Organ damage (OD) is an indicator of increased cardiovascular risk. Blood pressure variability (BPV) is related to greater incidence of events, regardless of the severity of hypertension. We ...investigated the relationship between ambulatory blood pressure monitoring (ABPM)-derived indices of BPV and the presence of multiple OD in primary hypertension (PH). One hundred and sixty-nine untreated patients with PH were evaluated. Systolic (SBP) and diastolic blood pressure (DBP) variability were assessed as the crude and weighted (w.) standard deviation (s.d.), and average real variability (ARV) of the mean value of 24-h, awake and asleep ABPM recordings. Left ventricular mass index, intima-media thickness, estimated-glomerular filtration rate and urinary albumin excretion were assessed as indices of cardiac, vascular and renal damage, respectively. Risk profile progressively increased starting from patients without OD to patients with only one sign of OD, and then to those with multiple OD. In addition to greater severity of the organ involvement, the only variables that were found to significantly differ between subjects with multiple and single OD were office SBP (160 ± 14 vs 154 ± 11 mm Hg, P=0.0423) and DBP (101 ± 7 vs 97 ± 8 mm Hg, P=0.0291), ambulatory arterial stiffness index (AASI) (0.60 ± 0.10 vs 0.50 ± 0.17, P=0.0158) and indices of BPV (24-h SBP s.d., 23 ± 5 vs 20 ± 6 mm Hg, P=0.0300; awake SBP s.d., 22 ± 6 vs 19 ± 6 mm Hg, P=0.0366; 24-h SBP w.s.d., 20 ± 5 vs 17 ± 5 mm Hg, P=0.0385; and 24-h SBP ARV, 18 ± 4 vs 15 ± 5 mm Hg, P=0.0420). All the above mentioned BPV parameters turned out to be determinants of multiple OD, regardless of several confounding variables, including BP levels. Therefore, in hypertensive patients increased SBP variability is associated with multiple signs of OD, regardless of BP values.
To develop and validate a model for predicting 5-year eGFR-loss in type 2 diabetes mellitus (T2DM) patients with preserved renal function at baseline.
A cohort of 504.532 T2DM outpatients ...participating to the Medical Associations of Diabetologists (AMD) Annals Initiative was splitted into the Learning and Validation cohorts, in which the predictive model was respectively developed and validated. A multivariate Cox proportional hazard regression model including all baseline characteristics was performed to identify predictors of eGFR-loss. A weight derived from regression coefficients was assigned to each variable and the overall sum of weights determined the 0 to 8-risk score.
A set of demographic, clinical and laboratory parameters entered the final model. The eGFR-loss score showed a good performance in the Validation cohort. Increasing score values progressively identified a higher risk of GFR loss: a score ≥ 8 was associated with a HR of 13.48 (12.96–14.01) in the Learning and a HR of 13.45 (12.93–13.99) in the Validation cohort.
The 5 years-probability of developing the study outcome was 55.9% higher in subjects with a score ≥ 8.
In the large AMD Annals Initiative cohort, we developed and validated an eGFR-loss prediction model to identify T2DM patients at risk of developing clinically meaningful renal complications within a 5-years time frame.
The increased atherothrombotic risk in patients with metabolic syndrome (MetS) has been classically explained by the multiplicative effect of systemic concomitant pro-atherosclerotic factors. In ...particular, centripetal obesity, dyslipidaemia, glucose intolerance, hypertension (differently combined in the diagnosis of the disease) would be expected to act as classical cardiovascular risk conditions underlying accelerated atherogenesis. In order to better understand specific atherosclerotic pathophysiology in MetS, emerging evidence focused on the alterations in different organs that could serve as both pathophysiological targets and active players in the disease. Abnormalities in adipose tissue, heart and arteries have been widely investigated in a variety of basic research and clinical studies in MetS. In this narrative review, we focus on pathophysiological activities of the liver and kidney. Considering its key role in metabolism and production of soluble inflammatory mediators (such as C-reactive protein CRP), the liver in MetS has been shown to be altered both in its structure and function. In particular, a relevant amount of the fat accumulated within this organ has been shown to be associated with different degrees of inflammation and potential insulin resistance. In humans, non-alcoholic fatty liver disease (NAFLD) has been described as the hepatic manifestation of MetS. In an analogous manner, epidemiological evidence strongly suggested a "guilty" association between MetS and chronic kidney disease (CKD). Some biomarkers of hepatic (such as C-reactive protein, TNF-alpha or other cytokines) and renal diseases (such as uric acid) associated with MetS might be particularly useful to better manage and prevent the atherothrombotic risk.
Tacrolimus is a cornerstone in the immunosuppressive therapy of kidney transplantation. The once-daily formulation of tacrolimus has been shown to improve adherence of patients without affecting ...short-term efficacy. However, long-term proof of once-daily tacrolimus efficacy and safety is still lacking. From January 2009 to November 2013, 170 clinically stable kidney transplant patients were offered to change from the ongoing twice-daily tacrolimus (TDT) formulation to a once-daily tacrolimus (ODT) regimen. Kidney transplant recipients agreeing to the change to be treated with an ODT regimen (n = 105, estimated glomerular filtration rate eGFR 57.1 ± 1.6 mL/min/1.73 m2) and patients continuing on a TDT formulation (n = 65, eGFR 52.0 ± 2.2 mL/min/1.73 m2) were prospectively followed (median follow-up time 10.4 and 12.6 years in the ODT and TDT groups, respectively, P = not significant). At the end of the follow-up, patients in both groups experienced similar eGFR (50.4 ± 2.2 vs 48.0 ± 2.7 mL/min/1.73 m2 in the ODT and TDT groups, respectively, P = not significant). No differences were observed in biopsy-proven acute rejection, overall graft survival, doubling of serum creatinine, and new onset of proteinuria. The 2 groups also had a comparable rate of death, sepsis, and neoplasia.
