Anna F. Dominiczak

2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document.

Abbreviations ACE: angiotensin-converting enzyme; BP: blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; ET: endothelin; IMT: carotid intima-media thickness; JNC: Joint National Commit

2013 ESH/ESC Practice Guidelines for the Management of Arterial Hypertension

Correspondence to: Professor Giuseppe Mancia, Centro di Fisiologia Clinica e, Ipertensione, Via F. Sforza, 35, 20122, Milano, Italy. Tel: 39 039 233 3357; Fax: 39 039 322 274; E-mail: giuseppe.mancia@unimib.it, Professor Robert Fagard, Hypertension & Cardiovascular Rehab. Unit, KU Leuven, University, Herestraat 49, 3000 Leuven, Belgium. Tel: 32 16 348 707; Fax: 32 16, 343 766; E-mail: robert.fagard@uzleuven.be

Randomised comparison of percutaneous angioplasty vs continued medical therapy for hypertensive patients with atheromatous renal artery stenosis

Background: Data from randomised studies are lacking on the value of interventional procedures in the management of atheromatous renal artery stenosis. This randomised prospective trial compared the effects on blood pressure (BP) and renal function of percutaneous transluminal angioplasty vs medical therapy in hypertensive patients with both unilateral and bilateral disease. Methods: A total of 135 eligible patients were identified, of whom 55 (44%) were randomised. Eligible patients had sustained hypertension, with a minimum diastolic BP of 95 mm Hg on at least two anti-hypertensive drugs. Renal artery stenosis was defined by renal angiography as at least 50% stenosis in the affected vessel. All patients were observed during an initial 4-week run-in period on a fixed drug regimen and subsequent changes measured from this 4-week baseline. Results: Blood pressure fell during the run-in period in all groups. In patients with bilateral renal artery stenosis randomised to angioplasty, a statistically significant (P < 0.05) fall in bp was observed at latest follow-up (range 3–54 months). the mean fall in bp at latest follow- up in the angioplasty group, corrected for the medical group response, was 26/10 mm hg. in patients with unilateral renal artery stenosis, no statistically significant or clinically important differences in outcome were observed between the two groups. no significant differences or trends in serum creatinine were observed between or within any group during follow-up. major outcome events (death, myocardial infarction, heart failure, stroke, dialysis) were similar in the angioplasty and medical groups during follow-up. in the 40/135 patients undergoing angioplasty, serious or potentially serious complications attributable to the procedure were observed in 11 patients, bleeding at the arterial site (8 patients) being the most frequent. Conclusions: In hypertensive patients with atheromatous renal artery stenosis, percutaneous renal angioplasty results in a modest improvement in systolic BP compared with medical therapy alone. This benefit was confined to patients with bilateral disease. No patient was ‘cured’, renal function did not improve, and intervention was accompanied by a significant complication rate.

2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension.

1. INTRODUCTION1.1 PrinciplesThe 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext

Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus

TREX1 acts in concert with the SET complex in granzyme A–mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3′ UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 × 10−7). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE.

Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2×10−201), ABCG2 (p = 3.1×10−26), SLC17A1 (p = 3.0×10−14), SLC22A11 (p = 6.7×10−14), SLC22A12 (p = 2.0×10−9), SLC16A9 (p = 1.1×10−8), GCKR (p = 1.4×10−9), LRRC16A (p = 8.5×10−9), and near PDZK1 (p = 2.7×10−9). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0×10−26) and propionyl-L-carnitine (p = 5.0×10−8) concentrations, which in turn were associated with serum UA levels (p = 1.4×10−57 and p = 8.1×10−54, respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.

