Novella Conti

Increased Ambulatory Arterial Stiffness Index Is Associated With Target Organ Damage in Primary Hypertension

Increased arterial stiffness has been shown to predict cardiovascular mortality in patients with primary hypertension. Asymptomatic organ damage is known to precede cardiovascular events. We investigated the relationship between a recently proposed index of stiffness derived from ambulatory blood pressure (BP) and target organ damage in 188 untreated patients with primary hypertension. Ambulatory arterial stiffness index was defined as 1 minus the regression slope of diastolic over systolic BP readings obtained from 24-hour recordings. Albuminuria was measured as the albumin:creatinine ratio, left ventricular mass index was assessed by echocardiography, and carotid abnormalities were evaluated by ultrasonography. The prevalence of microalbuminuria, left ventricular hypertrophy (LVH), and carotid abnormalities was 12%, 38%, and 19%, respectively. Ambulatory arterial stiffness index was positively related to age, triglycerides, office and 24-hour systolic BP, 24-hour pulse pressure, urinary albumin excretion, and carotid intima-media thickness. Patients with microalbuminuria, carotid abnormalities, or LVH showed higher ambulatory arterial stiffness index as compared with those without it. After adjusting for confounding factors, each SD increase in ambulatory arterial stiffness index entails an ≈2 times higher risk of microalbuminuria, carotid abnormalities, and LVH and doubles the risk of the occurrence of ≥1 sign of organ damage. Ambulatory arterial stiffness index is associated with organ damage in patients with primary hypertension. These data strengthen the role of this index as a marker of risk and help to explain the high cardiovascular mortality reported in patients with high ambulatory arterial stiffness index.

Ambulatory arterial stiffness index and renal abnormalities in primary hypertension

Objective Arterial stiffness is a predictor of cardiovascular mortality in the general population as well as in hypertension and end-stage renal disease. We investigated the relationship between a recently proposed ambulatory blood pressure monitoring-derived index of arterial stiffness and early signs of renal damage in patients with primary hypertension. Design and setting A total of 168 untreated patients with sustained primary hypertension were studied. Ambulatory arterial stiffness index (AASI) was calculated based on 24-h ambulatory blood pressure readings. Albuminuria was measured as the albumin to creatinine ratio. Creatinine clearance was estimated using the Cockcroft–Gault formula, and the interlobar resistive index was evaluated by renal ultrasound and Doppler examination. Results AASI was positively related to urinary albumin excretion and resistive index, and was negatively related to estimated creatinine clearance and renal volume to the resistive index ratio. Patients with AASI above the median (i.e. > 0.51) showed a higher prevalence of microalbuminuria and a mild reduction in creatinine clearance. Moreover, patients with microalbuminuria or a mild reduction in creatinine clearance had significantly higher AASI values compared with those without, and the greater the renal involvement, the greater the AASI. After adjusting for several potentially confounding variables, we found that each standard deviation increase in AASI (i.e. 0.16) entails an almost twofold greater risk of renal involvement. Conclusion Increased AASI is independently associated with early signs of renal damage in patients with sustained primary hypertension. These results strengthen the usefulness of AASI and ambulatory blood pressure monitoring in cardiovascular risk assessment.

Microalbuminuria Is a Predictor of Chronic Renal Insufficiency in Patients without Diabetes and with Hypertension: The MAGIC Study

BACKGROUND AND OBJECTIVES Increased urinary albumin excretion is a known risk factor for cardiovascular events and clinical nephropathy in patients with diabetes. Whether microalbuminuria predicts long-term development of chronic renal insufficiency (CRI) in patients without diabetes and with primary hypertension remains to be documented. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted an 11.8-year follow-up of 917 patients who did not have diabetes and had hypertension and were enrolled in the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) cohort between 1993 and 1997. Urinary albumin-to-creatinine ratio (ACR) was assessed at baseline in untreated patients in a core laboratory. Microalbuminuria was defined as ACR > or =22 mg/g in men and ACR > or =31 mg/g in women. RESULTS A total of 10,268 person-years of follow-up revealed that baseline microalbuminuria was associated with an increased risk for developing CRI (relative risk [RR] 7.61; 95% confidence interval [CI] 3.19 to 8.16; P < 0.0001), cardiovascular events (composite of fatal and nonfatal cardiac and cerebrovascular events; RR 2.11; 95% CI 1.08 to 4.13; P < 0.028), and cardiorenal events (composite of former end points; RR 3.21; 95% CI 1.86 to 5.53; P < 0.0001). Microalbuminuria remained significantly related to CRI (RR 12.75; 95% CI 3.62 to 44.92; P < 0.0001) and cardiorenal events (RR 2.58; 95% CI 1.32 to 5.05; P = 0.0056) even after adjustment for several baseline covariates. CONCLUSIONS Microalbuminuria is an independent predictor of renal and cardiovascular complications in patients without diabetes and with primary hypertension.

