Print version ISSN 0066-782X
Arq. Bras. Cardiol. vol.95 no.5 São Paulo Oct. 2010 Epub Oct 15, 2010
Evanizio Roque de Arruda JúniorI; Heloisa Ramos LacerdaII,III; Líbia Cristina Rocha Vilela MouraII; Maria de Fátima Pessoa Militão de AlbuquerqueII,IV; Demócrito de Barros Miranda FilhoII; George Tadeu Nunes DinizIV; Valéria Maria Gonçalves de AlbuquerqueIII; Josefina Cláudia Zirpoli AmaralII; Verônica Soares MonteiroIII; Ricardo Alencar de Arraes XimenesII,III
IUniversidade Federal da Paraíba, João Pessoa - PB
IIUniversidade Federal de Pernambuco
IIIUniversidade de Pernambuco
IVInstituto Aggeu Magalhães - FIOCRUZ, Recife, PE - Brazil
BACKGROUND: Hypertension (HBP) is modifiable risk factor, whose control may reduce cardiovascular disease in patients with human immunodeficiency virus (HIV).
OBJECTIVE: To estimate the prevalence of hypertension and describe the characteristics of patients with hypertension infected by HIV/AIDS.
METHODS: A cross-sectional study aligned to a cohort of patients with HIV/AIDS. The study considered hypertension at levels > 140/90 mmHg or use of antihypertensive drugs and pre-hypertension at levels > 120/80 mmHg.
RESULTS: Out of 958 patients, 388 (40.5%) were normotensive, 325 (33.9%) were pre-hypertensive, and 245 (25.6%) were hypertensive. Out of these 245 patients, 172 (70.2%) were aware of the fact there they were hypertensive, and 36 (14.8%) had blood pressure controlled. Sixty-two (62) patients (54.4%) were diagnosed with hypertension after HIV diagnosis. Lipodystrophy occurred in 95 (46.1%) patients; overweight/obesity in 129 (52.7%). Use of antiretrovirals occurred in 184 (85.9%), 89 (41.6%) with protease inhibitors (PI) and 95 (44.4%) without PI. Out of these patients, 74.7 used antivirals > 24 months. Age, family history of hypertension, waist circumference, body mass index and triglyceride levels were higher among hypertensive patients. Time of HIV infection, CD4 count, viral load, time and type of antiretroviral regimen were similar in hypertensive and prehypertensive patients.
CONCLUSION: The high frequency of uncontrolled hypertensive patients and cardiovascular risks in HIV-infected patients point out to the need for preventive and therapeutic measures against hypertension in this group. (Arq Bras Cardiol. 2010; [online].ahead print, PP.0-0)
Key words: Hypertension/prevention & control; acquired immunodeficiency syndrome (AIDS); HIV: life style; risk factors; antihypertensive agents.
While there has been a significant increase in the survival rate of patients with HIV/AIDS, due to control of infection by highly active antiretroviral therapy (HAART)1, there has been evidence of an increased frequency of cardiovascular disease of atherosclerotic origin in this group, probably due to the combination of chronic viral infection and the side effects of antiretroviral drugs, which results in metabolic disorders (glucose intolerance, dyslipidemia, lipoatrophy) and endothelial damage2. Thus, the onset of hypertension would bring an additional risk factor for the cardiovascular system or, it would constitute, in itself, a consequence of the vascular damage determined by the HIV.
The data on the prevalence of systemic arterial hypertension (SAH) in patients with HIV/AIDS vary. Even though some authors have reported higher prevalence of high blood pressure3 and systemic arterial hypertension4 in this group, compared to the prevalence of SAH in subjects without infection, other studies have found similar prevalence of SAH between men and women with HIV and individuals without the infection4-6. Another aspect that also shows different results is the role of antiretroviral drugs in the genesis of SAH. Even though some authors4,7,8 have found a relationship between SAH and the longer time of use of antiretroviral drugs and the use of regimens containing protease inhibitors, other studies5,6,9 found no association between the onset of SAH and the use or employment of an antiretroviral regimen. In Brazil, these data are even scarcer, with the study by Diehl et al2, which was conducted in the city of Londrina, state of Paraná, and which showed 32% prevalence of hypertension in HIV positive patients treated as outpatients2, and the work of Magalhães et al10, who showed 41.4% prevalence of hypertension in HIV-infected individuals over the age of 5010.
