14 research outputs found
Site-dependency of the E/e' ratio in predicting invasive left ventricular filling pressure in patients with suspected or ascertained coronary artery disease.
No full textPURPOSE:
To test the accuracy of different mitral annular sites of the E/e' ratio in predicting invasive left ventricular filling pressure (LVFP) in patients hospitalized for coronary artery disease (CAD).
METHODS:
Forty-one patients with suspected or ascertained chronic CAD underwent non-invasive estimation of LVFP the same day as coronary angiography combined with right catheterization for pulmonary capillary wedge pressure (PCWP) assessment. The ratio between E velocity and early diastolic velocity of the mitral annulus (e') was calculated as a surrogate of PWCP by (i) averaging septal and lateral e' (E/e'A2); (ii) averaging septal, lateral, inferior, anterior (E/e'A4); (iii) using the sole septal (E/e'S); or (iv) lateral annulus (E/e'L). Patients were divided in two groups according to the PCWP: 25 with the PCWP <18 mmHg and 16 with the PCWP ≥ 18 mmHg.
RESULTS:
The two groups were comparable for gender, body mass index, blood pressure, heart rate (HR), E/A ratio, and deceleration time. The ejection fraction (EF) was lower and left atrial volume index (LAVi) greater (both P < 0.02) in patients with the PCWP ≥ 18 mmHg. They also exhibited higher E/e'S (P < 0.05), E/e'L (P < 0.0001), E/e'A2, and E/e'A4 (both P < 0.005) than patients with the PCWP <18 mmHg. In pooled groups, after adjusting for HR EF and LAVi, E/e'L (β = 0.42, P < 0.01), E/e'A2 (β = 0.32, P < 0.05), and E/e'A4 (β = 0.31, P < 0.05) were all independently associated with PWCP. E/e'L ≥ 16.2 predicted PCWP ≥18 mmHg with the highest diagnostic accuracy (AUC = 0.826), sensitivity (81.3%), and specificity (80%).
CONCLUSIONS:
In patients with CAD, E/e'L is the most accurate parameter in predicting abnormally increased LVFP
La hs-PCR non predice lo sviluppo di ipertensione arteriosa in un campione di popolazione adulta maschile: Olivetti Heart Study, follow-up 8 anni
No full textGenetic variations at the endocannabinoid type 1 receptor gene (CNR1) are associated with obesity phenotypes in men.
No full textThe endocannabinoid system modulates food intake and body weight in animal models. Treatment with the cannabinoid type 1 receptor blocker, rimonabant, reduces body weight in obese individuals. OBJECTIVE: The aim of this study was to determine whether single nucleotide polymorphisms of the gene encoding cannabinoid type 1 receptor, CNR1, are associated with body fat mass and distribution in two independent samples of white European adult men. DESIGN, SETTING, AND PARTICIPANTS: The 3813A/G and 4895A/G single nucleotide polymorphisms at the exon 4 of CNR1 were genotyped in 930 participants to the Olivetti Prospective Heart Study (OPHS) in Southern Italy and in 216 participants to the Wandsworth Heart and Stroke Study in the United Kingdom. Retrospective analysis was also performed on an OPHS subsample (n = 360) for which anthropometric data from 1987 and 1994-1995 examinations were available. MAIN OUTCOME MEASURES: CNR1 genotypes and anthropometric measures of body fat distribution were determined. RESULTS: In the OPHS study, the 3813G allele was associated with increased subscapular skinfold thickness (24.2 +/- 9.1 vs. 22.8 +/- 7.7 mm; P = 0.031) and waist circumference (WC) (99.1 +/- 8.8 vs. 97.7 +/- 8.8 cm; P = 0.050). No association was observed with 4895A/G variant. Haplotype analysis confirmed that the unique haplotype carrying the 3813G was associated with increased WC and subscapular skinfold thickness. Similar results were observed in the OPHS retrospective subsample and the Wandsworth Heart and Stroke Study sample. In the latter, the 3813G was associated with increased WC (96.8 +/- 11.3 vs. 91.6 +/- 10.4 cm; P = 0.006). CONCLUSIONS: Genetic variants at CNR1 are associated with obesity-related phenotypes in men. The detection of polymorphic variants in genes involved in the process of fat accumulation may help identify specific targets for pharmacological treatment of obesity and related metabolic abnormalitie
LA STIMA NON INVASIVA DELLE PRESSIONI DI RIEMPIMENTO NEL PAZIENTE CON CARDIOPATIA ISCHEMICA: PARAMETRI DOPPLER A CONFRONTO.
No full textCirculating leptin levels predict the development of metabolic syndrome in middle-aged men: an 8-year follow-up study.
No full textDiagnostic criteria for metabolic syndrome: a comparative analysis in an unselected sample of adult male population.
No full textSLC2A9 is a high-capacity urate transporter in humans
No full textBackground
Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal
elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and
cardiovascular disease. Recent genome-wide association scans have found common genetic
variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene
encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed
in the proximal nephron, a key site for urate handling in the kidney. We investigated whether
SLC2A9 is a functional urate transporter that contributes to the longstanding association
between urate and blood pressure in man.
Methods and Findings
We expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms
mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200–500
lM). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose
or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45-
to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is
facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the
uricosuric benzbromarone in a dose-dependent manner (Ki=27μM). Furthermore, we found
urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing
SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due
to SLC2A9, and not another urate transporter, we showed that urate transport was diminished
by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that
genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with
common variation at SLC2A9 leading to increased serum urate. We found no evidence of
association with hypertension (odds ratio 0.98, 95% confidence interval [CI] 0.9 to 1.05, p > 0.33)
by meta-analysis of an SLC2A9 variant in six case–control studies including 11,897 participants. In
a separate meta-analysis of four population studies including 11,629 participants we found no
association of SLC2A9 with systolic (effect size -0.12 mm Hg, 95% CI -0.68 to 0.43, p=0.664) or
diastolic blood pressure (effect size -0.03 mm Hg, 95% CI -0.39 to 0.31, p = 0.82).
Conclusions
This study provides evidence that SLC2A9 splice variants act as high-capacity urate
transporters and is one of the first functional characterisations of findings from genome-wide
association scans. We did not find an association of the SLC2A9 gene with blood pressure in this
study. Our findings suggest potential pathogenic mechanisms that could offer a new drug
target for gout
Polymorphisms in the WNK1 gene are asociated with blood pressure variation and urinary potassium excretion
No full textWNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23–4.9), DBP 1.9 mmHg (95%CI:0.7–3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0–1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7×10−3, combined with BRIGHT data-set p = 2×10−4, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH
Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion
No full textWNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study
case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p= 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in
intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23–4.9), DBP 1.9 mmHg (95%CI:0.7–3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0–1.7]).We genotyped this variant in six independent populations (n= 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 761023, combined with BRIGHT data-set p = 261024, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p,1027). We identified several common haplotypes to be associated with increased BP and multiple low frequency haplotypes significantly associated with lower BP (.10 mmHg reduction) and risk for hypertension (OR,0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH
