Two-Day ABPM-Derived Indices and Mortality in Hemodialysis Patients.

BACKGROUND: Blood pressure (BP) and arterial stiffness are known cardiovascular risk factors in hemodialysis (HD) patients. This study examines the prognostic significance of 44-hour BP circadian rhythm and ambulatory arterial stiffness index (AASI) in this population. METHODS: A total of 80 HD patients underwent 44-hour ambulatory BP monitoring (ABPM) with a TM-2430 monitor during a standard midweek interdialytic interval and followed up for 4.5 ± 1.7 years. The end point was all-cause mortality. RESULTS: About 76% of participants were hypertensive (40% uncontrolled), 62% were nondippers, and 23% risers during the first interdialytic day, whereas 73% and 44% in the second day, respectively. During follow-up, 31 patients (40%) died. These showed higher pulse pressure (PP) and AASI44 and AASI of the second interdialytic period. The incidence of all-cause mortality was higher in HD patients with AASI44 > median, i.e. >0.54 (interquartile range = 14) (54% vs. 28%, χ 2 = 5.3, P = 0.021) when compared with those with lower AASI44. Second, but not first-day ABPM-derived parameters, namely nondipping (log-rank χ 2 = 6.10, P = 0.0134) or reverse dipping status (log-rank χ 2 = 5.32, P = 0.210) and arterial stiffness index (log-rank χ 2 = 6.61, P = 0.0101) were significantly related to greater mortality. CONCLUSIONS: These findings indicate a strong relationship between arterial stiffness and cardiovascular risk and support a wider use of 44-hour ABPM recording for risk stratification in HD patients.

Peripheral artery disease and blood pressure profile abnormalities in hemodialysis patients.

BACKGROUND: Patients undergoing chronic hemodialysis (HD) are at increased risk for peripheral artery disease (PAD). Both ankle-brachial index (ABI) and ambulatory blood pressure monitoring (ABPM) in the interdialytic period have been shown to be strong predictors of all-cause mortality. METHODS: This cross-sectional study investigated the relationship between ABPM profile and ABI in 81 HD patients. ABPM was measured throughout a 44-h midweek interdialytic period. Pre-dialysis ABI was evaluated with a BOSO ABI device. An ABI value <0.9 or ≥1.3 was defined as abnormal. RESULTS: In the whole study group (72 % males, mean age 67 ± 14 years), there was an increase in BP (p < 0.05) and in systolic BP night/day ratio (n/dSR, p = 0.01) during the interdialytic period. Patients with abnormal ABI (n = 29) more frequently had a positive history for cerebrovascular accident and PAD and higher proBNP values than those with normal ABI (n = 52). No difference was detected among ABPM-derived components except for the n/dSR (p = 0.02). Patients with abnormal ABI showed a significantly increased n/dSR (p = 0.02) and ambulatory arterial stiffness index (AASI) (p = 0.006) on the second day compared to the first. Patients with n/dSR >1 during day 2 (n = 34) were older, showed significantly higher proBNP and AASI and were more likely to reveal abnormal ABI compared to those with a lower n/dSR (p = 0.006). CONCLUSIONS: Abnormal ABI in HD patients is associated to changes in interdialytic ABPM pattern, namely higher n/dSR on day 2. These data may indicate the pathophysiological mechanisms underlying the worse outcome observed in HD patients.

[Hyperuricemia and renal risk]. / Iperuricemia e rischio renale.

Recent studies have revealed an association between elevated levels of uric acid and conditions correlated to chronic kidney diseases such as hypertension, cardiovascular and cerebral disease, insulin resistance. Several pathogenetic mechanisms at cellular and tissue levels could justify a direct correlation between serum uric acid levels and renal damage. Growing evidence indicating a correlation between urate lowering therapy and renal morbidity could encourage the use of urate lowering therapy in primary or secondary prevention in chronic kidney disease.

[Hyperuricemia, diabetes and hypertension]. / Iperuricemia, diabete, ipertensione: un'associazione casuale?

