Markers Of Subclinical Organ Damage Research Articles

“Stifflammation” in hypertension is a predictor of future cardiovascular hospitalizations

Abstract Background/Introduction Hypertension is associated with increased cardiovascular risk, inflammation and arterial stiffness. Purpose We sought to investigate the role of inflammation and arterial stiffness in the prognosis of cardiovascular hospitalizations in hypertensive patients over an extended follow-up. Methods One hundred and seventy-three patients (mean age 52.5±13.2 years, 57% males) untreated hypertensives at baseline without cardiovascular disease, were included in the study. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). High-sensitivity C-reactive protein (hsCRP) was measured in venous blood samples. Other markers of subclinical organ damage [left ventricular mass index (LVMI) by echocardiography and estimated glomerular filtration rate (eGFR)] were also evaluated in all patients. Results During 13.6±0.4 years of follow-up, forty-four patients (25.4%) patients were admitted in hospital due to cardiovascular causes. In multivariable logistic regression analysis, only higher hsCRP (Odds Ratio [OR] = 3.34, 95% Confidence intervals [CI]: 1.22–9.51, P=0.02) and increased PWV (OR = 1.48, 95% Confidence intervals [CI]: 1.03–2.12, P=0.036) were associated with higher risk of cardiovascular hospitalizations, which was independent of age, gender, systolic blood pressure, LVMI and presence of diabetes. In further analysis, receiver operating characteristic (ROC) curves were generated to evaluate the ability of hsCRP and PWV to discriminate subjects with cardiovascular hospitalization. The area under the curve (AUC) and 95% CIs of the ROC curves were AUC=0.69 (95% CI: 0.59–0.78, p<0.001) for hsCRP and AUC=0.74 (95% CI: 0.65–0.83, P<0.001) for PWV (Figure). Conclusions Our study shows the independent complimentary prognostic role of inflammation and arterial stiffness in the prognosis of hypertensives even in studies with extended follow-up. Funding Acknowledgement Type of funding sources: None. ROC curves for the prediction of outcome

Aortic stiffness and incident diabetes: the hard, bittersweet truth

Abstract Background/Introduction Aortic stiffness increases with advancing age and is a major risk factor for age-related morbidity and mortality. Aortic stiffness and glycaemic dysregulation are related; however, temporal relationships between aortic stiffness and incidence of diabetes have not been fully delineated. Purpose We sought to investigate the role of arterial stiffness in the prediction of incident diabetes. Methods 376 untreated hypertensive patients (mean age 52.6±12.5 years, 201 males) without known cardiovascular disease and without known history of diabetes, were included in the study. Markers of subclinical organ damage [carotid-femoral pulse wave velocity (PWV) and estimated glomerular filtration rate (eGFR)] were evaluated in all patients. eGFR was estimated using the Cockcroft-Gault formula. Hemoglobin A1c (HbA1c) and blood glucose were measured in venous blood samples. Patients were prospectively followed-up, for incidence of diabetes as defined by the American Diabetes Association criteria. Results During a median 13.5 years follow-up, forty-six patients (12.2%) patients were diagnosed with diabetes. In multivariable logistic regression analysis, only higher PWV (Odds Ratio [OR] = 1.271, 95% Confidence intervals [CI]: 1.002–1.612, P=0.048) was associated with higher risk of incident diabetes, which was independent of age, sex, pulse pressure, HbA1c, fasting blood glucose and eGFR. In further analysis, receiver operating characteristic (ROC) curves were generated to evaluate the ability of PWV to discriminate subjects with diabetes. The area under the curve (AUC) and 95% CIs of the ROC curve was AUC=0.66 (95% CI: 0.58–0.74, P=0.001) for PWV (Figure 1). Conclusions In our cohort, higher aortic stiffness was associated with higher risk of incident diabetes. Figure 1. ROC curve for the prediction of diabetes Funding Acknowledgement Type of funding source: None

Vascular endothelial growth factor as a potential marker of subclinical organ damage mediated by arterial hypertension

The authors’ report presents a brief review of the key studies, providing the reason for the use of vascular endothelial growth factor as a marker for stratification of the risk of cardiovascular complications in patients with essential hypertension.