The purpose of this work is to verify, diagnose and classify SAH in adult patients included in a cohort of patients living with HIV/AIDS, and to estimate the prevalence of risk factors and epidemiological characteristics present in hypertensive patients.
This is a cross-sectional study in progress in the city of Recife, state of Pernambuco, which is aligned with a cohort for the study of cardiovascular disease and metabolic disorders in individuals over the age of 18 with HIV/AIDS. The study was conducted from June 2007 to December 2008 and it included a baseline analysis of the first 1,000 patients included in the cohort. The subjects were treated in outpatient clinics of Oswaldo Cruz Hospital, of Pernambuco University, and in the outpatient clinics of Correa Picanco Hospital, of the Health Department of Pernambuco State, consecutively selected. They completed a questionnaire and their blood pressure (BP), weight, height and waist circumference were measured by trained technicians. A data collection form was filled out with information, contained in medical records, about how long the person had had the HIV infection, type of antiretroviral treatment, viral load and CD4 lymphocyte counts. A blood sample was collected for testing blood glucose, cholesterol and triglyceride levels.
To measure the blood pressure, we used a BDTM stethoscope and a MissouriTM mercury column sphygmomanometer, duly calibrated by INMETRO (Brazilian Institute of Metrology, Standardization and Industrial Quality). The diagnosis of SAH was confirmed on a second visit, paid after an interval of up to two months. On both visits, two measurements of the blood pressure were made on one of the upper limbs, and in the end, the mean systolic and diastolic pressures were used. The SAH was classified according to the classification of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7)11, which considers four levels, in mmHg: normal (systolic BP < 120 and diastolic BP < 80); prehypertension (systolic BP between 120 and 139 or diastolic BP between 80 and 89); stage 1 hypertension (systolic BP between 140 and 159 or diastolic BP between 90 and 99) and stage 2 hypertension (systolic BP > 160 or diastolic BP > 100)11.
The body mass index (BMI) was calculated by using the BMI formula = [weight (kg)] / [height (m)2]. Regular physical activity was defined as the practice of physical activity during work breaks or leisure time, calculated by the metabolic equivalent of the last week of the interview, according to the International Physical Activity Questionnaire (IPAQ)12. All subjects who reported being a smoker at the time of the interview were considered smokers, regardless of the quantity of cigarettes. The consumption of alcohol was classified according to the standardized questionnaire intended for this purpose.
This study was approved by the Research Ethics Committee of Pernambuco University.
The statistical analysis of the data was carried out by using the statistical software "R" (The R Project for Statistical Computing: www.r-project.org). For a comparative analysis of the categorical variables, we applied the chi-square test, and, when necessary, the Fisher's exact test. For the comparative analysis of continuous variables, we used the Student's t-test. p values < 0.05 indicate statistical significance13.
One thousand (1,000) individuals with HIV/AIDS were consecutively evaluated. There was the loss of three patients (0.3%), because they were pregnant and 39 patients (3.9%) were excluded because the BP of such patients had been measured only once. Thus, the universe of this study consisted of 958 subjects. Out of this total, 584 patients (61%) were male and 374 were female (39%); 50% of them were 40 years-old or younger, and the other half were over 40 years of age. The average age of the cohort was 39.58 ± 10.03 years.
Figure 1 shows the distribution of respondents according to the classification of BP levels and the categories of hypertension. Among the individuals evaluated, 388 (40.5%) had blood pressure within the normal range, 325 (33.9%) were considered prehypertensive, and 245 (25.6%) were considered hypertensive. One hundred and seventy-two patients (70.2%) knew they had hypertension, and 95 of them (38.8%) used antihypertensive medication on a continuous basis. The blood pressure levels were controlled in only 36 (20.9%) patients that knew that they were hypertensive.
Out of the total of hypertensive patients, 156 (63.7%) were men, 145 (59.2%) were of mixed race; 63 (25.7%) were white; and 28 (11.4%) were black; 174 (71.0%) had a family history of SAH. Fifty-six (56) patients (23.1%) smoked, 139 (57.7%) ate fruit on a daily basis and 171 (71.2%) ate vegetables on a daily basis (Table 1).
Ninety-five (95) patients (46.1%) had lipodystrophy; 95 (38.8%) were overweight; and 34 (13.9%) were obese. The waist circumference was increased, according to criteria of NCEP-ATP III, in 72 (29.5%) patients and, according to the IDF's criteria, in 126 (51.6%) patients. Table 2 shows that, in relation to dyslipidemia, the total cholesterol level was > 200 mg% in 43 (30.9%) patients, the LDL-cholesterol level was > 130 mg% in 24 (22.0%), the HDL-cholesterol level was < 40 mg% in 75 (52.1%), the triglyceride level was > 150 mg% in 84 (60.0%) and the glucose levels were > 110mg/dl in ten patients (7.1%).
