Genetic Polymorphisms of the Natriuretic Peptide System in the Pathogenesis of Cardiovascular Disease: What Lies on the Horizon?

BACKGROUND: The natriuretic peptide hormone family includes various proteins characterized by similar chemical structure and shared biological functions, with important effects on the cardiovascular system. Accordingly, these molecules are widely recognized as key clinical biomarkers in the diagnosis and monitoring of heart failure, hypertension, and coronary heart disease. CONTENT: Several single-nucleotide polymorphisms have been recently identified in genes associated with the natriuretic system. This review provides an overview of new insights into the functional role of these genetic variants, as well as their impact on cardiovascular physiopathology and drug response. CONCLUSIONS: Noteworthy relationships between some specific polymorphisms and clinical correlates of cardiovascular disease have emerged. Nevertheless, future confirming studies are needed to substantiate the clinical relevance of such variants

Oxidative Stress as a predictor of cardiovascular events in coronari artery disease patients

Abstract Background: Enhanced oxidative stress has been associated with atherosclerosis and coronary artery disease (CAD). However, the predictive value of circulating oxidative stress biomarkers for cardiovascular events (CE) in patients with CAD has remained poorly understood. Aim: To assess the prognostic significance of reactive oxygen metabolites, estimated as index of oxidative stress in serum samples by means of a commercial kit (ROMs, Diacron, Italy) on the rate of mortality and major adverse CE (MACE) in CAD. Methods: A study of 93 consecutive patients with angiographically documented CAD (75 males, age: 68?10 years, mean?SD) was made during a mean follow-up of 66 months until the occurrence of one of the following CE: cardiac and all cause death, non-fatal myocardial infarction and coronary revascularization [percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG)]. Patient data were retrospectively collected from the Institute\u27s electronic databank that saves demographic, clinical, instrumental and follow-up data of all patients admitted to our department. Results: The Kaplan-Meier survival estimates showed a significantly worst outcome in patients presenting elevated ROM level (>75th percentile, corresponding to 481 AU) (log rank=11, 7.5, 5.1; p<0.001, p<0.01, p<0.05 for cardiac and all cause death and MACEs, respectively). In a multivariate Cox regression model, elevated oxidative stress remained a significant predictor of cardiac and all cause death [hazard ratio (HR) 3.9, 95% confidence interval, 95% (CI) 1.4-11.1, p=0.01; HR=2.6, 95% CI 1.1-6.2, p=0.02) and MACE (HR=1.8, 95% CI 1.1-3.1, p=0.03)]. Conclusions: The estimation of ROMs may represent an additional prognostic tool in the assessment of CE in CAD patients

Hormone replacement therapy and cardioprotection. A new dawn? A statement of the \u27Gruppo di studio sulle malattie cardiovascolari nella donna\u27 of the societ? italiana di cardiologia on hormone replacement therapy in postmenopausal women

Cardiovascular disease is the leading cause of death in women in western countries. Despite preventive strategies, in the past decades, the incidence of cardiovascular events has shown a decline in men but a rise in women, matching the growth of the population of postmenopausal women. Several epidemiological findings suggest the causative pathophysiological role of ovarian hormone deficiency in the development of cardiovascular disease in women. Observational and randomized studies have suggested that hormone replacement therapy in early postmenopause could be beneficial from a cardiovascular point of view. Conversely, aging, time since menopause and presence of cardiovascular risk factors or cardiovascular disease may decrease its efficacy and increase the risk of cardiovascular events. It is plausible that the unfavorable effects of the estrogen/progestin combination used in the randomized studies are not related to the hormone preparation per se but rather to the use of hormones in the less receptive group of women, older and with cardiovascular risk factors. Clinical judgment, choice of the right dose and estrogen/ progestin combination are of pivotal importance to maximize the beneficial effect of estrogen replacement therapy/hormone replacement therapy, especially if given within a reasonable time after the menopause to the women who need the therapy for the relief of menopausal symptoms

Cyclooxygenase-2 Induction after Oral Surgery Does Not Entirely Account for Analgesia after Selective Blockade of Cyclooxygenase 2 in the Preoperative Period