THE INTERPLAY BETWEEN INFLAMMATION AND ARTERIAL STIFFNESS IN THE PROGNOSIS OF CARDIOVASCULAR HOSPITALIZATIONS IN HYPERTENSIVES

Objective: Hypertension is associated with increased cardiovascular risk and inflammation as well arterial stiffness have been identified as possible underlying mechanisms. We sought to investigate the role of inflammation and arterial stiffness in the prognosis of cardiovascular hospitalization in hypertensives patients over an extensive follow-up. Design and method: One hundred and seventy-three patients (mean age 52.5 ± 13.2 years, 57% males) untreated hypertensives were included in the study. Markers of subclinical organ damage [left ventricular mass index (LVMI), carotid-femoral pulse wave velocity (PWV) and estimated glomerular filtration rate (eGFR)] were evaluated in all patients. LVMI was assessed echocardiographically using the Devereux formula. eGFR was estimated using the MDRD formula. High-sensitivity C-reactive protein (hsCRP) was measured in venous blood samples. Results: During 13.6 ± 0.4 years of follow-up, forty-four patients (25.4%) patients were admitted in hospital due to cardiovascular causes (4 of them died). Hypertensives that were admitted were older (58 vs. 51 years, p = 0.001) compared to hypertensives with no hospitalization. In multivariable logistic regression analysis, only higher hsCRP (Odds Ratio [OR] = 3.34, 95% Confidence intervals [CI]: 1.22–9.51, P = 0.020) and increased PWV (OR = 1.48, 95% Confidence intervals [CI]: 1.03–2.12, P = 0.036) were associated with higher risk of cardiovascular hospitalizations, which was independent of age, gender, systolic blood pressure, left ventricular mass index and presence of diabetes. In further analysis, receiver operating characteristic (ROC) curves were generated to evaluate the ability of hsCRP and PWV to discriminate subjects with cardiovascular hospitalization. The area under the curve (AUC) and 95% CIs of the ROC curves were AUC = 0.69 (95% CI: 0.59–0.78, p < 0.001) for hsCRP and AUC = 0.74 (95% CI: 0.65–0.83, P < 0.001) for PWV (Figure). Conclusions: Our study shows the independent complimentary prognostic role of inflammation and arterial stiffness in the prognosis of hypertensives even in studies with extensive follow-up.

Sexual dysfunction as a determinant of cardiovascular outcome in patients undergoing chronic hemodialysis.

Sexual dysfunction (SD) is common in men and women with chronic kidney disease (CKD) and is considered as an early marker for cardiovascular (CV) disease. We hypothesized that patients with SD have higher risk for vascular damage of the large arteries, accelerated vascular aging, and consequently higher CV mortality than other end-stage renal disease (ESRD) patients. In this study, the International Index of Erectile Function (IIEF) questionnaire and the Female Sexual Function Index (FSFI) questionnaire were applied in men and women, respectively. Ambulatory blood pressure monitoring (ABPM), arterial stiffness, and ankle-brachial index (ABI) were performed in all patients. Pulse wave velocity (PWV) was significantly slower in non-SD patients (10.5 vs. 8.8 m/s; p < 0.001) with significantly lower number of non-SD patients with PWV > 10 m/s compared to SD patients (p < 0.001). Only 57% of the patients with prior CV event had PWV > 10 m/s. No difference in AIx was observed. Non-SD patients had better values of ABI (0.83 vs. 1.09; p < 0.05) with significantly lower number of non-SD patients with ABI < 0.9 compared to SD patients (p = 0.001) as well as smaller percentage of LVH (57.5% vs. 80.7%; p = 0.01). There were no differences in hemodynamic parameters when patients with SD were divided by sex. Pulse wave velocity was the strongest predictor of lower IIEF and FSFI scores. Mean survival time was longer in non-SD patients than in SD patients (11.6 vs. 10.5 months, p = 0.019). The higher incidence of prior CV events and CV mortality found in SD patients on hemodialysis (HD) is a consequence of accelerated vascular aging. Sexual dysfunction in HD patients should also be considered a marker of subclinical organ damage and future CV events. Our study confirms the predictive role of PWV in HD patients.

