No development of hypertension in the hyperuricemic liver-Glut9 knockout mouse.

Urate is the metabolic end point of purines in humans. Although supra-physiological plasma urate levels are associated with obesity, insulin resistance, dyslipidemia, and hypertension, a causative role is debated. We previously established a mouse model of hyperuricemia by liver-specific deletion of Glut9, a urate transporter that provides urate to the hepatocyte enzyme uricase. These LG9 knockout mice show mild hyperuricemia (120 μmol/l), which can be further increased by the urate precursor inosine. Here, we explored the role of progressive hyperuricemia on the cardiovascular function. Arterial blood pressure and heart rate were periodically measured by telemetry over 6 months in LG9 knockout mice supplemented with incremental amounts of inosine in a normal chow diet. This long-term inosine treatment elicited a progressive increase in uricemia up to 300 μmol/l; however, it did not modify heart rate or mean arterial blood pressure in LG9 knockout compared with control mice. Inosine treatment did not alter cardiac morphology or function measured by ultrasound echocardiography. However, it did induce mild renal dysfunction as revealed by higher plasma creatinine levels, lower glomerular filtration rate, and histological signs of chronic inflammation and fibrosis. Thus, in LG9 knockout mice, inosine-induced hyperuricemia was not associated with hypertension despite partial renal deficiency. This does not support a direct role of urate in the control of blood pressure.

Prevalence of iodine inadequacy in Switzerland assessed by the estimated average requirement cut-point method in relation to the impact of iodized salt.

OBJECTIVE: To assess the iodine status of Swiss population groups and to evaluate the influence of iodized salt as a vector for iodine fortification. DESIGN: The relationship between 24 h urinary iodine and Na excretions was assessed in the general population after correcting for confounders. Single-day intakes were estimated assuming that 92 % of dietary iodine was excreted in 24 h urine. Usual intake distributions were derived for male and female population groups after adjustment for within-subject variability. The estimated average requirement (EAR) cut-point method was applied as guidance to assess the inadequacy of the iodine supply. SETTING: Public health strategies to reduce the dietary salt intake in the general population may affect its iodine supply. SUBJECTS: The study population (1481 volunteers, aged ≥15 years) was randomly selected from three different linguistic regions of Switzerland. RESULTS: The 24 h urine samples from 1420 participants were determined to be properly collected. Mean iodine intakes obtained for men (n 705) and women (n 715) were 179 (sd 68.1) µg/d and 138 (sd 57.8) µg/d, respectively. Urinary Na and Ca, and BMI were significantly and positively associated with higher iodine intake, as were men and non-smokers. Fifty-four per cent of the total iodine intake originated from iodized salt. The prevalence of inadequate iodine intake as estimated by the EAR cut-point method was 2 % for men and 14 % for women. CONCLUSIONS: The estimated prevalence of inadequate iodine intake was within the optimal target range of 2-3 % for men, but not for women.

Exaggerated pulmonary hypertension and right ventricular dysfunction in high-altitude dwellers with patent foramen ovale.

BACKGROUND: There is considerable interindividual variability in pulmonary artery pressure among high-altitude (HA) dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia, and it is thought to aggravate these problems. METHODS: We searched for a PFO (transesophageal echocardiography) in healthy HA dwellers (n = 22) and patients with chronic mountain sickness (n = 35) at 3,600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular (RV) function, pulmonary artery pressure, and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure. RESULTS: The prevalence of PFO (32%) was similar to that reported in low-altitude populations and was not different in participants with and without chronic mountain sickness. Its presence was associated with RV enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25 ± 7 mm Hg vs 15 ± 9 mm Hg, P < .001) and a blunted increase in fractional area change of the right ventricle (3% [-1%, 5%] vs 7% [3%, 16%], P = .008) during mild exercise. CONCLUSIONS: These findings show, we believe for the first time, that although the prevalence of PFO is not increased in HA dwellers, its presence appears to facilitate pulmonary vasoconstriction and RV dysfunction during a mild physical effort frequently associated with daily activity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

Elevated hypertension risk for African-origin populations in biracial societies : Modeling the Epidemiologic Transition Study.

OBJECTIVES: Blood pressures in persons of African descent exceed those of other racial/ethnic groups in the United States. Whether this trait is attributable to the genetic factors in African-origin populations, or a result of inadequately measured environmental exposures, such as racial discrimination, is not known. To study this question, we conducted a multisite comparative study of communities in the African diaspora, drawn from metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. METHODS: At each site, 500 participants between the age of 25 and 49 years, with approximately equal sex balance, were enrolled for a longitudinal study of energy expenditure and weight gain. In this study, we describe the patterns of blood pressure and hypertension observed at baseline among the sites. RESULTS: Mean SBP and DBP were very similar in the United States and South Africa in both men and women, although among women, the prevalence of hypertension was higher in the United States (24 vs. 17%, respectively). After adjustment for multiple covariates, relative to participants in the United States, SBP was significantly higher among the South Africans by 9.7 mmHg (P < 0.05) and significantly lower for each of the other sites: for example, Jamaica: -7.9 mmHg (P = 0.06), Ghana: -12.8 mmHg (P < 0.01) and Seychelles: -11.1 mmHg (P = 0.01). CONCLUSION: These data are consistent with prior findings of a blood pressure gradient in societies of the African diaspora and confirm that African-origin populations with lower social status in multiracial societies, such as the United States and South Africa, experience more hypertension than anticipated based on anthropometric and measurable socioeconomic risk factors.

Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults between 1992 and 2007

PURPOSE: to assess the trends of prevalence of self-reported cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia, diabetes) and their management for the period of 1992 to 2007 in Switzerland. METHODS: four health interview surveys conducted between 1992 and 2007 in representative samples of the Swiss population (63,782 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed after weighting. Weights were calculated by raking ratio such that the marginal distribution of the weighted totals conforms to the marginal distribution of the target population. Multivariate analysis was conducted using logistic regression. RESULTS: prevalence of all CV RFs increased between 1992 and 2007. Also, the prevalence of self-reported treatment among subjects with CV RFs increased, as confirmed by multivariate analysis: OR for hypolipidemic treatment relative to 1992: 0.64 [0.52-0.78]; 1.39 [1.18-1.65] and 2.00 [1.69-2.36] for 1997, 2002 and 2007, respectively. Still, in 2007, circa 40% of hypertensive, 60% of hypercholesterolemic and 50% of diabetic subjects weren't treated. On the other hand, there is an increase of the prevalence of controlled RFs as reported by treated subjects. This was confirmed by multivariate analysis 12.1 [12.0 - 12.2]; 4.16 [4.1 - 4.23] and 2.85 [2.79 - 2.90] for hypertension, hypercholesterolemia and diabetes, respectively, in 2007, relative to 1992. CONCLUSION: the prevalence of self-reported hypertension, hypercholesterolemia and diabetes increased between 1992 and 2007 in the Swiss population. Despite a good control of treated subjects, still a significant percentage of subjects with CV RFs are not treated.