Hyperuricemia is frequently found in association with several condition predisposing to cardiovascular events such as arterial hypertension and diabetes mellitus. This has led researchers to investigate possible pathogenetic mechanisms underlying this association. Several experimental studies and some indirect clinical evidence support a causal link between mild hyperuricemia and the developement of hypertension as well as new onset diabetes. At the tissue level, chronic exposure to increased uric acid has been shown to promote vascular changes leading to renal ischemia as well as stimulation of the renin angiotensin system. Furthermore, uric acid has been shown to promote the development of insulin resistance, hypertrglyceridemia and haepatic steatosis through pro-oxidative mechanisms. These experimental pathophysiological changes may be partly preventable by hypouricemic treatments. Whether clinical implications of these findings are confirmed by solid clinical intervention trials, mild hyperuricemia may soon change its status from risk predictor to treatment target for patients at high cardiovascular and renal risk.

Left ventricular dilatation and subclinical renal damage in primary hypertension.

OBJECTIVE: A new classification of left ventricular geometry based on left ventricular dilatation and concentricity has recently been developed. This classification identifies subgroups differing with regard to systemic haemodynamics, left ventricular function and cardiovascular prognosis. We investigated the relationship between the new classification of left ventricular geometry and subclinical renal damage, namely urine albumin excretion and early intrarenal vascular changes in primary hypertensive patients. METHODS: A total of 449 untreated hypertensive patients were studied. Four different patterns of left ventricular hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. Albuminuria was measured as the albumin-to-creatinine ratio. Early intrarenal vascular changes, expressed as the renal volume to resistive index ratio, were evaluated by ultrasound and Doppler scan. RESULTS: Patients with concentric dilated left ventricular hypertrophy had higher albumin excretion rates (P = 0.0258) and prevalence of microalbuminuria (P < 0.0001) and lower renal volume to resistive index ratio than patients with concentric nondilated hypertrophy (P = 0.0093). Patients with eccentric dilated hypertrophy showed a higher prevalence of microalbuminuria than patients with eccentric nondilated hypertrophy (P < 0.0001). Moreover, patients with chamber dilatation showed a higher prevalence of microalbuminuria (P = 0.0002) and lower renal volume to resistive index ratio (P = 0.0107) than patients without chamber dilatation. After adjusting for potentially confounding variables, left ventricular chamber dilatation was an independent predictor of subclinical renal damage. CONCLUSION: Left ventricular dilatation is associated with subclinical renal damage in hypertension. These findings extend previous reports and provide a pathophysiological rationale for the observed unfavourable prognosis in patients with left ventricular dilatation.

Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4.

Mild hyperuricemia has been linked to the development and progression of tubulointerstitial renal damage. However the mechanisms by which uric acid may cause these effects are poorly explored. We investigated the effect of uric acid on apoptosis and the underlying mechanisms in a human proximal tubule cell line (HK-2). Increased uric acid concentration decreased tubule cell viability and increased apoptotic cells in a dose dependent manner (up to a 7-fold increase, p<0.0001). Uric acid up-regulated Bax (+60% with respect to Ctrl; p<0.05) and down regulated X-linked inhibitor of apoptosis protein. Apoptosis was blunted by Caspase-9 but not Caspase-8 inhibition. Uric acid induced changes in the mitochondrial membrane, elevations in reactive oxygen species and a pronounced up-regulation of NOX 4 mRNA and protein (p<0.05). In addition, both reactive oxygen species production and apoptosis was prevented by the NADPH oxidase inhibitor DPI as well as by Nox 4 knockdown. URAT 1 transport inhibition by probenecid and losartan and its knock down by specific siRNA, blunted apoptosis, suggesting a URAT 1 dependent cell death. In summary, our data show that uric acid increases the permissiveness of proximal tubule kidney cells to apoptosis by triggering a pathway involving NADPH oxidase signalling and URAT 1 transport. These results might explain the chronic tubulointerstitial damage observed in hyperuricaemic states and suggest that uric acid transport in tubular cells is necessary for urate-induced effects.

Early renal abnormalities as an indicator of cardiovascular risk in type 2 diabetes.

Accurate assessment of cardiovascular (CV) risk is a prerequisite for devising effective therapeutic strategies in patients with type 2 diabetes (T2DM) as it allows to refine prognosis and treatment targets as well as the cost-benefit ratio for specific pharmacological interventions. The presence of subclinical vascular organ damage plays a well known role in determining overall risk and a wider use of low cost, easy to perform diagnostic tools to stratify CV risk is very much needed. Besides their well known prognostic value for progression to end stage renal disease (ESRD), subclinical renal abnormalities such as microalbuminuria and/or a slight reduction in estimation of glomerular filtration rate (eGFR), have been shown to be powerful, independent predictors of CV diseases in patients with T2DM. Through the combined evaluation of these two biomarkers of chronic kidney disease (CKD), clinicians can usefully and reliably get a perspective on global and CV outcome of their diabetic patients.