Inverse association between type 2 diabetes and aortic root dimension in hypertensive patients

BackgroundSome data support the concept that aortic root diameter (ARD) in hypertension may be regarded as a marker of subclinical organ damage. The impact of type 2 diabetes mellitus (DM) on cardiac structure and function is known, although the relationship between DM and ARD is not clear. The aim of our study was to evaluate the influence of DM on ARD in hypertensive patients. MethodsWe enrolled 1693 hypertensive patients (aged 63.7±9.6years). The population was divided into two groups: the first one with DM (n=747) and the second one without DM (n=946). ARD was measured by echocardiography at level of Valsalva's sinuses using echocardiography M-mode tracings. It was considered as absolute measure and normalized to height (ARD/H) and body surface area (ARD/BSA).Left ventricular mass index (LVMI) and some parameters of systolic and diastolic function have been valued by means of echocardiography and tissue Doppler imaging. ResultsThe DM group was characterized by more elevated values of LVMI and a worst systolic and diastolic function. ARD value was significantly lower in DM group in comparison to patients without DM only when indexed for BSA (ARD/BSA=18.7±2.3mm/m2 vs 18.3±2.0mm/m2, p=0.01). This difference remained statistically significant, even after correction by age, sex and BMI (p=0.01).A multivariate linear regression analysis demonstrated an inverse relationship between DM and ARD/BSA after correction for potential confounders (β=0.10, p<0.001). ConclusionsOur results confirm the hypothesis of a protective role of DM on aortic root dilatation.

Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration.

OBJECTIVECarotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.RESEARCH DESIGN AND METHODSIn a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33–92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.RESULTSAverage mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12–1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between −0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91–1.08).CONCLUSIONSDespite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

Metabolomic signature of arterial stiffness in male patients with peripheral arterial disease.

Arterial stiffness is an independent determinant of cardiovascular risk and a marker of subclinical organ damage. Metabolomics may facilitate identification of novel low-molecular cardiovascular risk factors. The aim of the present study was to compare metabolic signatures and functional-biochemical characteristics of patients with peripheral arterial disease (PAD) and clinically healthy subjects. We studied 42 men with symptomatic PAD (aged 66±7 years) and 46 healthy men (aged 66±8 years). Aortic pulse wave velocity (aPWV) was assessed by applanation tonometry using the Sphygmocor device. Metabolic profiling was performed with high-performance liquid chromatography and mass spectrometry. Serum oxidized low-density lipoprotein (oxLDL) level was measured by enzyme-linked immunosorbent assay. The aPWV as well as serum levels of lactate, free carnitine and 11 amino acids including tyrosine were higher among the patients with PAD. In contrast, serum levels of pyruvate, citrate, α-ketoglutarate, aconitate and cysteine were higher in the control group. In multiple regression models, aPWV was independently determined by log-tyrosine and log-oxLDL in the patients (R(2)=0.61; P<0.001) and by age, log-pyruvate and log-oxLDL in the controls (R(2)=0.52; P<0.001). Our study describes for the first time significant differences in metabolomic signature of patients with advanced atherosclerosis compared with clinically healthy controls. The aPWV is independently associated with serum levels of tyrosine and oxLDL in the patients with PAD and is related to pyruvate and oxLDL levels in the control group. The measurement of low-molecular metabolites, which are related to changes in vascular phenotypes, may lead to identification of novel vascular risk markers.

