Increased renal resistance detected by ultrasound (US) Doppler has been reported in severe essential hypertension (EH) and recently was shown to correlate with the degree of renal impairment in ...hypertensive patients with chronic renal failure. However, the pathophysiological significance of this finding is still controversial.
In a group of 211 untreated patients with EH, we evaluated renal resistive index (RI) by US Doppler of interlobar arteries and early signs of target organ damage (TOD). Albuminuria was measured as the albumin to creatinine ratio (ACR) in three non-consecutive first morning urine samples. Left ventricular mass was evaluated by M-B mode echocardiography, and carotid wall thickness (IMT) by high resolution US scan.
RI was positively correlated with age (r=0.25, P=0.003) and systolic blood pressure (SBP) (r=0.2, P=0.02) and with signs of early TOD, namely ACR (r=0.22, P=0.01) and IMT (r=0.17, P<0.05), and inversely correlated with renal volume (r=-0.22, P=0.01) and diastolic blood pressure (r=-0.23, P=0.006). Multiple linear regression analysis demonstrated that age, gender, ACR and SBP independently influence RI and together account for approximately 20% of its variations (F=8.153, P<0.0001). When clinical data were analysed according to the degree of RI, the patients in the top quartile were found to be older (P<0.05) and with higher SBP (P<0.05) as well as early signs of TOD, namely increased ACR (P<0.002) and IMT (P<0.005 by ANOVA), despite similar body mass index, uric acid, fasting blood glucose, lipid profile and duration of hypertension. Furthermore, patients with higher RI showed a significantly higher prevalence of microalbuminuria (13 vs 12 vs 3 vs 33% chi2=11.72, P=0.008) and left ventricular hypertrophy (40 vs 43 vs 32 vs 60%, chi2=9.25, P<0.05).
Increased RI is associated with early signs of TOD in EH and could be a marker of intrarenal atherosclerosis.
Microalbuminuria is defined as abnormal urinary excretion of albumin between 30 and 300 mg/d. It can be measured accurately by several widely available and sensitive methods. This abnormality can be ...found in 8 to 15% of nondiabetic patients with primary hypertension, although its prevalence varies greatly in the literature, likely due to differences in the methods used to detect it and to the criteria applied in the selection of patients. The pathogenetic mechanisms leading to the development of microalbuminuria are still not completely known. BP load and increased systemic vascular permeability, possibly due to early endothelial damage, seem to play a major role. Increased urinary albumin excretion has been associated with several unfavorable metabolic and nonmetabolic risk factors and subclinical hypertensive organ damage. In fact, a higher prevalence of concentric left ventricular hypertrophy and subclinical impairment of left ventricular performance, as well as the presence of carotid atherosclerosis, have been reported in patients with microalbuminuria. These associations might per se justify a greater incidence of cardiovascular events. Long-term longitudinal studies have recently confirmed the unfavorable prognostic significance of microalbuminuria in hypertensive patients. It has also been hypothesized that microalbuminuria might be a forerunner of overt renal damage in primary hypertension. Clinical studies, however, have shown conflicting results, and this hypothesis has to be considered tempting but speculative at present. In conclusion, microalbuminuria is a specific, integrated marker of cardiovascular risk and target organ damage in primary hypertension and one that is suitable for identifying patients at higher global risk. A wider use of this test in the diagnostic work-up of hypertensive patients is recommended.
Ultrasound (US) examination of heart and carotid arteries provides an accurate assessment of target organ damage (TOD) and may influence the stratification of the absolute cardiovascular risk ...profile. Microalbuminuria has recently proved to be a useful cost-effective marker of increased cardiovascular risk but is still too often neglected in clinical practice.
To evaluate how well artificial neural networks (ANNs) predict cardiovascular risk stratification by means of routine data and urinary albumin excretion, as compared to prediction by the clinical work-up suggested by the International Society of Hypertension (ISH), with and without ultrasound-determined TOD.
A group of 346 never previously treated essential hypertensives (212 men, 134 women, mean age 47 +/- 9 years) was studied. Risk was stratified according to the criteria suggested by the 1999 WHO/ISH guidelines; first, by routine procedures alone, and subsequently by reassessment, using data on cardiac and vascular structures obtained by US evaluation. The ANN was trained and tested to predict the overall cardiovascular risk on the basis of routine clinical data and urinary albumin excretion (UAE). The impact of these three approaches on the determination of cardiovascular risk profile was evaluated.
According to the first classification, 5.5% (n = 19) of patients were considered at low risk, 47.3% (n = 164) at medium, 26.7% (n = 92) at high and 20.6% (n = 71) at very high risk. A marked change in risk stratification, namely an increase in the prevalence of high- and very-high-risk patients (2.3% low, 29.8% medium, 42.8% high and 25.2% very high risk; chi(2) 15.201, P < 0.0001), was obtained when US examination of TOD was taken into consideration. On the basis of routine clinical data and UAE, the artificial neural network successfully predicted overall cardiovascular risk and allocated patients in different classes as accurately as the US-based evaluation.