Hyperuricemia and renal risk.

Asymptomatic mild hyperuricemia has been reported in association with a number of conditions associated with chronic kidney disease, including hypertension, insulin resistance, cerebrovascular and cardiac disease. Experimental studies indicate that serum uric acid may directly and indirectly promote renal damage by several pathogenetic mechanisms both at cellular and tissue level. While there is currently no consensus on the usefulness of urate lowering therapy with the aim of preventing chronic renal disease, growing evidence indicates a relationship between changes of serum uric acid over time and renal morbidity. The present manuscript will briefly review the evidence in favor and against an independent role for SUA in the pathogenesis of renal disease.

Effects of ACE inhibitors on long-term outcome of renal transplant recipients: a randomized controlled trial.

BACKGROUND: Available data on the role of renin-angiotensin system blockade in renal transplantation are inconclusive. Herein, we report the long-term results of a randomized controlled trial planned to evaluate the impact of angiotensin-converting enzyme inhibitors (ACE-i) on the cardiovascular outcome of renal transplant recipients (RTRs) receiving calcineurin inhibitors, steroids, and mycophenolate mofetil. METHODS: Thirty-six RTRs were allocated to receive ACE-i and 34 served as controls. Survival free of a composite endpoint consisting of death, major cardiovascular events, renal graft loss or creatinine doubling, and survival free of each single endpoint were analyzed in both groups according to a modified intention-to-treat analysis. RESULTS: During a 10-year follow-up, three patients died (one in the ACE-i group and two controls) and three lost their graft (two receiving ACE-i and one control). Three major cardiovascular events were observed in the ACE-i group and 12 among controls (P=0.008). At the end of observation, a significant increase in urinary protein excretion rate was only observed in controls (P=0.017).Compared with controls, RTRs administered ACE-i had significantly better survival free of the combined endpoint (P=0.0102, log-rank test) and free of major cardiovascular events (P=0.0027) without significant differences in renal outcome. By Cox regression analysis, ACE-i therapy resulted in the most powerful predictor of survival free of composite endpoint (hazard ratio, 0.165; 95% confidence interval, 0.053-0.512; P=0.0018) and survival free of major cardiovascular events (hazard ratio, 0.209; 95% confidence interval, 0.068-0.636; P=0.0059). CONCLUSIONS: Prolonged therapy with ACE-i was associated with better general and cardiovascular outcome of RTRs without detrimental effects on renal graft function.

Effect of early conversion from CNI to sirolimus on outcomes in kidney transplant recipients with allograft dysfunction.

BACKGROUND: Studies evaluating the effect of conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) in renal transplant recipients (RTRs) have shown conflicting results, and only few short-term uncontrolled studies are available in patients with chronic allograft dysfunction. This is the first controlled study to evaluate long-term survival and both renal and cardiac outcomes in nondiabetic RTRs with allograft dysfunction who were converted from CNI to SRL. METHODS: We evaluated 13 RTRs with biopsy-proven allograft dysfunction who underwent early conversion from CNI to SRL, and 26 controls with normal graft function taking CNI. All continued both steroids and mycophenolate mofetil. SRL was titrated to trough levels of 4-8 ng/mL. Outcome measures included 3-year event-free survival, acute rejection rate and 3-year changes in Modification of Diet in Renal Disease (MDRD) Study equation estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMi) as assessed by echocardiography. RESULTS: Compared with controls, patients on SRL showed better 3-year event-free survival (p=0.024; log-rank test), significant eGFR increase (+5.5 ± 8.9 vs, -6.4 ± 14.7 ml/min per 1.73 m2, p=0.011), LVMi regression (-9.0 ± 7.6 g/m(2.7) vs. 1.0 ± 10.1 g/m(2.7), p=0.0038) and similar acute rejection rate. Three-year change in eGFR was the only significant predictor of event-free survival by Cox regression analysis (hazard ratio = 0.96; 95% confidence interval, 0.93-0.99; p=0.017), whereas SRL was the strongest predictor of both eGFR increase (beta coefficient, 0.342; p=0.01) and LVM reduction (beta coefficient, -0.609; p=0.0001) by multivariate regression analysis. CONCLUSIONS: Conversion from CNI to SRL in RTRs with allograft dysfunction proved to be associated with better survival, improved renal graft function and regression of cardiac hypertrophy.

