Giovanni Cerasola

Influence of metabolic syndrome on hypertension‐related target organ damage

Objectives.  The aim of our study was to analyse, in a wide group of essential hypertensive patients without diabetes mellitus, the influence of metabolic syndrome (MS) (defined according to the criteria laid down in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) on markers of preclinical cardiac, renal and retinal damage.

Microalbuminuria, renal dysfunction and cardiovascular complication in essential hypertension

Objective To evaluate the prevalence of microalbuminuria (albumin excretion rate, AER) in a wide hypertensive population, and to evaluate any relationship with cardiovascular damage and renal dysfunction Design A transversal study Subjects and methods In 383 hospitalized Caucasian essential hypertensives (198 men, 185 women) of mean age 44 ±0.5 years and mean clinic blood pressure 170.3 ±0.95/ 103.4 ±0.47 mmHg, metabolic parameters, serum creatinine level (Cs), creatinine clearance rate (CCR), 24 AER and plasma renin activity (PRA) were measured. Furthermore, each patient underwent 24 h ambulatory blood pressure monitoring (ABPM) and echocardiography to measure left ventricular mass, which was indexed both by body surface area to obtain left ventricular mass index (LVMI) and by height to obtain the left ventricular mass indexed for height (LVMH). By Doppler echocardiography, the diastolic compliance by early:late peak filling velocity ratio was analysed. The fundus oculi was also observed. Three subsets of hypertensives were obtained by dividing the 383 essential hypertensives on the basis of their AER:<11 (group A), 11<20 (group B) and >20 µg/min (group C) Main outcome measures Microalbuminuria, creatinine clearance, PRA, ABPM, LVMI, LVMH, early Mate peak filling velocity ratio, hypertensive retinopathy Results Among the 383 essential hypertensives, AER was < 11 µg/min in 55% of the patients (group A), 18% had AER in the range 11-20µg/min (group B) and 27% had AER >20 µg/min (group C). In the entire essential hypertensive population the prevalence of left ventricular hypertrophy was 44.39% and hypertensive retinopathy was observed in 54.83%. Moreover, AER significantly correlated with clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP), with 24 SBP and DBP and with 24 h daytime and night-time mean blood pressure (MBP). AER was correlated also with LVMH and creatinine clearance. The analysis of the three subsets revealed no differences in age, body mass index, serum creatinine level and PRA. Group C in comparison with group A showed higher values of clinic SBP, 24 h SBP, DBP and MBP, and of daytime and nighttime MBP. Furthermore, in group C, LVMI and LVMH were significantly greater than in group A, with a prevalence of left ventricular hypertrophy of 55% in the former group. Group C showed a prevalence of hypertensive retinopathy of 69% whereas in group A the prevalence was 48%. In group C, AER was significantly correlated with serum creatinine level Conclusion The transversal phase of our research, performed in a homogeneous population of Caucasian essential hypertensives with no metabolic disturbances, confirms the relationship between blood pressure pattern and early glomerular changes in essential hypertensives without overt proteinuria. Furthermore, these results emphasize the role of microalbuminuria as a marker of early cardiac, renal and retinal structural and functional changes in essential hypertension. The longitudinal study, which is in progress, will confirm the prognostic value of microalbuminuria in essential hypertension

Value of Home Blood Pressures as Predictor of Target Organ Damage in Mild Arterial Hypertension

Background Home blood pressure measurement has gained increasing importance for the management of hypertensive patients. The aim of our study was to compare levels of clinic (CBP), ambulatory (ABP), and home blood pressure (HBP) measurements, and their relationships with various indexes of target organ damage in I–II grade essential hypertension. Design and methods Thirty-eight essential hypertensives underwent evaluation of clinic, ambulatory and home blood pressures. Each patient recorded HBP for 2 days with a digital BP monitor three times daily, the first time on the same day during which ABP monitoring was simultaneously performed. Moreover, in all subjects electrocardiogram recording, echocardiographic study, microalbuminuria assay and fundus oculi examination were obtained. Results The average HBPs obtained on the first day, in particular systolic values, were quite similar to mean daytime ambulatory BP recorded on the same day. Clinic BP, both systolic and diastolic, showed no significant correlation with left ventricular mass index (LVMI) and with albumin excretion rate (AER), whereas a correlation barely significant was observed with an index of global target organ damage (GTODi), including cardiac, renal and retinal parameters. On the contrary, home blood pressures, especially those recorded on the second day, correlated significantly, and more tightly than clinic BP, with LVMI, AER and GTODi. Conclusions Our study seems to justify the adoption of home BP monitoring in the management of hypertensive patients, as a useful complement to clinical readings, and may provide additional prognostic information.