The use of US techniques allows a more precise stratification of absolute cardiovascular risk in hypertensive patients as compared to routine clinical data. An ANN can accurately identify the patients' risk status by using low-cost routine data and UAE. These results further emphasize the value of UAE in the stratification of cardiovascular risk.
Microalbuminuria, a powerful predictor of cardiovascular events, is thought to reflect widespread subclinical vascular abnormalities. To explore the pathogenesis of increased urinary albumin ...excretion in primary hypertension we evaluated systemic capillary permeability and ambulatory blood pressure (BP) measurement in two groups of matched untreated patients with (
n = 11) and without (
n = 29) microalbuminuria.
Albuminuria was measured as the mean of albumin-to-creatinine ratio (ACR) in three nonconsecutive first morning urine samples. Systemic capillary permeability was evaluated by transcapillary escape rate of albumin (TERalb) (ie, the 1-h decline rate of intravenous
125I-albumin). Twenty-four-hour ambulatory BP, renal hemodynamics, and hormones of the renin-angiotensin-aldosterone system (RAAS) were also assessed.
Patients with microalbuminuria showed greater body mass index (BMI) (
P < .04), higher 24-h systolic and diastolic BP levels (
P = .02), and higher capillary permeability to albumin (
P < .02) as compared to normoalbuminurics. Renal hemodynamics and RAAS hormones were similar in the two groups. Univariate analysis showed that urinary ACR was related to ambulatory pressure components (
P < .02), TERalb (
r = 0.31,
P < .05), smoking habits (
r = 0.36,
P = .02), and left ventricular mass index (LVMI) (
r = 0.57,
P < .001) among the whole study group. Logistic regression analysis showed that each 1% increment in TERalb or 10 mm Hg increase in systolic BP entailed an almost three times higher risk of having microalbuminuria.
Microalbuminuria is associated with greater systemic BP load and increased vascular permeability in patients with primary hypertension.
Mild renal dysfunction, defined as GFR <60 to 70 ml/min and/or the presence of increased urinary albumin excretion, is associated with higher cardiovascular morbidity and mortality in primary ...hypertension. The aim of the present study was to investigate the relationship between renal dysfunction and target organ damage (TOD), namely left ventricular hypertrophy (LVH), retinal vascular changes, and carotid atherosclerosis, in a large cohort of unselected middle-aged hypertensive patients with normal serum creatinine. A group of 934 untreated patients with primary hypertension (543 men, 391 women; mean age 50 +/- 11 yr) was studied. Renal function was estimated by the creatinine clearance using the Cockcroft-Gault formula and by the presence of albuminuria, measured as the albumin to creatinine ratio (A/C) in first morning urine samples. LVH was determined according to electrocardiographic criteria, and retinal vascular changes were evaluated by direct ophthalmoscopy in all patients. In a subgroup of patients (n = 340; 208 men, 132 women; mean age 47 +/- 9), the presence and extent of cardiac and vascular organ damage was also assessed by ultrasound techniques. Creatinine clearance was on the average 82 +/- 20 ml/min. The overall prevalence of ECG-detected LVH and retinopathy was 12 and 49%, respectively. Creatinine clearance was inversely related to duration of disease, systolic BP, serum glucose, total cholesterol, LDL cholesterol, and early signs of TOD, namely retinal vascular changes and LVH. Patients in the bottom quintile of creatinine clearance showed higher prevalence of both ECG-determined LVH (P = 0.04) and retinal vascular changes (P = 0.02). In the subgroup of patients who underwent ultrasound evaluation of cardiovascular structures, the prevalence of mild renal dysfunction was 18%, whereas the prevalence of LVH and carotid plaque was 49 and 26%, respectively. Patients with mild renal dysfunction showed higher left ventricular mass and increased intima-media thickness (P < 0.0001), as well as higher prevalence of LVH and carotid plaque as compared with those with normal renal function. Controlling for duration of hypertension and mean BP, the risk of TOD in our cohort increased by 20% for each 10 ml/min decrease in creatinine clearance and by 30% for each 0.2 mg/mmol increase in Log A/C. In conclusion, mild renal dysfunction is associated with preclinical end-organ damage in patients with primary hypertension. These data may help to explain the observed increase in cardiovascular mortality reported in these patients. The evaluation of creatinine clearance and urinary albumin excretion could be useful for identifying patients who are at higher cardiovascular risk.
