Is increased uric acid a risk factor or a defensive response? The Campania Salute Network.

BACKGROUND AND AIMS: Circulating uric acid (UA) is positively associated with body mass index (BMI), blood glucose, blood pressure (BP), markers of inflammation, and altered lipid profile. UA has also anti-oxidative properties which might be beneficial for cardiovascular (CV) system. It is still debated whether or not UA is independently associated with increased CV morbidity and/or mortality. METHODS AND RESULTS: We studied prognostic impact of UA in 8833 hypertensive adults (mean age 53 ± 12 yrs, 3857 women) from the Campania Salute Network, without prevalent CV disease and more than stage 3 CKD. We calculated standardized UA Z-score, adjusted for age, sex, glomerular filtration rate, and BMI. Low and high UA and UA Z-score quartiles were compared to the 2 middle quartiles assumed to be "normal". Prevalence of obesity and diabetes was higher in low and high than in normal UA Z-score group (all p < 0.001). Systolic BP, left ventricular mass, carotid intima thickness were significantly higher and ejection fraction was reduced in the presence of high UA Z-score (all p < 0.001). Over 33-months average follow-up, incident major CV end-points (MACE) were not significantly different among low, normal and high UA or UA Z-score. In the latter analysis, however, incident MACE tended to be more frequent in the low than the high UA Z-score. Despite the results of multivariable analyses, the effect of less aggressive therapy in low UA Z-score cannot be excluded with certainty. CONCLUSION: In treated hypertensive patients, high levels of UA normalized for major biological determinants do not independently predict CV outcome. CLINICALTRIALS. GOV IDENTIFIER: NCT02211365.

The possible role of chromosome X variability in hypertensive familiarity.

Familiarity participates in the pathogenesis of hypertension, although only recently, whole genome studies have proposed regions of the human genome possibly involved in the transmission of the hypertensive phenotype. Although studies have mainly focused on autosome, hitherto the influence of sex on familial transmission of hypertension has not been considered. We analysed the database of the Campania Salute Network of Hypertension center of the Federico II University Hospital of Naples (Italy), using dichotomous variables for paternal and maternal familiarity and gender (male and female) of 12 504 hypertensive patients (6868 males and 5636 females) and 6352 controls (3484 males and 2868 females), totaling 18 856 subjects. In the hypertensive group, familiarity was present in 75% of cases with odds of 3.77 and in only 26% of the normotensives with odds of 0.94. The odds ratio (OR) indicated that familiarity increases the risk of developing hypertension by 2.91 (95% confidence interval (CI)=2.67-3.17, P<0.001) times. Additionally, maternal familiarity was 37% (OR=3.01, 95% CI=2.66-3.41, P<0.001), paternal familiarity was 21% (OR=2.31, 95% CI=2.01-2.68, P<0.001) and the double familiarity was 17% (OR=3.45, 95% CI=2.87-4.01, P<0.001), thus suggesting a plausible association between maternal familiarity and development of hypertension; this finding was observed both in male and in female patients, although the phenomenon was larger in males. Given the dominance of maternal transmission in males, by genome-wide analysis of the X chromosome, we found two regions that were differently distributed in male hypertensives with maternal hypertension. Our data highlight the importance of genetic variants in the X chromosome to the maternal transmission of the hypertensive phenotype.

Identification of phenotypes at risk of transition from diastolic hypertension to isolated systolic hypertension.