Left ventricular hypertrophy and geometry in hypertensive patients with chronic kidney disease.

Objective To evaluate the prevalence of left ventricular hypertrophy (LVH) and left ventricular geometry in a group of 293 hypertensive patients with stage 2–5 chronic kidney disease (CKD), compared with 289 essential hypertensive patients with normal renal function. Methods All patients underwent echocardiographic examination. Patients on stage 1 CKD, dialysis treatment, or with cardiovascular diseases were excluded. Results LVH was observed in 47.1% of patients with CKD and in 31.14% of essential hypertensive patients (P < 0.0001). We found increasingly higher left ventricular diameters, thicknesses, and mass from stage 2 to 5 CKD. Distribution of concentric and eccentric LVH was not different between the two groups. However, after introducing mixed hypertrophy, the difference between the two groups group was disclosed (P = 0.027). The prevalence of inappropriate left ventricular mass was 52.6% in patients with CKD vs. 30.5% in essential hypertensive patients (P < 0.0001). Multiple regression analysis confirmed that the association between renal function and left ventricular mass (β −0.287; P < 0.0001) was independent by potential confounders. From stage 4 to 5, the significant increase of left ventricular mass was due to growth in posterior wall thickness rather than end-diastolic diameter. Diastolic function was significantly worse in patients with CKD, especially in more advanced stages. Conclusion Our study confirms that LVH is highly prevalent in patients with CKD; in this population, LVH is often inappropriate and characterized by the simultaneous increase of wall thicknesses and diameters.

The progressive pathway of microalbuminuria: from early marker of renal damage to strong cardiovascular risk predictor.

There is clear evidence that urinary albumin excretion levels, even below the cut-off values currently used to diagnose microalbuminuria, are associated with an increased risk of cardiovascular events. The relationships of microalbuminuria with a variety of risk factors, such as hypertension, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced cardiovascular risk conferred by microalbuminuria. Nonetheless, several studies showed that the association between microalbuminuria and cardiovascular disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between microalbuminuria and cardiovascular risk remain incompletely understood. The simple search for microalbuminuria in hypertensive patients may enable the clinician to better assess absolute cardiovascular risk, and its identification may induce physicians to encourage patients to make healthy lifestyle changes and perhaps would prompt to more aggressive modification of standard cardiovascular risk factors.

Epidemiology and pathophysiology of left ventricular abnormalities in chronic kidney disease: a review

INTRODUCTION Cardiovascular diseases are highly prevalent in patients with chronic kidney disease (CKD), and represent the major hazard for mortality in this population. Anomalies of left ventricular (LV) structure and function are very frequent too among CKD patients, and show a negative impact on cardiovascular prognosis. METHODS We searched PubMed for manuscripts regarding left ventricular hypertrophy (LVH) in CKD. Definition of LVH was different according to different studies. RESULTS In patients with end-stage renal disease, the prevalence of LVH is higher than 70%. Studies in patients with less advanced CKD have reported increasing prevalence of LVH along with declining renal function. However, there is relatively wide heterogeneity in the prevalence of LVH in different studies, according to the characteristics of the population studied, the method chosen to estimate glomerular filtration rate and the definition of LVH. CONCLUSIONS Hypertension, alterations of fluid and electrolyte balance and anemia are identified as the major determinants of LVH in CKD. However, beyond hemodynamic factors, other factors, such as an inappropriate activation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation and collagen and muscle cell growth factors may have a relevant role. LV diastolic dysfunction is also very frequent among CKD patients and is associated with risk of heart failure and with mortality; impairment of diastolic function in patients with CKD may occur very early, even in the absence of LVH. Early detection of LVH and LV dysfunction in CKD could yield an improvement in the adverse cardiovascular outcomes of CKD patients.