Background The administration of selective cyclooxygenase-2 inhibitors before surgery is regarded as an innovative option to manage postoperative pain. This study was designed to (1) examine the efficacy of preoperative cyclooxygenase-2 blockade on postoperative oral pain and (2) compare pain intensity with prostaglandin E2 (PGE2) production and cyclooxygenase isoform (cyclooxygenase-1, cyclooxygenase-2) messenger RNA (mRNA) expression at the surgical site during the postoperative period. Methods Sixty patients with impacted lower third molars were randomly allocated to three single-dose treatment groups--placebo, 50 mg rofecoxib, or 550 mg naproxen--1 h before extraction. Pain intensity was evaluated with categorical and visual analog scales every 30 min from 90 to 240 min after surgery. At these times, PGE2 production in the alveolar socket was also evaluated. Cyclooxygenase-1 and cyclooxygenase-2 mRNA expression was examined by reverse-transcription polymerase chain reaction in gingival specimens collected during tooth removal and 240 min after surgery. Results Pain intensity and PGE2 production in the placebo group increased throughout the observation period. Naproxen prevented pain and decreased PGE2 release at all time points. Rofecoxib reduced PGE2 production versus placebo from 150 min onward, while inducing analgesia through the whole observation period. mRNA assay in gingival specimens collected at tooth extraction revealed cyclooxygenase-1 expression, whereas cyclooxygenase 2 was undetectable. At the end of observation, cyclooxygenase-1 mRNA expression was unchanged, whereas cyclooxygenase-2 mRNA was significantly induced. Conclusions This study indicates that preoperative administration of a selective cyclooxygenase-2 inhibitor ensures effective control of postoperative pain. It is suggested that the selective blockade of inducible cyclooxygenase 2 at the surgical site does not entirely account for the analgesic action occurring in the postoperative period

Gender differences and cardiometabolic risk. the importance of the risk factors

Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes: proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they become synergistic, doubling the risk of developing cardiovascular diseases and causing a 1.5-fold increase in all-cause mortality. We will highlight gender differences in the epidemiology, etiology, pathophysiology, and clinical expression of the aforementioned Mets components. Moreover, we will discuss gender differences in new biochemical markers of metabolic syndrome and cardiovascular risk

Breakfast habits and differences regarding abdominal obesity in a cross-sectional study in Spanish adults: The ANIBES study

Background: Previous studies have indicated that breakfast has a protective effect against obesity. The aim of this study was to describe the breakfast habits of the Spanish adult population and to assess the possible association between breakfast frequency and the presence of abdominal obesity, in a cross-sectional analysis of the ANIBES Study. Methods: A representative sample of 1655 Spanish adults (aged 39±12 y; (mean±sd)) from the ANIBES Study was investigated. The final field work was carried out from mid-September to November (three months) 2013. Collected data included a dietary data collected by a 3-days food record, and health, socioeconomic, physical activity and anthropometric (weight, height and waist circumference) data. Abdominal obesity was defined as having a waist-to-height ratio ≥0.5. The adults were also classified into three groups based on the number of days they ate breakfast (never (0/3 days), sometimes (1-2/3 days) and always (3/3 days)). Logistic regression analyses were used to evaluate the association between breakfast and abdominal obesity. Results: In total, 3.6% of adults skipped breakfast and 14.1% ate breakfast sometimes. Having always breakfast was negatively associated with abdominal obesity [OR = 0.738 (0.558–0.975) p = 0.033]. The odds of abdominal obesity after full adjustment (age, gender, and educational and activity level) were 1.5 times higher for those who skipped breakfast when compared to those who always have breakfast. By correcting the model considered for other variables, the odds among smokers decreased when they have breakfast sometimes [OR = 0.032 (0.003–0.387) p = 0.007] and always [OR = 0.023 (0.002–0.270) p = 0.003] comparing with smokers who skip breakfast. Conclusion: Breakfast frequency could be negatively associated with abdominal obesity, especially among smokers.ANIBES Study was financially supported by Coca Cola Iberia through an agreement with the Spanish Nutrition Foundation (FEN)

Uric Acid for Cardiovascular Risk: Dr. Jekyll or Mr. Hide?

Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that this biomarker behaves like other antioxidants, which can shift from the physiological antioxidant action to a pro-oxidizing effect according to their level and to microenvironment conditions. However, data on patients (general population or CAD cohorts) are controversial, so the debate on the role of hyperuricemia as a causative factor for CVD is still ongoing. Increasing evidence indicates UA as more meaningful to assess CVD in women, even though this aspect needs deeper investigation. It will be important to identify thresholds responsible for UA “biological shift” from protective to harmful effects in different pathological conditions, and according to possible gender-related differences. In any case, UA is a low-tech and inexpensive biomarker, generally performed at patient’s hospitalization and, therefore, easily accessible information for clinicians. For these reasons, UA might represent a useful additive tool as much as a CV risk marker. Thus, in view of available evidence, progressive UA elevation with levels higher than 6 mg/dL could be considered an “alarm” for increased CV risk

New biomarkers and traditional cardiovascular risk scores: any crystal ball for current effective advice and future exact prediction?

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