Albuminuria is Associated With Subendocardial Viability Ratio in Chronic Kidney Disease Patients

Background/Aims: Albuminuria is a well-established marker of subclinical organ damage. Pulse-wave analysis (PWA) employs the technique of applanation tonometry to obtain a peripheral pulse pressure waveform, from which central hemodynamic data are derived by application of the transfer function. Using PWA we can measure the subendocardial viability ratio (SEVR) and ejection duration (ED). SEVR or the Buckberg index is a non-invasive estimate of myocardial workload, oxygen supply and perfusion and a measure of the ability of the arterial system to meet the heart`s energy requirements. ED is the duration of ventricular ejection. The objective of this study was to evaluate the relationship between albuminuria and PWA parameters in chronic kidney disease (CKD) patients. Methods: We studied 86 CKD patients aged 59.8±13.5 years, 56 (65.1%) were male. PWA analysis and 24-hour ambulatory blood pressure (24hABP) monitoring were performed. The following parameters were calculated: (1) aortic augmentation index with and without correction for a heart rate of 75 (Aix and AIx@ HR75), (2) SEVR, calculated as the ratio of the diastolic pressure time index and the systolic pressure time index, (3) ED, (4) estimated central aortic systolic and diastolic pressure and (5) central aortic pulse pressure calculated as the difference between estimated aortic systolic and diastolic BP. Blood samples and urine albumin-to-creatinine ratio (UACR) were analyzed; UACR values were natural log transformed (lnUACR). Results: Using CKD-EPI creatinine-cystatin C formula the eGFR in patients was 7-130 ml/min/1.73m² (mean 32.6; SD±24.6). We found statistically significant correlation between lnUACR and cystatin C (r=0.308; P=0.004), eGFR (r=-0.219; P=0.04), hemoglobin (r=-0.255; P=0.02), phosphorus (r=0.222; P=0.04), iPTH (r=0.268; P=0.01), SEVR (r=-0.254; P=0.02) and ED (r=0.315; P=0.003). No statistically significant correlations between lnUACR and cardiac biomarkers TnI, NT-proBNP, central aortic BP and 24h ABP values were found. Using multiple regression analysis statistically significant association was found between SEVR as dependent variable and lnUACR (β=-0.223, P=0.039), sex (β=-0.216, P=0.035), and diabetes (β=0.332, P=0.001). Multiple regression analysis with ED as dependent variable has shown statistically significant association with lnUACR (β=0.242, P=0.031) and diabetes (β=-0.275, P=0.01). Patients were stratified into tertiles according to the lnUACR. Statistically significant differences in serum creatinine (P=0.001), cystatin C (P=0.012), hemoglobin (P=0.03), calcium (P=0.036), iPTH (P=0.008), SEVR (P=0.007) and ED (P=0.004) were found between tertiles. In post hoc analysis we found statistically significant differences between first and third tertile in SEVR (P=0.002; 95% CI:10.5-45) and in ED (P=0.001; 95% CI:-6.89-(-1.87)). Conclusions: Nondialysis CKD patients with higher levels of albuminuria have lower SEVR and higher ED and our results have shown the importance of central hemodynamic parameters like are SEVR and ED as a better or earlier noninvasive hemodynamic indexes in these patients.

Renal haemodynamics and severity of carotid atherosclerosis in hypertensive patients with and without impaired renal function

Background and aimRenal resistance index (RRI), assessed by Duplex-Doppler sonography, has been classically considered as a mere expression of intrarenal vascular resistance. Recent studies, however, have showed that RRI is also influenced by upstream factors, especially arterial compliance, confirming its possible role as a marker of systemic vascular alterations.Several studies have shown that carotid intima-media thickness (cIMT) and carotid plaques (cP), assessed by ultrasonography, are documented markers of subclinical organ damage as well as expression of progressive atherosclerotic disease, and that they get worse with the progressive deterioration of renal function.The study was aimed to evaluate the relationship between RRI and severity of carotid atherosclerosis in hypertensive subjects with and without impaired renal function. Methods and resultsThe study population, including 263 hypertensive patients (30–70 years), was split into 3 groups based on cIMT and presence of cP (cIMT ≤ 0.9 mm and no cP; cIMT > 0.9 mm and no cP; cP). All patients were also divided into 2 subgroups (normal renal function; CKD stage I–IV).A stepwise increase in RRI corresponding to the groups of progressive severity of carotid atherosclerosis was observed (respectively 0.61 ± 0.07, 0.65 ± 0.06, 0.68 ± 0.06; p < 0.001). A strong positive correlation was observed between RRI and cIMT in the whole population (r = 0.43; p < 0.001) and in the subgroups with (r = 0.42; p < 0.001) and without (r = 0.39; p < 0.001) CKD. These associations remained statistically significant even after adjustment for various confounding factors. ConclusionShowing a close association between RRI and severity of carotid atherosclerosis, our results strengthen the concept that RRI is a marker of systemic vascular changes.