The viral load was undetectable or < 10,000 copies in 54 patients (80.6%) and the CD4 lymphocyte levels were > 350 cells/mm3 in 80 patients (63.5%). Antiretroviral drugs were used in 184 patients (85.9%) and protease inhibitors (PI) in 89 (41.6%). However, 95 patients (44.4%) did not use PI. Approximately 127 patients (74.7%) had been using antiretroviral drugs for more than 24 months (Table 3).
A comparison between hypertensive and prehypertensive patients showed similarity in most risk factors, except for the fact that hypertensive patients were older, they had more cases of hypertension in their families, their waist circumference was larger, and their body mass index and triglyceride levels were higher. The physical activity of prehypertensive patients was more intense (Figure 2 and Tables 1, 2 and 3). With respect to the parameters related to HIV infection and treatment, such as viral load, CD4 lymphocyte counts, the use of antiretroviral drugs, the type of antiretroviral regimen and duration of use, there was no difference between hypertensive and prehypertensive patients (Table 3).
This study included 958 HIV-infected individuals, most of whom were patients that had been previously diagnosed with AIDS and who had used antiretroviral drugs for more than 24 months. The study also revealed prevalence of 25.6% of hypertension and 33.9% of pre-hypertension. Even though most patients included in the study had already developed AIDS, the average CD4 lymphocyte count was 470 cells, and 80.6% of patients had a low or undetectable viral load. These data strongly suggest the effective use of antiretroviral drugs. Conversely, in relation to hypertension, the SAH was controlled in only 14.7% of hypertensive patients.
The newest edition of JNC 711 categorized blood pressure into normal, prehypertension, "stage 1" hypertension and "stage 2" hypertension. The new "prehypertension" category is a warning to physicians and patients, because it was found that the cardiovascular morbidity and mortality begin with these values or even at lower values11. In our cohort, the blood pressure level of a large portion of individuals living with HIV/AIDS, i.e., 325 (33.9%), was within the pre-hypertension range, which indicates the importance of providing this population with guidance on how to lead a healthy lifestyle.
With respect to the prevalence of SAH, two important studies were conducted in Brazil to assess the prevalence of SAH in the general population. The first one deals with the compilation of studies on the prevalence of hypertension in different genders and age groups in different regions of Brazil, conducted between 1993 and 200414. The second one, called "Hearts of Brazil" and conducted by the Brazilian Society of Cardiology, prospectively evaluated 2,550 individuals of different age groups, in several cities in Brazil from 2005 onwards15. In both studies, there was an overall prevalence of hypertension in about 28.5% of the individuals, and the highest prevalence was in the Northeast, where it reached 31.8%. Thus, one can conclude that the prevalence of SAH in patients with HIV/AIDS that accounted for 25.6% in this study was not different from that found in the Brazilian population.
In an Italian study that included 287 HIV-positive patients, who were on HAART, there was prevalence of 34.2% against 11.9% in patients in the control group (p < 0.0001)9. In the study called Data Collection on Adverse Events of Anti-HIV Drugs (DAD, 2005), a leading international cohort, it was concluded that high blood pressure in HIV-infected individuals is associated with traditional risk factors for hypertension9. There was no evidence of a risk associated with any of the classes of antiretroviral drugs9, although the use of NNRTI is "traditionally" associated with a low risk of developing hypertension. In the African study (Women's Interagency HIV Study, 2007)6 conducted with a cohort composed of only HIV positive women, the prevalence of hypertension in 1,266 HIV-positive women was similar to the prevalence of hypertension in 368 HIV-negative women (26 versus 28%, p = 0.3800). In a recent study conducted in 20084, in a Norwegian cohort of 542 individuals with HIV/AIDS, hypertension was prevalent in 36.5% of the individuals, which is similar to the general population. A study in Spain16 detected high prevalence of hypertension in the HIV group (25% versus 15%, p < 0.001) when compared to HIV-negative control patients.