In conclusion, ODT appears safe and effective in stable kidney graft recipients even 10 years after transplantation. These findings support the use of ODT as a primary tacrolimus formulation in patients with kidney transplantation.
•Once-daily tacrolimus may overcome noncompliance and rejection risks.•Over the long term, once-daily tacrolimus is as safe as the twice-daily formulation.•Tacrolimus demonstrates equivalence in the rate of acute rejections, graft survival, and renal function.•Treatment with tacrolimus results in the same rate of death, sepsis, and neoplasia even 10 years after transplantation.
Abstract Background and aims The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic ...syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes. Methods and results A total of 2429 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) <60 ml/min/1.73 m2 or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women). The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03–1.18; P = 0.0060; OR 1.28, 95% CI 1.15–1.42; P < 0.0001). These associations were stronger in patients without diabetes and with normal renal function. Conclusions Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk.
A number of epidemiological studies have reported an association between serum uric acid levels and a wide variety of high-risk conditions including hypertension, insulin resistance, and kidney and ...cerebro-cardiovascular disease. All things considered, serum uric acid may induce cardiovascular and kidney events both directly and indirectly by promoting other well-known mechanisms of damage. While asymptomatic hyperuricemia is currently not considered to be an indication for urate lowering therapy, there is growing evidence indicating a linear relationship between pharmacological reduction in serum uric acid and incidence of cardiovascular and renal events.
Metabolic syndrome (MS) has been shown to predict cardiovascular events in hypertension. Recently, a new four-group left ventricular (LV) hypertrophy classification based on both LV dilatation and ...concentricity was proposed. This classification has been shown to provide a more accurate prediction of cardiovascular events, suggesting that the presence of LV dilatation may add prognostic information. We investigated the relationship between MS and the new classification of LV geometry in patients with primary hypertension. A total of 372 untreated hypertensive patients were studied. Four different patterns of LV hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The overall prevalence of MS and LV hypertrophy (LVH) was 29% and 61%, respectively. Patients with MS showed a higher prevalence of LVH (P=0.0281) and dilated LV geometries, namely eccentric dilated and concentric dilated hypertrophy (P=0.0075). Moreover, patients with MS showed higher LV end-diastolic volume (P=0.0005) and prevalence of increased LV end-diastolic volume (P=0.0068). The prevalence of LV chamber dilatation increased progressively with the number of components of MS (P=0.0191). Logistic regression analysis showed that the presence of MS entails a three times higher risk of having LV chamber dilatation even after adjusting for several potential confounding factors. MS is associated with LV dilatation in hypertension. These findings may, in part, explain the unfavourable prognosis observed in patients with MS.
Metabolic syndrome (MS) has recently been shown to be a forerunner of chronic kidney disease (CKD). Microalbuminuria (MA) is associated with both MS and CKD. This study aimed to prospectively ...investigate the relationship among MA, MS and renal outcome in non-diabetic patients with primary hypertension. A total of 790 hypertensive patients enrolled in the MAGIC study between 1993 and 1997 (mean age 49.3±10.7 years) were included in the analysis. Renal outcome was defined as the first hospitalization with a diagnosis of CKD. At baseline, 146 (19%) and 60 (7.6%) patients met MS and MA criteria, respectively. A total of 20 patients (2.5%) concomitantly showed MS and MA. After a median follow-up of 11.6 years (interquartile range 3.2 years), renal end point was reached in 15.8% of patients with MS and in 8.9% of those without it (P=0.0087). The incidence of renal events increased progressively starting from patients with neither MS nor MA, to patients with only one of these abnormalities and then to those with both. Significant interaction was observed between MS and MA. Patients with concomitant occurrence of MS and MA at baseline showed a greater than fivefold risk of renal outcome, as compared with patients with neither of these two risk factors (hazard ratio 5.46; 95% confidence interval 2.34-12.75). This risk became even higher when data were adjusted for potential confounders. MS and MA are independent and interactive predictors of renal outcome in non-diabetic patients with primary hypertension.
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Objectives. Hypertensive patients with metabolic syndrome (MS) are at greater risk for cardiovascular disease. To get a better understanding of the pathophysiology underlying this association, we ...evaluated the relationship between MS and subclinical organ damage in essential hypertensive patients.
Design and setting. A total of 354 untreated, nondiabetic patients with primary hypertension were included in the study. A modified ATP III definition for MS was used, with body mass index replacing waist circumference. Albuminuria was measured as albumin to creatinine ratio, left ventricular mass index (LVMI) was assessed by echocardiography and carotid abnormalities by ultrasonography.
Results. The prevalence of MS was 25%. Patients with MS were more likely to be smokers (P = 0.004) and had higher serum uric acid levels (P = 0.004). Moreover, they showed higher urinary albumin excretion (P = 0.0004) and LVMI (P = 0.0006), increased intima‐media thickness (P = 0.045), as well as higher prevalence of microalbuminuria (P = 0.03) and left ventricular hypertrophy (LVH; P = 0.003). After adjusting for age, gender and duration of hypertension, we found that the presence of MS entails a twofold greater risk for microalbuminuria (P = 0.04), LVH (P = 0.003) and carotid abnormalities (P < 0.05). When patients were stratified according to the number of components of MS, albuminuria (P = 0.002) and LVMI (P = 0.005) increased progressively across categories.
Conclusions. Metabolic syndrome is associated with subclinical organ damage in nondiabetic, essential hypertensive patients. These data may, in part, explain the high cardiovascular morbidity and mortality that is observed in hypertensive patients with MS.
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