Abdominal obesity and low-grade systemic inflammation as markers of subclinical organ damage in type 2 diabetes

AimThis study aimed to explore the associations between abdominal obesity, inflammatory markers and subclinical organ damage in 740 middle-aged patients with type 2 diabetes. MethodsWaist circumference (WC) and sagittal abdominal diameter (SAD) were measured, and blood samples were analyzed for C-reactive protein (CRP) and IL-6. Carotid intima–media thickness (IMT) was evaluated by ultrasonography, and aortic pulse wave velocity (PWV) measured with applanation tonometry. ResultsAbdominal obesity as determined by SAD and WC was significantly correlated with IL-6 (WC: r=0.27, P<0.001; SAD: r=031, P<0.001), CRP (WC: r=0.29, P<0.001; SAD: r=0.29, P<0.001), IMT (WC: r=0.09, P=0.013; SAD: r=0.11, P=0.003) and PWV (WC: r=0.18, P<0.001; SAD: r=0.21, P<0.001). In multiple linear regressions with IMT and PWV as dependent variables, and age, gender, statin use, systolic blood pressure (SBP), body mass index (BMI), CRP and HbA1c as independent variables, both SAD and WC remained associated with IMT and PWV. On stepwise linear regression and entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV. ConclusionBoth SAD and WC are feasible measures of obesity, and both provide information on inflammation, atherosclerosis and arterial stiffness in type 2 diabetes, while SAD appears to be slightly more robustly associated with subclinical organ damage than WC.

Detection of left ventricular hypertrophy in obesity

Detection of left ventricular hypertrophy in obesity

Can ambulatory blood pressure measurements substitute assessment of subclinical cardiovascular damage?

We have previously demonstrated that markers of subclinical organ damage (SOD) improve cardiovascular risk prediction in healthy individuals. We wanted to investigate whether this additive effect of SOD was due to inaccurate blood pressure (BP) measurement or whether ambulatory BP (AMBP) added further to risk prediction. In a population cohort of 1385 Danish individuals free of cardiovascular disease and diabetes, we recorded traditional risk factors, AMBP and pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular mass index (LVMI) and carotid atherosclerotic plaques at baseline. A composite cardiovascular endpoint (CEP) consisting of cardiovascular death and nonfatal myocardial infarction and stroke was recorded in national registries. During a median follow-up of 12.8 years, a total of 119 CEPs occurred. In categorical analysis, presence of SOD as well as masked hypertension increased sensitivity of Systemic Coronary Risk Estimation from 73.9 to 89.1% (P < 0.001) and reduced specificity from 60.1 to 41.8% (P < 0.001). In continuous analysis, logUACR [hazard ratio = 1.20 (95% confidence interval [CI] 1.05-1.38), P = 0.009], atherosclerotic plaques [hazard ratio = 1.82 (95% CI 1.21-2.74), P = 0.004] and 24-h SBP [hazard ratio = 1.34 (95% CI 1.12-1.60), P = 0.002] but not logPWV or LVMI predicted CEP in a model with adjustments for age, sex, conventional BP, total cholesterol and smoking. Compared with a risk model using only traditional risk factors, adding PWV, UACR, plaques, LVMI and 24-h SBP increased C-index significantly from 0.76 to 0.79% and produced a net reclassification improvement of 23.3% (P = 0.001). UACR and plaques predicted cardiovascular events independently of AMBP and improved risk prediction.