Effect of renal-artery stenting on progression of renovascular renal failure

BACKGROUND Placement of renal-artery stents has a high technical success rate in atherosclerotic renovascular disease, but little is known about the clinical benefits of the procedure. We monitored renal function serially before and after stent insertion in patients with renovascular renal failure. METHODS Renal function was assessed before and after stent placement by means of serial serum creatinine values in 32 patients with atherosclerotic renal-artery stenosis. The effect on the progression of renal failure was analysed in 23 patients by comparison of the reciprocal slopes of serum creatinine versus time plots before and after stent placement. FINDINGS 33 transluminal stents were placed in 32 patients with atherosclerotic renovascular disease. Immediate patency was achieved in all cases: the angiographic restenosis rate at 6 months was 12% (n = 24). One patient died after a procedure-related haemorrhage. Median diastolic blood pressure was significantly lower after stenting than before (95 [IQR 86-103] vs 87 [81-90] mm Hg; p > 0.01) but the requirement for antihypertensive drugs was unchanged. Renal function improved or stabilised in 22 (69%) of the 32 patients. Progression of renal failure was significantly slowed after the procedure; the mean (SE) of the slopes of reciprocal serum creatinine values was -4.34 (0.85) L mumol-1 day-1 before stent placement, and -0.55 (1.0) L mumol-1 day-1 after stent placement (p < 0.01, two-sample t test). INTERPRETATION Renal-stent placement in selected patients slows the progression of renovascular renal failure and may delay the need for renal replacement therapy.

Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia.

Many common diseases are accompanied by disturbances in biochemical traits. Identifying the genetic determinants could provide novel insights into disease mechanisms and reveal avenues for developing new therapies. Here, we report a genome-wide association analysis for commonly measured serum and urine biochemical traits. As part of the WTCCC, 500,000 SNPs genome wide were genotyped in 1955 hypertensive individuals characterized for 25 serum and urine biochemical traits. For each trait, we assessed association with individual SNPs, adjusting for age, sex, and BMI. Lipid measurements were further examined in a meta-analysis of genome-wide data from a type 2 diabetes scan. The most promising associations were examined in two epidemiological cohorts. We discovered association between serum urate and SLC2A9, a glucose transporter (p = 2 x 10(-15)) and confirmed this in two independent cohorts, GRAPHIC study (p = 9 x 10(-15)) and TwinsUK (p = 8 x 10(-19)). The odds ratio for hyperuricaemia (defined as urate >0.4 mMol/l) is 1.89 (95% CI = 1.36-2.61) per copy of common allele. We also replicated many genes previously associated with serum lipids and found previously recognized association between LDL levels and SNPs close to genes encoding PSRC1 and CELSR2 (p = 1 x 10(-7)). The common allele was associated with a 6% increase in nonfasting serum LDL. This region showed increased association in the meta-analysis (p = 4 x 10(-14)). This finding provides a potential biological mechanism for the recent association of this same allele of the same SNP with increased risk of coronary disease.

Superoxide Anion Production Is Increased in a Model of Genetic Hypertension: Role of the Endothelium

The hypothesis that the decreased nitric oxide (NO) availability observed in spontaneously hypertensive stroke-prone rats (SHRSP) is due to excess superoxide (O2-) was examined. O2- generation, measured by lucigenin chemiluminescence, was studied in 12- to 16-week male and female Wistar-Kyoto rats (WKY) and SHRSP. In addition, expression of the gene encoding endothelial NO synthase, the enzyme involved in NO generation, was investigated. O2- generation was increased in male and female SHRSP (4.11+/-0.24 and 3. 84+/-0.28 nmol O2-. min-1. mg-1 respectively) compared with their WKY counterparts and was significantly higher in male than female WKY (1.22+/-0.08 in males and 0.8+/-0.08 nmol O2-. min-1. mg-1 respectively) (SHRSP versus WKY P<0.0001, 95% CI -3.39, -2.51; male versus female WKY P=0.0029, 95% CI -0.67, -0.17). Removal of the endothelium by rubbing or addition of NO synthase inhibitors attenuated O2- generation in SHRSP but not WKY. In males, removal of the endothelium reduced O2- generation from 3.86+/-0.12 to 1.35+/-0. 08 nmol. min-1. mg-1 (P<0.0001, 95% CI 2.29, 2.81), whereas addition of L-NAME caused a reduction from 4.13+/-0.17 to 1.32+/-0.16 nmol. min-1. mg-1 (P<0.0001, 95% CI 2.36, 2.83). Similar reductions were observed in females. L-arginine had no significant effect, but tetrahydrobiopterin significantly decreased O2- generation in SHRSP from 4.04+/-0.11 to 2.36+/-0.40 nmol. min-1. mg-1 (P=0.0026, 95% CI 0.89, 2.44). Endothelial NO synthase mRNA expression was significantly greater in SHRSP than in WKY and in WKY males than in WKY females. These results show that O2- generation is increased in SHRSP and that the tissue and enzymatic sources of this excess O2- appear to be the endothelium and eNOS, respectively. The increase in O2- generation could explain the decreased availability of basal NO observed in this model of genetic hypertension.