With respect to the treatment of HIV infection in this study, it was found that the prevalence of PI-containing regimens in hypertensive patients was 41.6%, and the prevalence of regimens without PI was 44.4%. With respect to the type of antiretroviral regimens (containing PI or NNRTI) involved in the genesis of the SAH, even though the proportion of use of PI was greater among hypertensive patients than in the general population infected, the study design used does not allow reaching conclusions about the theme. It was also possible to notice that the use of different antiviral regimens, i.e. simple or complex regimens, does not preclude adherence to antiretroviral therapy, whereas the treatment of hypertension, in general, arouses less interest of the patient and even of the assistant physician, which explains why the hypertension was controlled in only 14.7% of the patients. It is a disease that is usually oligosymptomatic/asymptomatic and which, due to its high prevalence in the population, certainly creates less fear and fewer fantasies of death than the HIV.
Several lifestyle factors are likely to have a direct influence on blood pressure levels, both from the perspective of individuals and from the perspective of the population. Among these, the most important lifestyle factors are excess body fat (overweight/obesity), alcohol consumption, insufficient physical activity, smoking, stress and a variety of dietary components17, such as inadequate consumption of fruits and vegetables18.
Knowing that smoking is an established risk factor for hypertension, if one observes Table 1, one will see that there is 23.1% prevalence of smoking in the sample, which is close to values found in another study in the Brazilian population14. A study with individuals with HIV/AIDS and patients with angina pectoris19 detected 24% of total prevalence of smokers in Pernambuco State, while Pupulin et al. found a rate of 35% in Paraná State20.
The high prevalence of overweightness (overweightness/obesity) (52.7%) in this population of hypertensive patients with HIV/AIDS is in line with the alarming rates of overweightness described in the literature, which showed the prevalence of 53.7 to 58% of individuals with BMI above 25 in different populations21,22. Among Brazilian workers, there was high prevalence of overweightness (approximately 46%) and SAH (approximately 30%), mainly among males23.
The guidelines of JNC 711 recommend doing least thirty minutes of physical exercises on most days of the week. In our sample of 245 hypertensive patients, 129 of the respondents (52.6%) reported not doing physical exercises (inactive/little active), and only 106 of the total (47.4%) reported doing physical exercises on a regular basis (high/moderate physical activity). Other authors also found high prevalence of sedentary lifestyle in our country, ranging from 31.8% for adults to 58.0% for the elderly in the general population24. There was significant difference between the physical activity levels of hypertensive patients and the levels of prehypertensive patients in this study, indicating that physical activity could be protecting, also in this population, against the emergence of higher pressure levels.
In this study, alcohol dependence or heavy consumption of alcoholic beverages was reported by 27 of the hypertensive patients (11.8%) and 45 of the pre-hypertensive patients (14.8%), with no difference between the groups. The excessive consumption of alcoholic beverages is associated with SAH, and the restriction of alcohol intake can lower blood pressure25,26, which is a modification of lifestyle recommended by JNC 711.
With respect to the time when the hypertension was diagnosed, more than half (54.4%) learned they had hypertension after the HIV diagnosis, and many (29.8%) did not know they had hypertension before this study was conducted. Moreover, only 21% of patients who knew they were hypertensive had their blood pressure levels adequately controlled. These findings seem to indicate that the patients were not warned by infectious disease specialists about the fact that they had hypertension, or that neither the patients nor the doctors had learned of the hypertension diagnosis, due to the "virological dictatorship," i.e., all concerns are aimed at controlling the HIV. Or rather, the prolonged use of antiretroviral drugs could have been the determining factor for the onset of hypertension, which is an aspect that seems unlikely given the data presented here.
In conclusion, the evaluation of a population with HIV/AIDS, according to the new international classification of JNC 7, revealed prevalence of prehypertension and hypertension in over half of the population. It is important to warn clinicians who provide care to HIV/AIDS patients that such patients are not only individuals infected with a potentially fatal virus, but, despite the benefit of new antiretroviral therapies, they are also patients whose prognosis may be affected by comorbidities, such as hypertension.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Sources of Funding
This study was funded by Programa Nacional de DST/AIDS - Ministério da Saúde.
This article is part of the thesis of master submitted by Evanízio Roque de Arruda Júnior, from Universidade Federal de Pernambuco.
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Mailing address: Manuscript received April 22, 2009; revised manuscript received February 26, 2010; accepted April 28, 2010.
Evanizio Roque de Arruda Junior
Av. João Maurício, 1229 - Manaíra
58038-000 - João Pessoa, PB - Brazil
Manuscript received April 22, 2009; revised manuscript received February 26, 2010; accepted April 28, 2010.