Coronary flow reserve is impaired in hypertensive patients with subclinical renal damage.

BACKGROUND: Renal dysfunction is relatively common in patients with primary hypertension (PH). A reduction in coronary vasodilator capacity has recently been reported in patients with renal damage undergoing coronary angiography. We investigated the relationship between coronary flow reserve (CFR) and early renal abnormalities in patients with PH and normal serum creatinine. METHODS: Seventy-six untreated patients were studied. Albuminuria was measured as the albumin-to-creatinine ratio and glomerular filtration rate (eGFR) was estimated by the Cockroft-Gault formula. Chronic kidney disease (CKD) was defined as an eGFR <60 ml/min/1.73 m(2) and/or in the presence of microalbuminuria. Coronary blood flow velocities (cm/s) were measured by Doppler ultrasound at rest and after adenosine administration. CFR was defined as the ratio of hyperemic-to-resting diastolic peak velocities. RESULTS: Prevalence of reduced eGFR, microalbuminuria, CKD, and left ventricular (LV) hypertrophy was 8, 10, 16, and 31%, respectively. Overall, 10% of patients showed impaired CFR (i.e., <2.0). Patients with CKD were more likely to be older (P < 0.05) and of female gender (P < 0.01) and showed higher LV mass index (LVMI) (P < 0.05), lower CFR (P < 0.05; analysis of covariance, P < 0.05), and CFR/LVMI (P < 0.05) than patients with normal renal function. Conversely, patients with impaired CFR showed a significantly higher prevalence of reduced eGFR (chi(2) 5.2, P < 0.05), microalbuminuria (chi(2) 10.2, P < 0.01), and CKD (chi(2) 9.2.1, P < 0.01). Even after adjustment for gender, the presence of CKD entailed a sevenfold higher risk of having impaired CFR (confidence interval 1.17-40.9, P < 0.05). CONCLUSION: Early renal abnormalities are associated with reduced CFR in PH.

Vascular permeability, blood pressure, and organ damage in primary hypertension.

Sub-clinical organ damage is a strong independent predictor of cardiovascular mortality in primary hypertension, and its changes over time parallel those in risk of cardiovascular events. A better understanding of the pathogenetic mechanisms underlying the development of target organ damage may help us devise more effective therapeutic strategies. We therefore investigated the relationship between the presence of organ damage and some of its potential determinants, such as blood pressure severity and early atherosclerotic abnormalities. Thirty-seven untreated, non-diabetic hypertensive patients were enrolled. Target organ damage was assessed by albuminuria and left ventricular mass index; systemic vascular permeability was evaluated by transcapillary escape rate of albumin (TERalb); and blood pressure was measured by 24h ambulatory blood pressure monitoring. The albumin-to-creatinine ratio and left ventricular mass index were directly related to TERalb (r = 0.48, p = 0.003 and r = 0.39, p < 0.020, respectively) and 24-h systolic blood pressure values (r = 0.54, p < 0.001; r = 0.60, p < 0.001). The simultaneous occurrence of increased blood pressure load and TERalb was associated with higher left ventricular mass index values (p = 0.012) and entailed an increased risk of having at least one sign of damage (chi2 = 17.4; p < 0.001). Logistic regression analysis showed that the risk of presenting at least one sign of organ damage increased more than ten-fold when TERalb was above the median and more than five-fold with each 10 mmHg increase in 24-h systolic blood pressure. Blood pressure load and vascular permeability are potentially modifiable factors that are independently associated with the occurrence of sub-clinical signs of renal and cardiac damage in hypertensive patients.

Global risk stratification in primary hypertension: the role of the kidney.

