Risk factors for silent myocardial ischemia in patients with well-controlled essential hypertension.

Silent myocardial ischemia (SMI) is frequently observed in patients with essential hypertension (EH). The major risk factor for SMI is uncontrolled blood pressure (BP), but SMI is also observed in patients with well-controlled BP. To evaluate the prevalence of SMI and the factors associated with SMI in EH patients with well-controlled BP. The medical records of 859 EH patients who underwent simultaneous 24-h ambulatory blood pressure monitoring (ABPM) and 24-h ambulatory electrocardiogram recording (AECG) were retrospectively evaluated. Each SMI episode was characterized by: (a) ST segment depression ≥0.5 mm; (b) duration of ST segment depression >60 s; and (c) reversibility of the ST segment depression. Overall 126 EH patients (14.7 %) had at least one episode of SMI. The SMI events were more frequent among patients with poorly controlled compared to those with well-controlled BP [86/479 (17.95 %) vs. 40/380 (10.52 %), p < 0.01]. Among EH patients with well-controlled BP, current and past smoking as well as the presence of an additional metabolic syndrome (MetS) constitutive element (obesity, impaired fasting glucose level or dyslipidemia) were significantly associated with the occurrence of SMI. In all EH patients with well-controlled BP and AECG evidence of SMI, there were one or more coronary artery stenotic lesions greater than 50 % found at coronary angiography. In EH patients who are current smokers, or have one or more additional components of a MetS there is markedly reduced benefit associated with good BP control with regard to the occurrence of myocardial ischemia: in this patient category, an AECG may help detect this condition.

Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers.

BACKGROUND: Genetic factors play a key role in the pathogenesis of hypocitraturia, a common risk factor for nephrolithiasis. The Na+-dicarboxylate cotransporter NaDC1, encoded by the sodium-dicarboxylate cotransporter (SLC13A2) gene, is a major determinant of urinary citrate excretion and its biological functions are regulated also by the vitamin D/Vitamin D receptor (VDR) biological system. The aim of this case-control study was to evaluate the possible epistatic interaction between VDR rs731236and SLC13A2 rs11567842 allelic variants in the pathogenesis of hypocitraturia. METHODS: Recurrent calcium-oxalate stone formers (SF) with or without hypocitraturia and healthy controls (C) were genotyped. Gene-gene interactions were estimated by the 1.0 software package of multifactor dimensionality reduction (MDR). RESULTS: The prevalence of VDR TT and SLC13A2 GG genotypes was higher in hypocitraturic SF compared to C (odds ratio [OR] 3.24, 95 % confidence interval [CI] 1.38-7.60 for VDR TT vs. VDR tt and OR 4.06, 95 % CI 1.75-9.42 for SLC13A2 GG vs. SLC13A2 AA ). MDR analysis indicated a significant interaction between VDR TT and SLC13A2 GG in hypocitraturic SF compared to C [OR 3.81 (2.11-6.88)]. These data are compatible with an epistatic interaction between the VDR TT and SLC13A2 GG genotypes with a significant impact on the magnitude of the effect (suppressive effect). CONCLUSIONS: These results point to an epistatic interaction between the VDR and the SLC13A2 alleles in the pathogenesis of idiopathic hypocitraturia in calcium-oxalate SF.

Meta-Analysis of the Effect of Dietary Sodium Restriction with or without Concomitant Renin-Angiotensin-Aldosterone System-Inhibiting Treatment on Albuminuria.

BACKGROUND AND OBJECTIVES: Urinary albumin excretion and/or albumin to creatinine ratio are associated with CKD and higher risk of cardiovascular events. Several studies investigated the effect of reduced dietary sodium intake on urinary albumin excretion and/or albumin to creatinine ratio in adult patient populations, but the majority was inconclusive because of insufficient statistical power. A meta-analysis of the randomized, controlled trials available could overcome this problem and lead to more definitive conclusions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic search of the online databases available (from 1996 to October of 2014) was conducted of randomized, controlled trials that expressed urinary albumin excretion or albumin to creatinine ratio as the difference between the effects of two different sodium intake regimens. For each study, the mean difference and 95% confidence intervals were pooled using a random effect model. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS: Eleven studies met the predefined inclusion criteria and provided 23 cohorts with 516 participants and 1-6 weeks of follow-up time. In the pooled analysis, an average reduction in sodium intake of 92 mmol/d was associated with a 32.1% (95% confidence interval, -44.3 to -18.8) reduction in urinary albumin excretion. The effect of sodium restriction was higher in the cohorts including patients on concomitant renin-angiotensin-aldosterone system-blocking therapy, in the studies with intervention lasting at least 2 weeks, and among participants with evidence of kidney damage. A greater reduction of urinary albumin excretion was associated with a higher decrease in BP during the intervention. The analysis of changes in albumin to creatinine ratio provided similar results. CONCLUSIONS: This meta-analysis indicates that sodium intake reduction markedly reduces albumin excretion, more so during concomitant renin-angiotensin-aldosterone system-blocking therapy and among patients with kidney damage.

Recommending salt intake reduction to the hypertensive patient: more than just lip service.

The average individual dietary salt intake largely exceeds the physiological needs almost worldwide. A direct causal association between salt intake and blood pressure levels has been clearly established. Furthermore, there is increasing evidence for additional blood pressure-independent pathways linking excess salt intake to the process of atherosclerosis. Recent meta-analyses of randomized controlled trials showed that moderate reduction of salt intake is associated with reduction of blood pressure and, in perspective, with reduction of cardiovascular and cerebrovascular events in hypertensive individuals. According to the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines for the management of hypertension, instructions to reduce dietary salt intake to the level of 5 g/day based on the WHO recommendation should be provided to all patients, regardless of their requirement for drug treatment. Unfortunately, the patients' response to this measure is heterogeneous, mainly due to variable compliance with the doctor's prescription and to a lesser extent to different individual BP salt sensitivity. This article discusses the factors affecting the probability of a successful intervention focusing in particular on the doctor's commitment to evaluate the patient's dietary habits, to point out the main sources of salt in the patient's diet, to provide the patient with adequate motivation and with proper instructions to implement gradual reduction of his/her salt intake, not disregarding the need for regular follow-up.