia, which follows patients from birth to age 25 years. Inclusion criteria consisted of a confirmed diagnosis of HIV/AIDS and a BP reading at a recent clinic visit. Patients with documented renovascular HTN were excluded. The research protocol was approved by Emory University Institutional Review Board and Grady Healthcare Research Oversight Committee.
Blood Pressure Measurement and Definition The clinic used Dinamap Pro automatic oscillometric monitors with appropriate sized cuffs (GE Medical Systems Inc.,
The Pediatric Infectious Disease Journal • Volume 34, Number 6, June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
The Pediatric Infectious Disease Journal • Volume 34, Number 6, June 2015
Milwaukee, WI), and BP measurements were taken at regular clinic visits. A single BP measurement at the most recent clinic visit from the start of the study period was used, excluding sick visits. BP values in patients under age 18 years were classified according to guidelines from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents based on gender, age and height.14 However, as we deviated from the rigorous Fourth Report HTN definition by using a single BP measurement instead of the recommended multiple measurements on separate occasions, we employed different but analogous terminology: HBP and pre-HBP in place of HTN and pre-HTN, respectively. BP categories were defined as normal BP [systolic BP (SBP) or diastolic BP (DBP) 400 vs. ≤ 400 copies/mL) and dyslipidemia (yes/no). Because of small cell counts and missing data, exact P values were reported for some comparisons when the asymptotic distribution was not appropriate. Preliminary multivariable analysis of risk factors was conducted but not included because effective sample size became exceedingly small (data not shown).
RESULTS Study Population Characteristics Two hundred and sixty-six subjects met study criteria and were included for analysis, representing 95% of the 279 HIV-positive patients enrolled at the clinic at the time of study commencement. Thirteen patients were excluded because of insufficient data. Demographic and clinical characteristics of all study subjects are summarized in Table, Supplemental Digital Content 1, http://links.lww. com/INF/C91. Mean age of study participants was 17.8 years (SD 4.8 years). The great majority of subjects were AA (89.9%) with a male predominance (57.1%). Most subjects were taking or had received ARVs in the previous 2-year period (80.7%), but virologic control and immune status were widely variable; 64.7% achieved virologic control of ≤400 copies/mL and 42.1% had a CD4 count of ≥500 cells/mm3. Most study participants were infected perinatally (58.3%); horizontally infected individuals represented 33.8% of the cohort; 24.6% of patients used tobacco, and 29.7% of patients had BMI defined as overweight. There were 43 subjects with a PMH associated with increased BP, with the following number of subjects for each condition: obesity, 11; HTN, 10; cocaine exposure, 7; history of HBP, 5; very preterm birth, 3; HIV-associated nephropathy, 3; type 1 diabetes, 3; Polycystic Ovarian syndrome, 2; IgA nephropathy, 2; end stage renal disease, 2; sleep apnea, 1; amphetamine exposure, 1. Seven subjects had two of the listed diagnoses.
Study Population Age Stratification There were notable differences in characteristics between the children/adolescents (N = 107; mean age, 13.0; SD, 3.7 years) and young adult (N = 159; mean age, 21.0; SD, 1.8 years) age groups (see Table, Supplemental Digital Content 1, http://links.lww.com/ INF/C91). In the latter group, there was a significantly greater proportion of males and individuals with horizontally acquired infection. The 74.8% of the children/adolescent subjects were infected perinatally compared with 47.2% of young adults. The younger group had better overall HIV disease control with lower rates of detectable HIV-1 RNA and higher rates of CD4 T-Cell counts ≥500 cells/mm3. Hundred percent of the children/adolescents received ARVs, compared with only 67.5% of the young adults. Significantly more young adults had tobacco exposure.
Prevalence of HBP by Age Groups Of the 266 HIV-infected subjects in the cohort, 17.7% were categorized as HBP and 34.6% pre-HBP (Table 1). The 19.6% of the children/adolescent group exhibited BPs categorized as HBP compared with 16.3% of young adults. The young adult group had a much greater prevalence of pre-HBP (47.8%) compared with the children/adolescent group (15.0%). Systolic factors contributed to elevated BP more than diastolic, especially in the pediatric group, with 15.9% of this group exhibiting systolic HBP, compared with only 6.5% exhibiting diastolic HBP. www.pidj.com | 611
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
The Pediatric Infectious Disease Journal • Volume 34, Number 6, June 2015
Chatterton-Kirchmeier et al
TABLE 1. Prevalence of HBP of Entire Cohort and by Age Group
Systolic or Diastolic Systolic Diastolic
BP Status
All Subjects 2–25 years (N = 266)
Children and Adolescents 2–17 years (N = 107)
Young Adults 18–25 years (N = 159)
Normal BP Pre-HBP HBP Normal BP Pre-HBP HBP Normal BP Pre-HBP HBP
127 (47.7%) 92 (34.6%) 47 (17.7%) 149 (56.0%) 86 (32.3%) 31 (11.7%) 199 (74.8%) 47 (17.7%) 20 (7.5%)
70 (65.4%) 16 (15.0%) 21 (19.6%) 83 (77.6%) 7 (6.5%) 17 (15.9%) 88 (82.2%) 12 (11.2%) 7 (6.5%)
57 (35.8%) 76 (47.8%) 26 (16.3%) 66 (41.5%) 79 (49.7%) 14 (8.8%) 111 (69.8%) 35 (22.0%) 13 (8.2%)
P