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.

Combined effect of albuminuria and estimated glomerular filtration rate on cardiovascular events and all-cause mortality in uncomplicated hypertensive patients.

Objectives Decreased glomerular filtration rate (GFR) and microalbuminuria predict cardiovascular events and mortality in the general population and in high-risk patients. Their combined prognostic power in low-risk patients has never been reported. We assessed the prognostic role of GFR and albuminuria for cardiovascular disease and all-cause mortality in nondiabetic patients with primary hypertension. Methods We conducted an 11.2-year follow-up of 837 uncomplicated hypertensive patients enrolled in the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) cohort between 1993 and 1997. Urinary albumin-to-creatinine ratio (ACR) and estimated GFR (eGFR) were assessed in untreated patients at baseline. Renal dysfunction was defined as the inclusion in the most unfavorable sex-specific decile of eGFR or of ACR. The primary endpoints were the occurrence of fatal and nonfatal cerebrovascular and cardiac events (CVEs), composite of nonfatal cerebrovascular and cardiac events (CVD) and all-cause death (CEP), and composite of CVD and chronic renal insufficiency (CRE). Results During 9374 person-years of follow-up, the incidence rate for CVE, CRE, and all-cause mortality was 6.3, 7.8, and 3.1 /1000 person-years, respectively. Renal dysfunction was associated with increased risk for CVE [relative risk (RR) 2.13, 95% confidence interval (CI) 1.15–3.93, P = 0.011], CEP (RR 1.78, 95% CI 1.02–3.08, P = 0.027), and CRE (RR 2.47, 95% CI 1.45–4.29, P < 0.001), even after adjusting for several baseline covariates such as sex, duration and severity of blood pressure, and total cholesterol. Conclusion Renal dysfunction is a risk factor for cardiorenal events and all-cause mortality, regardless of traditional confounders, in uncomplicated patients with primary hypertension.

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.

Evaluation of Subclinical Organ Damage for Risk Assessment and Treatment in the Hypertensive Patient: Role of Microalbuminuria

Microalbuminuria, i.e., abnormal urinary excretion of albumin, which is detectable by low cost and widely available tests, is a first-line tool for identifying hypertensive patients who are at higher cardiovascular (CV) risk. Numerous studies have provided evidence that microalbuminuria is a concomitant of cardiac and vascular damage as well as a strong, independent predictor of CV events. An important, emerging issue is that the risk for CV morbidity and mortality is linearly related to urinary albumin excretion and persists well below the currently used cutoff for defining microalbuminuria. Furthermore, late-breaking evidence suggests that a reduction of albuminuria under antihypertensive treatment is paralleled by changes in CV risk. The routine search for target organ damage by means of microalbuminuria could lead to a significant improvement in the evaluation and treatment of patients with primary hypertension.

Renal and cardiac abnormalities in primary hypertension.

Objective The relationship between mild reduction in renal function and cardiac structure and function have not yet been fully elucidated. We investigated cardiac and renal abnormalities in 400 untreated, nondiabetic patients (65% men, mean age 47 years) with primary hypertension and normal serum creatinine. Methods Renal abnormalities were defined as creatinine clearance less than 75 ml/min per 1.73 m2 (Cockcroft–Gault formula) and/or the presence of microalbuminuria (albumin-to-creatinine ratio). Left ventricular structure and function were assessed by echocardiography. Results The prevalence of microalbuminuria and reduced creatinine clearance was 13 and 31%, respectively. Patients with renal abnormalities shared greater left ventricular mass index, higher prevalence of left ventricular hypertrophy, and unfavorable geometric patterns. Microalbuminuria was also associated with inappropriate left ventricular mass and depressed midwall fractional shortening, whereas reduced creatinine clearance was associated with lower stroke volume and higher central pulse pressure/stroke volume ratio and total peripheral resistance. Stepwise regression analysis showed that both albuminuria and creatinine clearance were independently related to left ventricular mass. Logistic regression analysis of the reciprocal interaction of microalbuminuria and reduced creatinine clearance on the occurrence of subclinical cardiac damage showed that reduced creatinine clearance entailed a greater risk of left ventricular hypertrophy in patients with normal albuminuria alone, whereas the presence of microalbuminuria was associated with a greater risk of left ventricular hypertrophy independently of creatinine clearance. Conclusions These findings provide further proof of the role of cardiorenal interaction in the development of hypertension-related cardiovascular disease, and may have clinical implications.

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.

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 24-h 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 (χ2=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.