Little is known about the potential progression of hypertensive patients towards isolated systolic hypertension (ISH) and about the phenotypes associated with the development of this condition. Aim of this study was to detect predictors of evolution towards ISH in patients with initial systolic-diastolic hypertension. We selected 7801 hypertensive patients free of prevalent cardiovascular (CV) diseases or severe chronic kidney disease and with at least 6-month follow-up from the Campania Salute Network. During 55±44 months of follow-up, incidence of ISH was 21%. Patients with ISH at the follow-up were significantly older (P<0.0001), had longer duration of hypertension, higher prevalence of diabetes and were more likely to be women (all P<0.0001). They exhibited higher baseline left ventricular mass index (LVMi), arterial stiffness (pulse pressure/stroke index), relative wall thickness (RWT) and carotid intima-media thickness (IMT; all P<0.001). Independent predictors of incident ISH were older age (odds ratio (OR)=1.14/5 years), female gender (OR=1.30), higher baseline systolic blood pressure (OR=1.03/5 mm Hg), lower diastolic blood pressure (OR=0.89/5 mm Hg), longer duration of hypertension (OR=1.08/5 months), higher LVMi (OR=1.02/5 g m(-2.7)), arterial stiffness (OR=2.01), RWT (OR=1.02), IMT (OR=1.19 mm(-1); all P<0.0001), independently of antihypertensive treatment, obesity, diabetes and fasting glucose (P>0.05). Our findings suggest that ISH is a sign of aggravation of the atherosclerotic disease already evident by the target organ damage. Great efforts should be paid to prevent this evolution and prompt aggressive therapy for arterial hypertension should be issued before the onset of target organ damage, to reduce global CV risk.

Functional foods and cardiometabolic diseases* International Task Force for Prevention of Cardiometabolic Diseases.

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional dietadopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health.

Benefits of combination therapy in hypertensive patients with associated coronary artery disease: a subgroup with specific demands.

Although prevention of coronary artery disease (CAD) is one of the main goals of antihypertensive therapy, when first seen hypertensive patients often have associated CAD. These patients need a therapy that can exert an acute anti-ischemic action, such as ad hoc relief of angina pectoris, and can also reduce the incidence of myocardial infarction (MI) or reinfarction. Reduction in blood pressure (BP) alone does not appear to be adequate because in hypertensive patients CAD is a complex and multifactorial process involving not only hemodynamic, neurohormonal, and metabolic factors but also hypertension-induced myocardial and vascular structural changes, which appear independently to contribute to risk for CAD. In theory, antihypertensive combination therapy, by summing the different effects of various drugs, appears to have a greater capacity for comprehensive management of hypertensive patients with CAD. Simultaneous administration of angiotensin-converting enzyme (ACE) inhibitors and calcium-channel blockers appears to be particularly effective. In several clinical trials with long-term follow-up, ACE inhibitor therapy has been associated with a substantial reduction in the risk for major ischemic events. The antiproliferative action of ACE inhibitors on myocardium and the vascular wall, their hemodynamic effects, antiatherogenic actions, neurohormonal attenuation, and certain genetic issues may account for the ability of this class of drugs to reduce the risk for CAD-related events. Although ACE inhibitors can be expected to increase coronary blood flow when the renin-angiotensin system is activated and to reduce BP, ventricular filling pressure, and sympathetic drive, thus far an acute anti-ischemic action of these drugs has not been demonstrated. Unlike ACE inhibitors, which usually have class-specific effects, there are important differences in the clinical effects of various calcium antagonists. The first generation of dihydropyridine calcium-entry blockers has failed to demonstrate efficacy in secondary prevention of coronary artery events. However, verapamil reduces mortality in patients with normal left ventricular function. The antihypertensive efficacy of verapamil, its antiatherogenic action, and its ability to reverse left ventricular hypertrophy, to improve diastolic function, and to interfere with endothelium-derived contracting factors may also account for the improved survival of patients with CAD treated with this drug. Moreover, verapamil is also effective in the treatment of all types of angina because it reduces myocardial oxygen consumption as a result of its hypotensive effect and its ability to reduce heart rate, and it may also improve oxygen delivery to the myocardium because of its action on coronary vasodilatation. It is also important to consider that ACE inhibitors and calcium antagonists often induce the same beneficial effects through different mechanisms, thus allowing a synergistic action when the two classes of drugs are administered together.

[Submucosal lipomas of the colon (considerations apropos of 3 clinical cases)]. / I lipomi sottomucosi del colon (considerazioni a proposito di tre casi clinici).

Submucous colonic lipoma is relatively rare and can be the cause of important diagnostic and consequently therapeutic problems. The AA. reexamine the anatomo pathological and clinical features and the diagnostic and therapeutic problems, and refer 3 cases observed one of which was localized in the ileo-cecal valve. The AA. remark that radiological and endoscopic investigations and laparotomy features also can simulate a malignant tumor and address to the surgical technics of the oncologic surgery.