Biochemical markers of hypertension and chronic renal failure in a Gulf Arab population of the United Arab Emirates

Abstract

Hypertension is the commonest cardiovascular disorder and poses a major health challenge to populations of countries in socio-economic transition as well as those of developed countries. In the United Arab Emirates (UAE), hypertension has emerged as a leading cause of death. However, there is little first hand information with regard to the status of specific known risk factors for hypertension, nor of the extent to which the rapid changes in life style, especially dietary habits and lack of exercise, have contributed to the growing number of hypertensives in this population. The aim of this study was to document the circulating levels of various biochemical markers of hypertension and chronic renal failure (CRF), a disease which is normally associated with hypertension. The study population consisted of hypertensive and CRF patients and healthy
Emirati subjects, who are mainly Gull Arabs of Bedouin descent. It has been hypothesized that the population lacks a number of confounding risk factors for cardiovascular diseases such as alcohol consumption, chronic stress and cigarettesmoking.
Plasma levels of immunoreactive endothelin-1 (ET-l), homocysteine (Hcy), growth hormone (GH), insulin-like growth factor-I (IGF-l), leptin, and insulin were measured by standard enzyme-linked immunosorbent assay (ELISA) methods. Plasma
glucose, blood urea nitrogen (BUN), creatinine, lipids and lipoproteins were measured by standard colorimetric assays.
With regard to hypertension, a major finding of this study is related to the levels of ET-1 in Etniratis with untreated essential hypertension. These were significantly (p < 0.01) higher in hypertensives (mean 10.1 ± 1.0 pmol ') than in normotensives (mean 2.2± 0.5 pmol F'). For all subjects ET-1 levels correlated closely with systolic blood pressure (SBP), but less significantly with diastolic blood pressure (DBP) and body weight. In a more extensive study, hypertensives were found to have higher body mass index (BMI) and triacylglycerols (TG), non-esterified fatty acids (NEFA) and ET-1 and
lower high-density lipoprotein- (HDL)-cholesterol. Further, both SBP and DBP weresignificantly correlated with age, BMI. NEFA, ET-1 and log insulin and TG and negatively with HDL-cho!esterol. The independence of associations between blood
pressure and ET-1 or HDL-cholesterol and ET-1 and HDL-cholesterol or NEFA were confirmed by partial regression, but not that of correlations between NEFA and blood pressure or HDL-cholesterol. Further study of the racial differences in the levels of biochemical markers among treated hypertensive subjects of four ethnic groups, has revealed that whilst ET-1 was decreased to normal levels. Hcy was significantly increased in hypertensives than age-, gender- and ethnic-matched healthy normotensives. In all hypertensive subjects, total cholesterol (TC), HDL-cholesterol, and low-density lipoprotein- (LDL)—cholesterol were significantly decreased and TG was significantly increased while NEFA was unchanged. Emirati subjects, either hypertensives or normotensives, had the highest BMI with tendency towards obesity compared to the non-
Gulf Arab, African, and Asian groups respectively. In patients with renal disease, results have shown that IGF-1 is notably decreased in CRF patients and negatively correlated with both systolic and DBP indicative of a possible role for IGF-1 as a marker of renal disease progression among hypertensive patients. Moreover, significantly elevated levels of leptin were observed, particularly in female patients, and leptin was shown to correlate significantly (p < 0.0]) with insulin,
total and LDL-cholesterol and TG. Leptin was negatively correlated with GH concentrations, but was not correlated with IGF-1 levels. Further, the results have also shown that in CRF, reduced activity of lecithin: cholesterol acyltransferase (LCAT), has been documented and this has been shown to be associated with low levels of HDLcholesterol
and other lipid changes including membrane lipid composition. in untreated hypertensives, low I-IDL-cholesterol have also been documented, but apparently without impaired LCAT activity. When combined all CRF subjects, regardless of dialysis, total and LDL-cholesterol were unchanged, TO and free cholesterol (FC) were raised and HDL-cholesterol levels and the percentage of esterified cholesterol (EC) were significantly decreased compared to controls. Plasma NEFA levels for untreated patients were similar to controls, but were decreased in peritoneal dialysis patients and markedly increased both before and, even more so, after dialysis in haemodialysis patients. In conclusion, the results of this study have shown that plasma concentrations of ET-1 in Emiratis are significantly (p c 0.01) higher in untreated hypertensives than in
normotensives. The increased lelevls of FT-I were associated with raised NEFA and decreased HDL-cholesterol concentrations. It is suggested that ET-1 either alone or in conjunction with dislipidaemia, could be a risk factor for cardiovascular disease in this population. in treated hypertensive subjects however, Hcy levels rather than FT-I were
increased in all ethnic groups compared to age- gender and ethnic-matched controls. In addition, the pattern of correlations and hormone and lipid changes found in this study suggest that raised insulin levels may be an important determinant of leptin levels in CRF, but that OH, IGF-1 and lipid status are not.