Acute effects of coffee on endothelial function in healthy subjects

Background/Objectives:Coffee is the most widely consumed beverage in the world, but its effect on the cardiovascular system has not been fully understood. Coffee contains caffeine and antioxidants, which may influence endothelial function, both of which have not yet been investigated. The objective of this study was to investigate the acute effects of coffee on endothelial function measured by brachial artery flow-mediated dilation (FMD).Subjects/Methods:A total of 20 (10 males and 10 females) healthy non-obese subjects underwent a double-blind, crossover study. Subjects ingested one cup of caffeinated (CC) and one cup of decaffeinated (DC) Italian espresso coffee in random order at 5- to 7-day intervals.Results:Following CC ingestion, FMD decreased progressively and significantly (mean±s.e.m.: 0 min, 7.7±0.6; 30 min, 6.3±0.7; 60 min, 6.0±0.8%; ANOVA (analysis of variance), P<0.05), but it did not significantly increase after DC ingestion (0 min, 6.9±0.6; 30 min, 8.1±0.9; 60 min, 8.5±0.9%; P=0.115). Similarly, CC significantly increased both systolic and diastolic blood pressure; this effect was not observed after DC ingestion. Blood glucose concentrations remained unchanged after ingestion of both CC and DC, but insulin (0 min, 15.8±0.9; 60 min, 15.0±0.8 μU/ml; P<0.05) and C-peptide (0 min, 1.25±0.09; 60 min, 1.18±0.09 ng/ml; P<0.01) blood concentrations decreased significantly only after CC ingestion.Conclusions:CC acutely induced unfavorable cardiovascular effects, especially on endothelial function. In the fasting state, insulin secretion is also likely reduced after CC ingestion. Future studies will determine whether CC has detrimental clinically relevant effects, especially in unhealthy subjects.

Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients.

Objectives.  To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid‐femoral pulse wave velocity (PWV), as an index of aortic stiffness.

Glycaemic variability using continuous glucose monitoring and endothelial function in the metabolic syndrome and in Type 2 diabetes.

Diabet. Med. 27, 872–878 (2010)

Endothelin-1 and F2-isoprostane relate to and predict renal dysfunction in hypertensive patients

BACKGROUND Hypertension and additional non-traditional risk factors can damage the kidney directly and by promoting atherogenesis. Evidence indicates that increased oxidative stress and inflammation may mediate a large part of the effects of risk factors on the kidney. We hypothesized that in hypertensive patients (HT), oxidative stress, measured as 8-ISO-prostaglandin F2alpha (8-ISO-PGF2alpha), should raise paralleling decreasing renal function and should correlate with estimated glomerular filtration rate (eGFR). METHODS In 626 HT with renal function ranging from stages 1 to 5 and 100 healthy controls, plasma levels of 8-ISO-PGF2alpha, high-sensitivity C-reactive protein (CRP), transforming growth factor-beta (TGF-beta) and endothelin-1 (ET-1) were measured. GFR was estimated by the Modification of Diet in Renal Disease study equation. RESULTS When HT were stratified according to renal function stages, 8-ISO-PGF2alpha, CRP, TGF-beta and ET-1 increased progressively and significantly with decreasing eGFR. The multiple regression analysis, considering eGFR as a dependent variable, showed that 8-ISO-PGF2alpha (beta = -0.361, P < 0.000001), ET-1 (beta = -0.197, P < 0.0001) and TGF-beta (beta = -0.170, P < 0.0004) correlated independently with eGFR. All biomarkers were good predictors of eGFR <60 ml/min/1.73 m(2) [receiver-operator-curve (ROC) areas]. ET-1 was shown to be the best predictor with a ROC area = 0.938; with a threshold of 4 pg/ml, 91% sensitivity and 85% specificity were observed, whereas 8-ISO had a ROC area = 0.931, and for a threshold of 329 pg/ml, sensitivity and specificity were 89%, respectively. In contrast, CRP showed the lower predictive value with a ROC area = 0.917; with a threshold of 2.52 mg/l, an 87% sensitivity and an 83% specificity were obtained. CONCLUSIONS Our findings are a clear-cut demonstration of a strong and negative correlation of both oxidative stress and ET-1 with renal function stages in HT. ET-1 and 8-isoprostane are predictive of eGFR.