Insulin resistance and coronary flow velocity reserve in patients with autosomal dominant polycystic kidney disease

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to investigate coronary flow velocity reserve (CFVR) as a marker of endothelial dysfunction, carotid intima media thickness (CIMT) as a marker of subclinical organ damage and insulin resistance (IR) as a cardiovascular risk factor in patients with ADPKD. Twenty-two normotensive ADPKD patients with well-preserved renal function and 19 healthy subjects were included in the study. Creatinine clearances were calculated by the Cockcroft-Gault formula. The homeostasis model of IR (HOMA-IR) was used to measure IR. CIMT was measured by high-resolution vascular ultrasound. CFVR was calculated as the ratio of hyperaemic to baseline diastolic peak velocities by echocardiography. There was no significant difference between the two groups regarding age, gender, body mass index, systolic and diastolic blood pressures, cholesterol and triglyceride levels. However, CIMT and HOMA-IR were significantly increased and CFVR was significantly decreased in patients with ADPKD compared with healthy subjects. The findings of decreased CFVR, increased CIMT and increased IR suggest that cardiovascular risk is elevated even in the early stages of ADPKD.

Risk stratification in cardiovascular disease primary prevention – scoring systems, novel markers, and imaging techniques

The aim of this paper is to review and discuss current methods of risk stratification for cardiovascular disease (CVD) prevention, emerging biomarkers, and imaging techniques, and their relative merits and limitations. This report is based on discussions that took place among experts in the area during a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy in September 2009. Classical risk factors such as blood pressure and low-density lipoprotein cholesterol levels remain the cornerstone of risk estimation in primary prevention but their use as a guide to management is limited by several factors: (i) thresholds for drug treatment vary with the available evidence for cost-effectiveness and benefit-to-risk ratios; (ii) assessment may be imprecise; (iii) residual risk may remain, even with effective control of dyslipidemia and hypertension. Novel measures include C-reactive protein, lipoprotein-associated phospholipase A(2) , genetic markers, and markers of subclinical organ damage, for which there are varying levels of evidence. High-resolution ultrasound and magnetic resonance imaging to assess carotid atherosclerotic lesions have potential but require further validation, standardization, and proof of clinical usefulness in the general population. In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk-guided therapy in CVD prevention.

Creatinine clearance and subclinical target organ damage in primary hypertension

Introduction: Despite the widely recognized dangers of uncontrolled hypertension, the disease remains inadequately treated in the majority of patients. This may be, in large part, because of the asymptomatic nature of the disease for the first 15 to 20 years, even as it progressively damages the cardiovascular system. Therefore, assessment of hypertension related subclinical target-organ damage represents a key diagnostic procedure for the risk stratification of hypertensive patients. Methods: A prospective case control study of 40 cases (hypertensive patients with CCR&lt;60) and 40 controls (hypertensive patients with CCR&gt;60) was conducted in Tribhuvan University Teaching Hospital (TUTH). Renal function was estimated by the Cockcroft-Gault formula. Left ventricular hypertrophy was determined by echocardiography. Retinal vascular changes were evaluated by direct ophthalmoscopy. Microalbumin in urine was measured from spot morning sample. Results: The prevalence of Left ventricular hypertrophy (LVH), microalbuminuria and retinopathy in cases and control group was 55% VS 20% (P=.001), 50% VS 20% (P=.004) and 92.5% VS 52.5% (P=.001). Patients with microalbuminuria showed prevalence of LVH, CCR&lt;60 and retinopathy as 78.57%, 71.43% and 100% respectively. There was high prevalence of grade I and grade II retinopathy in patients with low CCR Conclusions: Results show that a reduction in creatinine clearance and/or presence of microalbuminuria is a marker of subclinical organ damage in patients with primary hypertension and normal serum creatinine irrespective of BP load and other traditional risk factors. Keywords: Creatinine clearance; primary hypertension; subclinical; target organ damage. DOI: http://dx.doi.org/10.3126/joim.v32i3.4957 Journal of Institute of Medicine, December, 2010; 32:3 30-33

Soluble urokinase plasminogen activator receptor is associated with subclinical organ damage and cardiovascular events

