Urotensin II and the Circulatory System

Urotensin II (UII), first isolated from the spinal cord of teleost fish, is the most potent vasoconstrictor known. It is more potent than endothelin-1 and acts through UT-II, a seven-transmembrane-domain, G-protein-coupled receptor. Human UII is an 11-amino-acid cyclic peptide that is expressed in various tissues, including the central nervous system, heart, kidney, and blood vessels. It circulates in human plasma, and its plasma level is elevated in renal failure, congestive heart failure, diabetes, and portal hypertension. In the kidney, UII has vasodilatory and natriuretic effects, mediated through nitric oxide. The development of UII-receptor antagonists may provide a useful research tool, and a novel treatment for cardiorenal diseases

The relationship of circulating fibroblast growth factor 21 levels with pericardial fat: The Multi-Ethnic Study of Atherosclerosis.

Previous small studies have reported an association between circulating fibroblast growth factor 21 (FGF21) levels and pericardial fat volume in post-menopausal women and high cardiovascular disease (CVD) risk patients. In this study, we investigated the relationship of FGF21 levels with pericardial fat volume in participants free of clinical CVD at baseline. We analysed data from 5765 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) with both pericardial fat volume and plasma FGF21 levels measured at baseline. 4746 participants had pericardial fat volume measured in at least one follow-up exam. After adjusting for confounding factors, ln-transformed FGF21 levels were positively associated with pericardial fat volume at baseline (β = 0.055, p < 0.001). When assessing change in pericardial fat volume over a mean duration of 3.0 years using a linear mixed-effects model, higher baseline FGF21 levels were associated with higher pericardial fat volume at baseline (2.381 cm3 larger in pericardial fat volume per one SD increase in ln-transformed FGF21 levels), but less pericardial fat accumulation over time (0.191 cm3/year lower per one SD increase in ln-transformed FGF21 levels). Cross-sectionally, higher plasma FGF21 levels were significantly associated with higher pericardial fat volume, independent of traditional CVD risk factors and inflammatory markers. However, higher FGF21 levels tended to be associated with less pericardial fat accumulation over time. Nevertheless, such change in pericardial fat volume is very modest and could be due to measurement error. Further studies are needed to elucidate the longitudinal relationship of baseline FGF21 levels with pericardial fat accumulation

The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the Fenofibrate Intervention and Event Lowering in Diabetes study

Aims/hypothesis Circulating fibroblast growth factor 21 (FGF21) levels are often elevated in obesity, dyslipidaemia, insulin resistance and type 2 diabetes. This study investigated the relationship of plasma FGF21 levels with cardiovascular events in patients with type 2 diabetes. Methods Plasma FGF21 levels were measured at baseline in 9,697 study participants with type 2 diabetes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study by enzyme-linked immunosorbent assay. We assessed the association of FGF21 levels with incidence of different cardiovascular outcomes over 5-years. The primary outcome was total cardiovascular disease (CVD) events, and the secondary outcomes were the four individual components: coronary heart disease (CHD) events, total stroke, CVD mortality, coronary and carotid revascularization. Tertiary outcome was hospitalisation for angina pectoris. Results Higher baseline FGF21 levels were associated with higher risks of all cardiovascular outcome events after adjusting for the study treatment allocation (all p<0.01). The associations remained significant for total CVD events, and coronary and carotid revascularisation after further adjusting for confounding factors with HR (95% CI) being 1.28 (1.10, 1.50) and 1.26 (1.01, 1.56) respectively, for the highest tertile compared to the lowest tertile (overall effect p=0.002 and 0.007 respectively). The addition of FGF21 levels to a model including established CVD risk factors predicting total CVD led to a non-significant increase in the C-statistic, but resulted in significant integrated discrimination improvement and net reclassification improvement. Conclusions/interpretation Higher baseline plasma FGF21 levels were associated with higher risk of cardiovascular events in patients with type 2 diabetes

Is Human Cytomegalovirus Infection Associated with Hypertension? The United States National Health and Nutrition Examination Survey 1999–2002

PURPOSE: Recent studies have implicated the human cytomegalovirus (HCMV) as a possible pathogen for causing hypertension. We aimed to study the association between HCMV infection and hypertension in the United States National Health and Nutrition Examination Survey (NHANES). METHODS: We analyzed data on 2979 men and 3324 women in the NHANES 1999-2002. We included participants aged 16-49 years who had valid data on HCMV infection and hypertension. RESULTS: Of the participants, 54.7% had serologic evidence of HCMV infection and 17.5% had hypertension. There were ethnic differences in the prevalence of HCMV infection (P<0.001) and hypertension (P<0.001). The prevalence of both increased with age (P<0.001). Before adjustment, HCMV seropositivity was significantly associated with hypertension in women (OR = 1.63, 95% CI = 1.25-2.13, P = 0.001) but not in men. After adjustment for race/ethnicity, the association between HCMV seropositivity and hypertension in women remained significant (OR = 1.55, 95% CI = 1.20-2.02, P = 0.002). Further adjustment for body mass index, diabetes status and hypercholesterolemia attenuated the association (OR = 1.44, 95% CI = 1.10-1.90, P = 0.010). However, after adjusting for age, the association was no longer significant (OR = 1.24, 95% CI = 0.91-1.67, P = 0.162). CONCLUSIONS: In this nationally representative population-based survey, HCMV seropositivity is associated with hypertension in women in the NHANES population. This association is largely explained by the association of hypertension with age and the increase in past exposure to HCMV with age.published_or_final_versio

Cardiovascular drugs that increase the risk of new-onset diabetes

The prevalence of type 2 diabetes is increasing worldwide, and diabetes is a strong adverse prognostic factor among patients with cardiovascular (CV) disease. Four classes of drugs that are commonly used for CV risk reduction, statins, niacin, thiazide diuretics, and ß-blockers, have been shown to increase the risk of new-onset diabetes (NOD) by 9% to 43% in meta-analyses or large-scale clinical trials. Clinical predictors for drug-related NOD appear to be similar to the predictors that have been described for NOD unrelated to drugs: fasting blood glucose &gt;100 mg/dL and features of the metabolic syndrome such as body mass index &gt;30 kg/m(2), serum triglycerides &gt;150 mg/dL, and elevated blood pressure, among others. The mechanisms whereby these drugs increase the risk of NOD are incompletely understood, although different hypotheses have been suggested. Lifestyle intervention consisting of diet and exercise has been shown in multiple studies to reduce the risk of NOD by approximately 50%, with persistent benefit during long-term follow-up. In patients at high risk for NOD, niacin should be avoided, and for hypertension, an angiotensin-converting enzyme inhibitor or even a ß1-selective blocker might be a better choice than a standard ß-blocker. For thiazide diuretics and particularly statins, benefit in terms of CV event reduction outweighs the risk of NOD

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely