Arterial stiffness AIx (75) was significantly raised in HIV patients both treated and treatment naïve compared to HIV negatives when all the participants were taken into account (Table 1 and Figure 5). This is in agreement by the study reported by Falasca [18
], who compared HIV patients and non-infected subjects. Compared with uninfected subjects, HIV-infected subjects in their study had higher PWV and AIx (75) values.
We also took note of the fact that the groups had significant differences in their age groups. When we looked at the age range 35years and below, the AIx in the differences in the Augmentation index were not significant and the significance in the overall participants might be due to the age differences. Some other studies have also referred to arterial stiffness as being affected by age [19
]. The present study showed positive correlations of arterial stiffness with age in the controls and HAART naïve participants. These findings are also in agreement with studies previously reported in HIV children by measuring their carotid arterial stiffness [21
] studied 83 HIV-infected children with a mean age of 1.0 ± 3.1 years and 59 controls aged 12.2 ± 2.8 years. Among the HIV-infected children, 48 were receiving HAART (23 including a protease inhibitor). HIV-infected children had increased arterial stiffness compared with healthy children. These changes were more pronounced with increasing age in HIV-infected children particularly in those who were receiving HAART. Mitchell [22
] in the Framingham study reported that with advancing age, arterial stiffness and wave reflections increase and elevate systolic and pulse pressures. Mention must also be made of the fact that the Augmentation index in the females were also increased, This might be due to reduced height in females compared to males which leads to increased augmentation index.
In this study, SEVR% was highest in the HIV negative participants and lowest in HAART naive participants (Table 1 and Figure 5). The decrease in SEVR in the two groups of HIV positive patients (p<0.001) observed in the present study may be due to endothelial dysfunction affecting the coronary arteries. Increased immune activation and inflammation reported in chronic HIV-infection as well as the characteristic dyslipidemia associated with HIV infection and antiretroviral therapy (ART) also contribute to an increased risk of atherosclerotic vascular disease among HIV-infected adults [22
In the older age group, this might be due to atherosclerosis. There is also premature biological aging in HIV-infected patients [23
]. This will now cause decreased myocardial perfusion [24
]. In normal coronary arteries, subendocardial ischemia occurs when SEVR% falls below 50% [25
]. The findings of this study were that SEVR was decreased significantly in the two groups of HIV participants (p<0.001) whilst ED% was higher in the HIV participants. Low SEVR% has been shown to be associated with coronary artery disease [23
]. Estimation of SEVR by using applanation tonometry may provide a reliable tool for the assessment of coronary microcirculation in essential hypertensives with indications of myocardial ischemia and normal coronary arteries [23
]. This might also be used in HIV positive subjects. To rule out the effect of aging on these results, participants who were aged 35 years and below were analysed. After adjusting for confounding factors (MP, waist-Hip ratio, study status group-HIV negatives-HIV positives on ART-HIV positives on ART, and ages) and using multiple linear regression analysis, only increase in HR (P<0.0001) and female gender(P=0.048) significantly and independently predicted decrease in SEVRS% as follows. Thus, the effect of age was sort of cancelled Y=292.688-0.727 × HR-0....162× Gender (Male=1 and Female=2). Thus increase in heart rate decreased the SEVR. Females were also found to have a lower SEVR than males (p<0.000).
Although age is a predictor for all the participants including those that are over 35 in our study it is not a determining factor in participants below the age of 35 years. The fact that females can also predict SEVR having a lower value makes females more prone to myocardial ischemia. Women have smaller and stiffer blood vessels resulting in an earlier return of the reflected wave, which is likely due to an increased pulse wave velocity in women contributing to their increased augmentation index compared to males (Table 4), This can lead to increased arterial stiffness [25
]. The tonometric sub-endocardial viability ratio (SEVR) is impaired in the HIV positive participants in this study. In HIV positive participants there was also significant arterial stiffness compared to HIV negative participants. This shows that increased aortic stiffness and decreased subendocardial viability ratio predisposes to myocardial ischemia by increasing the systolic tension-time index and by decreasing aortic pressure throughout diastole. Thus the HIV positive participants are prone to having myocardial infarction or stroke because of the impaired oxygen supply to the heart.
Endothelial dysfunction has emerged as one of the major mechanisms underlying the increased cardiovascular disease risk seen in the HIV population . Endothelial progenitor cells, circulating endothelial cells, endothelial micro particles, and platelet micro particles are all now considered as biomarkers of cardiovascular disease risk in otherwise healthy individuals [26
]. In normal coronary arteries, subendocardial ischemia occurs when SEVR% falls below 50% [27
]. The findings of this study were that SEVR was decreased significantly in the two groups of HIV participants (p<0.001) whilst ED% was higher in the HIV participants.
The ratio of the duration of systolic ejection to the total duration of a cardiac cycle is the ejection duration index (ED %) [29
]. The HIV positive participants in this study have higher ejection duration index ED%. The ED% was lowest in the HIV negative participants and highest in those that are not on treatment (p<0.001). This might indicate that the HIV positive participants not on treatment were at a higher risk of developing cardiovascular problems such as systolic dysfunction
. ED% was also higher in females than males [29
]. This might be because females have higher Augmentation index therefore lower heart rate and therefore lower ejection index [30
]. This shows that increased aortic stiffness and decreased subendocardial viability ratio predisposes to myocardial ischemia in HIV positive participants. This could be due to increasing the systolic tension–time index and by decreasing aortic pressure throughout diastole. Thus the HIV positive participants are prone to having myocardial infarction or stroke because of the impaired oxygen supply to the heart. From this study there was also no significant correlation in healthy subjects, in the SEVR between the age groups and in both males and females (p<0.05 for both). There was also no correlation between SEVR and age, CD4 count in all the groups. We also observed significant arterial stiffness in HIV positive participants when compared to HIV negative participants (p=0.024) (Table 1).
Smoking both had negative correlations on SEVR in the HIV negative participants (Table 5); Heart rate also had negative correlation with SEVR in all the groups of participants. This was more with HIV participants who were already on treatment (p=0.000 and p=0.02). This could be because those on treatment knew they were already positive, whereas the other group is not aware until they were tested. They might be using the smoking habit and alcohol intake to allay their fears.
The study has some limitations. First, the cross-sectional design did not allow the investigation of some abnormalities in arterial properties. Longitudinal studies are needed to clarify this. Also matching for age and gender and other potential risk factors was not successful in all cases. The study started with 300 enrolled participants of which only 169 finished although this was anticipated. Although the duration of anti-retrovirals
used were asked in the questionnaire many of the participants could not give the exact date of commencement and hence it was not used in the study. Though exercising habit was recorded it was also not included in the analysis. This study has shown that HIV virus contributes to arterial stiffness and cardiac functions. This could be prevented if these indices are monitored and preventive measures such as statins given to these patients. It is also possible that in the older age group, age is a predictor of SEVR but not a determining factor in those participants under 35 years.