OBJECTIVE: Microalbuminuria and a reduction in creatinine clearance are well known, independent predictors of unfavourable cardiovascular prognosis. Our aim was to evaluate the impact of renal damage on global risk stratification in 459 non-diabetic, untreated hypertensive patients (64% men, mean age 47.3 years). METHODS: Renal damage was defined as creatinine clearance < 60 ml/min per 1.73 m2 (Cockcroft-Gault formula) or the presence of microalbuminuria (albumin to creatinine ratio). Cardiac and vascular organ damage was assessed by ultrasound scan. We evaluated the impact of renal damage, left ventricular hypertrophy and carotid atherosclerosis on risk stratification as recommended by the 2007 European Society of Hypertension-European Society of Cardiology Guidelines. RESULTS: The prevalence of renal damage, microalbuminuria and creatinine clearance < 60 ml/min per 1.73 m2 was 24, 12 and 13%, respectively. There was no correlation between albuminuria and estimated creatinine clearance, and only 0.9% of patients showed microalbuminuria and reduced creatinine clearance simultaneously. The presence of renal damage entailed a 3.3 times higher risk of having cardiovascular abnormalities. Based on routine work-up, 58% of our study patients were classified as high-very high risk. The simultaneous evaluation of albuminuria and creatinine clearance resulted in a significant change in risk stratification, since 68% of patients were classified in the high-very high risk class. The search for left ventricular hypertrophy or carotid atherosclerosis by ultrasonography did not improve risk stratification significantly as compared to the assessment of renal damage. CONCLUSIONS: Our findings support the assessment of renal abnormalities as the first step when evaluating target organ damage for cardiovascular risk assessment in hypertensive patients.

Inappropriate left ventricular mass is associated with microalbuminuria independently of left ventricular hypertrophy in primary hypertension.

OBJECTIVE: Inappropriate left ventricular mass (LVM) and microalbuminuria predict cardiovascular events in hypertension. We attempted to evaluate the relationship between inappropriate LVM and albuminuria in hypertensive patients. PATIENTS AND METHODS: Four hundred and two nondiabetic, untreated patients with primary hypertension were studied. The appropriateness of LVM to cardiac workload was calculated by the ratio of observed LVM to the predicted value using the reference equation. Albuminuria was evaluated by the urinary albumin to creatinine ratio. RESULTS: The deviation of LVM from the predicted value was positively related to albuminuria (P < 0.0001). Multiple regression analysis showed that albuminuria (0.0182), pulse pressure (P < 0.0001) and left ventricular hypertrophy (LVH) (P < 0.0001) were the only independent predictors of observed/predicted LVM. When subjects were divided into subgroups on the basis of the presence/absence of inappropriate LVM, patients with inappropriate LVM showed higher urinary albumin excretion (P < 0.0001), regardless of potential confounding factors, including LVH (analysis of covariance, P = 0.0453), and higher prevalence of microalbuminuria (P = 0.0024) compared to those without it. Analogous results were obtained by looking at the study patients on the basis of the presence of micro- or normoalbuminuria. Indeed, patients with microalbuminuria showed higher prevalence of inappropriate LVH compared to other left ventricular geometries (appropriate LVH and absence of LVH) (P < 0.0001). After adjusting for confounders, microalbuminuria entailed a three- and five-fold greater risk of having appropriate and inappropriate LVH, respectively. CONCLUSIONS: Inappropriate LVM is associated with albuminuria in hypertension. These data strengthen the role of microalbuminuria as an indicator of high cardiovascular risk.

Mild hyperuricemia and subclinical renal damage in untreated primary hypertension.

BACKGROUND: Subclinical renal damage and hyperuricemia are not uncommon in patients with primary hypertension. Whether mild hyperuricemia reflects a subclinical impairment of renal function or contributes to its development is currently debated. We investigated the relationship between serum uric-acid levels and the occurrence of early signs of kidney damage. METHODS: Four hundred eighteen patients with primary hypertension were studied. Albuminuria was measured as the albumin-to-creatinine ratio, and creatinine clearance was estimated by the formula of Cockcroft and Gault. Interlobar resistive index and renal abnormalities, ie, the renal volume-to-resistive index ratio, were evaluated by renal Doppler and ultrasound. RESULTS: Uric acid was directly related to resistive index (P = .007) in women and to albuminuria (P = .04) in men, and was inversely related to the renal volume-to-resistive index ratio in both men (P = .005) and women (P = .02). Patients with uric-acid levels above the median showed a higher prevalence of microalbuminuria (14% v 7%, P = .012) and of renal abnormalities (41% v 33%, P = .007). Moreover, when creatinine clearance was taken as a covariate, patients with increased uric-acid levels showed higher albuminuria and resistive indices, and a lower renal volume-to-resistive index ratio. Even after adjustment for several risk factors, each standard deviation increase in serum uric acid entailed a 69% higher risk of microalbuminuria, and a 39% greater risk of ultrasound detectable renal abnormalities. CONCLUSIONS: Mild hyperuricemia is associated with early signs of renal damage, ie, microalbuminuria and ultrasound-detectable abnormalities, regardless of the glomerular filtration rate in primary hypertension.

Improving cardiovascular risk stratification: the case for redefining microalbuminuria.