Hyperhomocysteinemia is a known risk factor for the development of atherosclerotic vascular damage. Plasma homocysteine levels are influenced by nutritional and hereditary factors. A point mutation ...(cytosin to thymidine substitution; C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) makes the enzyme thermolabile and has been associated with elevated homocysteine levels in homozygous carriers (TT genotypes). We evaluated the relationship between the T allele encoding for the thermolabile variant of MTHFR and several biochemical risk factors and early signs of hypertensive and atherosclerotic organ damage in 206 untreated patients with EH. MTHFR genotype was evaluated by PCR. Albuminuria was measured as albumin to creatinine ratio (ACR) in three non consecutive urine samples. Microalbuminuria was defined as an average ACR between 2.38–19 (males) and 2.96–20 (females). LV mass index (LVMI) was assessed by M-B mode echocardiography (g/m2), carotid geometry by high resolution US scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of Alb+, LVH and retinopathy was 14, 45 and 42% respectively. The prevalence of carotid plaque was 25%. Genotype frequencies were CC 29, CT 54, TT 17% according to Hardy Weinberg equilibrium. Clinical and biochemical characteristics of patients and LVMI and ACR were similar when analyzed on the basis of MTHFR genotype. Patients with TT polymorphism showed a higher prevalence of retinal vascular changes (P < 0.02) and carotid plaque (P < 0.05). Moreover, patients with T allele showed increased carotid artery size as demonstrated by intima plus media thickness (TT, 0.79 ± 0.05 vs CT + CC, 0.67 ± 0.02 mm; P < 0.02), relative wall thickness (TT, 0.23 ± 0.01 vs CT + CC, 0.20 ± 0.005; P < 0.02) and surface area (TT, 19 ± 1.9 vs CT + CC, 15 ± 0.55 mm2; P < 0.05). Multiple linear regression analysis demonstrated that MTHFR genotype and systolic blood pressure independently influence IMT and together account for about 11% of its variations (r2 = 0.11, F = 9.7, P < 0.0001). Homozygosity for the T allele of the MTHFR gene is an independent risk factor for the development of early atherosclerotic organ damage in hypertensive patients.
Different classes of antihypertensive drugs might convey specific organ protection independently of blood pressure (BP) lowering effect. To test this hypothesis we evaluated the effects of ...antihypertensive treatment with Losartan (L) as compared to Felodipine (F), in monotherapy or combined with Chlortalidone (C) on blood pressure, urinary albumin excretion (UAE) and left ventricular mass index (LVMI) in patients with mild to moderate essential hypertension (EH). BP, UAE were evaluated at baseline and after 1, 2, 3, 6 and 12 months of treatment; LVMI at baseline and 12 months thereafter. Forty-six hypertensive patients (24 m, 22 f) were randomized to receive either F (n=22) or L (n=24). UAE was evaluated as the albumin to creatinine ratio (ACR, mg/mmol) in three consecutive first morning urine samples (negative urine culture); LVMI by M-B echocardiography. Patients characteristics at baseline were similar between the two groups of treatment. Both L and F effectively reduced BP levels at 1, 2 3 and subsequently at 6 and 12 months (MAP 120±2 at baseline, 105±2 mmHg at one year in the L group; MAP 121±2 at baseline, 104±1 at one year in the F group). The number of patients requiring diuretic therapy was similar in the two groups. UAE and LVMI were slightly although not significantly reduced after 12 months of therapy in both groups. However, when analysis of data was restricted only to patients with the highest UAE and LVMI values (i.e. those above the median) it resulted that despite similar blood pressure control, L but not F significantly reduced both UAE and LVMI (ACR 1.9±0.6 at baseline, 0.5±0.1 at one year, p<0.05 and LVMI 140±4 at baseline, 124±8 at one year, p<0.05 in the L group; ACR 2.45±2 at baseline, 1.2±0.4 at one year, NS and LVMI 137±5 at baseline, 122±10, NS in the F group). Both L and F effectively reduce BP levels in patients with EH. At similar blood pressure levels, L seems to be more effective in reducing early end organ damage. These results suggest that the renin-angiotensin system plays a significant role in the development of subclinical cardiovascular disease.
Accurate cardiovascular risk evaluation is a prerequisite for devising cost-effective therapeutic strategies in patients with essential hypertension. In fact, the knowledge of concomitant risk ...factors, diabetes, target organ damage, or associated clinical conditions may be useful when deciding both treatment and BP goals. Thorough evaluation of target organ damage is the key to sensitive assessment of global risk, but cost-effective allocation of economic resources should also be taken into consideration. Thanks to its low cost and widespread availability, the search for microalbuminuria is a first-line tool for identifying hypertensive patients who are at higher cardiovascular risk.
A cohort of 227 untreated essential hypertensive patients from north-western Italy was studied in order to evaluate the prevalence of micro- and macroalbuminuria and their relationship with other ...cardiovascular risk factors. Albuminuria was evaluated as the albumin to creatinine ratio (Alb/Cr) in three non-consecutive first morning samples. The prevalence of microalbuminuria and macroalbuminuria was 10% and 2.2%, respectively. Albuminuric patients showed higher blood pressure, serum creatinine, triglycerides and uric acid as well as a greater prevalence of retinopathy. Stepwise multiple regression analysis demonstrated that only a small part of variations in albuminuria was explained by changes in blood pressure. Duration of disease did not seem to influence microalbuminuria. The presence of hypertensive retinopathy was associated with greater albuminuria, longer duration of hypertension, and higher prevalence of major ECG changes, but not with higher blood pressure levels. Microalbuminuria, rather than a consequence of elevated blood pressure levels, seems to be a marker of a syndrome featuring, among other characteristics, essential hypertension. Furthermore, microalbuminuria must be considered as an independent cardiovascular risk factor.
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