ObjectiveThe soluble urokinase plasminogen activator receptor (suPAR) is a plasma marker of low grade inflammation and has been associated with cardiovascular risk. We wanted to investigate whether suPAR was associated with markers of subclinical organ damage. MethodsIn a population sample of 2038 individuals, aged 41, 51, 61 and 71 years, without diabetes, prior stroke or myocardial infarction, not receiving any cardiovascular, anti-diabetic or lipid-lowering medications, we measured urine albumin/creatinine ratio (UACR), carotid atherosclerotic plaques and carotid/femoral pulse wave-velocity (PWV) together with traditional cardiovascular risk factors and high sensitivity C-reactive protein (hsCRP). ResultssuPAR was significantly associated with the presence of plaques (P=0.003) and UACR (P<0.001), but not PWV (P=0.17) when adjusting for age, gender, systolic blood pressure, cholesterol, plasma glucose, waist/hip ratio, smoking and hsCRP. However, suPAR explained only a small part of the variation in the markers of subclinical organ damage (R2 0.02–0.04). During a median follow-up of 12.7 years (5th–95th percentile 5.1–13.4years) a total of 174 composite endpoints (CEP) of cardiovascular death, non-fatal myocardial infarction and stroke occurred. suPAR was associated with CEP independent of plaques, PWV, UACR, and hsCRP as well as age, gender, systolic blood pressure, cholesterol, plasma glucose, waist/hip ratio and smoking with a standardized hazard ratio of 1.16 (95% confidence interval 1.04–1.28, P=0.006). ConclusionsuPAR was associated with subclinical organ damage, but predicted cardiovascular events independent of subclinical organ damage, traditional risk factors and hsCRP. Further studies must investigate whether suPAR plays an independent role in the pathogenesis of cardiovascular disease.

Urinary Albumin Excretion Is Associated With Nocturnal Systolic Blood Pressure in Resistant Hypertensives

Microalbuminuria is a known marker of subclinical organ damage. Its prevalence is higher in patients with resistant hypertension than in subjects with blood pressure at goal. On the other hand, some patients with apparently well-controlled hypertension still have microalbuminuria. The current study aimed to determine the relationship between microalbuminuria and both office and 24-hour ambulatory blood pressure. A cohort of 356 patients (mean age 64 ± 11 years; 40.2% females) with resistant hypertension (blood pressure ≥ 140 and/or 90 mm Hg despite treatment with ≥ 3 drugs, diuretic included) were selected from Spanish hypertension units. Patients with estimated glomerular filtration rate <30 mL/min/1.73 m(2) were excluded. All patients underwent clinical and demographic evaluation, complete laboratory analyses, and good technical-quality 24-hour ambulatory blood pressure monitoring. Urinary albumin/creatinine ratio was averaged from 3 first-morning void urine samples. Microalbuminuria (urinary albumin/creatinine ratio ≥ 2.5 mg/mmol in males or ≥ 3.5 mg/mmol in females) was detected in 46.6%, and impaired renal function (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) was detected in 26.8%. Bivariate analyses showed significant associations of microalbuminuria with older age, reduced estimated glomerular filtration rate, increased nighttime systolic blood pressure, and elevated daytime, nighttime, and 24-hour diastolic blood pressure. In a logistic regression analysis, after age and sex adjustment, elevated nighttime systolic blood pressure (multivariate odds ratio, 1.014 [95% CI, 1.001 to 1.026]; P=0.029) and reduced estimated glomerular filtration rate (multivariate odds ratio, 2.79 [95% CI, 1.57 to 4.96]; P=0.0005) were independently associated with the presence of microalbuminuria. We conclude that microalbuminuria is better associated with increased nighttime systolic blood pressure than with any other office and 24-hour ambulatory blood pressure monitoring parameters.

Ambulatory arterial stiffness index: a marker of subclinical organ damage in treated and untreated dipper hypertensive patients

Ambulatory arterial stiffness index: a marker of subclinical organ damage in treated and untreated dipper hypertensive patients

Media-to-lumen ratio as predictor of renal abnormalities in hypertension: new findings, new questions

Media-to-lumen ratio as predictor of renal abnormalities in hypertension: new findings, new questions