Large epidemiological studies have pointed out that regardless of the degree of hypertension, the cost-effectiveness of antihypertensive treatment increases in parallel with the global burden of risk. Therefore, there has been growing interest in developing sensitive and easy-to-perform ways to accurately and inexpensively identify patients at high cardiovascular risk. Numerous studies over the past years have provided evidence that microalbuminuria is a concomitant of extrarenal signs of hypertensive organ damage, as well as a strong, independent predictor of cardiovascular and cerebrovascular events. Recent clinical data indicate that the risk of cardiovascular morbidity and mortality is linearly related to the degree of urinary albumin excretion, with no identifiable threshold or plateau. Furthermore, it has been demonstrated that a reduction in albuminuria under antihypertensive treatment is paralleled by changes in cardiovascular risk. Therefore, the routine search for microalbuminuria could lead to a significant improvement in the evaluation and treatment of patients with primary hypertension.

Blood pressure load, vascular permeability and target organ damage in primary hypertension.

BACKGROUND: Target organ damage (TOD) is an often reversible subclinical condition that may precede major cardiovascular events in primary hypertensive patients. Furthermore, TOD has been shown to be a complex, multifactorial process which does not depend on blood pressure (BP) reduction alone. We therefore investigated the relationship between BP load, vascular permeability and the occurrence of TOD. PATIENTS AND METHODS: Thirty-seven never-treated, nondiabetic hypertensive patients were enrolled. Albuminuria was measured as the albumin to creatinine ratio (ACR), left ventricular mass index (LVMI) was assessed by echocardiography, systemic vascular permeability was evaluated by transcapillary escape rate of albumin (TERalb), and BP was measured by means of 24-hour ambulatory BP monitoring. RESULTS: Patients with microalbuminuria showed higher levels of body mass index (BMI) (p<0.034), 24-hour systolic BP levels (p<0.001), left ventricular mass index (LVMI) (p=0.003) and capillary permeability to albumin (p<0.005), as compared with normoalbuminurics. Increased BP load and vascular permeability were associated with higher LVMI (p=0.012) and with an increased risk of having microalbuminuria and/or left ventricular hypertrophy (Chi square=17.4; p<0.001). Logistic regression analysis showed that the risk of having at least 1 sign of TOD was 10-fold higher in patients with TERalb above the median, and almost 5-fold higher for each 10 mm Hg increase in systolic blood pressure. CONCLUSIONS: Abnormal vascular permeability and increased BP load are potentially modifiable risk factors that are independently associated with the development of subclinical cardiac and renal damage.

C-reactive protein and target organ damage in untreated patients with primary hypertension.

High sensitivity C-reactive protein (hs-CRP) has been recognized as a risk factor for cardiovascular disease. Asymptomatic organ damage is known to precede cardiovascular events in hypertension. The aim of the present study was to investigate the relationship between hs-CRP and signs of organ damage, namely left ventricular mass index (LVMI), albuminuria, and carotid atherosclerosis in a group of hypertensive patients. One hundred and eighty-two untreated patients with primary hypertension were studied. HS-CRP was measured by immunonephelometry. LVMI was assessed by echocardiography, albuminuria was measured as albumin to creatinine ratio, and carotid atherosclerosis by ultrasonography. Patient stratification according to quartiles of hs-CRP showed a significant trend toward higher age, prevalence of left ventricular hypertrophy, and carotid plaques. Moreover, there was a significant correlation among hs-CRP quartiles and left ventricular mass index, carotid cross-sectional area, carotid plaques, and albuminuria. Multiple regression analysis showed that, after adjusting for established cardiovascular risk factors (ie, age, duration of hypertension, smoking habit, body mass index (BMI), 24-hour systolic and diastolic blood pressures, glucose, creatinine, uric acid, triglycerides, total and low-density lipoprotein cholesterol), hs-CRP remained a strong correlate of target organ damage. These results support the importance of chronic microinflammation in the development of atherosclerotic disease in hypertension.

Microalbuminuria, blood pressure load, and systemic vascular permeability in primary hypertension.

BACKGROUND: 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. METHODS: 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 (125)I-albumin). Twenty-four-hour ambulatory BP, renal hemodynamics, and hormones of the renin-angiotensin-aldosterone system (RAAS) were also assessed. RESULTS: 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. CONCLUSIONS: Microalbuminuria is associated with greater systemic BP load and increased vascular permeability in patients with primary hypertension.