Clinical and Genetic Determinants of Varicose Veins.

Abstract:

BACKGROUND:Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. METHODS:We applied machine learning to agnostically search for risk factors of varicose veins in 493 519 individuals in the UK Biobank. Predictors were further studied with univariable and multivariable Cox regression analyses (2441 incident events). A genome-wide association study of varicose veins was also performed among 337 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. RESULTS:Machine learning confirmed several known (age, sex, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease, including height. After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins (hazard ratio for upper versus lower quartile, 1.74; 95% CI, 1.51-2.01; P<0.0001). A genome-wide association study identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (inverse-variance weighted: odds ratio, 1.26; P=2.07×10-16). CONCLUSIONS:Using data from nearly a half-million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.

journal_name

Circulation

journal_title

Circulation

authors

Fukaya E,Flores AM,Lindholm D,Gustafsson S,Zanetti D,Ingelsson E,Leeper NJ

doi

10.1161/CIRCULATIONAHA.118.035584

keywords:

["epidemiology","genetics","genome-wide association study","varicose veins"]

subject

Has Abstract

pub_date

2018-12-18 00:00:00

pages

2869-2880

issue

25

eissn

0009-7322

issn

1524-4539

journal_volume

138

pub_type

杂志文章,多中心研究
  • Availability and Use of Shared Data From Cardiometabolic Clinical Trials.

    abstract:BACKGROUND:Sharing of patient-level clinical trial data has been widely endorsed. Little is known about how extensively these data have been used for cardiometabolic diseases. We sought to evaluate the availability and use of shared data from cardiometabolic clinical trials. METHODS:We extracted data from ClinicalStud...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.117.031883

    authors: Vaduganathan M,Nagarur A,Qamar A,Patel RB,Navar AM,Peterson ED,Bhatt DL,Fonarow GC,Yancy CW,Butler J

    更新日期:2018-02-27 00:00:00

  • Ultrasonic tissue characterization of human hypertrophied hearts in vivo with cardiac cycle-dependent variation in integrated backscatter.

    abstract::Integrated ultrasonic backscatter (IB) is a noninvasive measure of the acoustic properties of myocardium. Previous experimental studies have indicated that altered acoustic properties of the myocardium are reflected by the magnitude of variation of IB during the cardiac cycle. In our study, cardiac cycle-dependent var...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.80.4.925

    authors: Masuyama T,St Goar FG,Tye TL,Oppenheim G,Schnittger I,Popp RL

    更新日期:1989-10-01 00:00:00

  • Influence of mitral valve surgery on tricuspid incompetence concomitant with mitral valve disease.

    abstract::Twenty adult patients with predominant mitral valve disease and variable degrees of tricuspid incompetence (TI) were reinvestigated 6-28 months after mitral valve operation. Postoperatively, 10 of the 20 patients were in sinus rhythm, compared with four of 20 preoperatively. Right ventricula peak systolic pressure dec...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:

    authors: Simon R,Oelert H,Borst HG,Lichtlen PR

    更新日期:1980-08-01 00:00:00

  • Physical activity and coronary heart disease in men: The Harvard Alumni Health Study.

    abstract:BACKGROUND:The quantity and intensity of physical activity required for the primary prevention of coronary heart disease (CHD) remain unclear. Therefore, we examined the association of the quantity and intensity of physical activity with CHD risk and the impact of other coronary risk factors. METHODS AND RESULTS:We fo...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.102.9.975

    authors: Sesso HD,Paffenbarger RS Jr,Lee IM

    更新日期:2000-08-29 00:00:00

  • Factors influencing the success of ventricular defibrillation in man.

    abstract::To define the factors influencing the success of emergency ventricular defibrillation, we identified 52 patients defibrillated at the University of Iowa Hospital during 1974--1976. Thirty-eight patients were successfully defibrillated at least once; 14 could not be defibrillated, despite multiple attempts. Comparisons...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.60.2.226

    authors: Kerber RE,Sarnat W

    更新日期:1979-08-01 00:00:00

  • Effects of lower-body negative pressure on sympathetic nerve responses to static exercise in humans. Microneurographic evidence against cardiac baroreflex modulation of the exercise pressor reflex.

    abstract::Although previous studies in both animals and humans have suggested that cardiac baroreceptors modulate reflex sympathetic vasoconstriction during exercise, more recent studies in conscious animals have not supported this view. To further test this concept in humans, we measured sympathetic nerve discharge with intran...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.78.1.49

    authors: Scherrer U,Vissing SF,Victor RG

    更新日期:1988-07-01 00:00:00

  • Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischemia.

    abstract:BACKGROUND:The release of endothelium-derived relaxing factors has been shown experimentally to be of pivotal importance for the maintenance of coronary blood flow during increased demand. In humans with coronary atherosclerosis, endothelial vasodilator dysfunction is not confined only to epicardial conductance vessels...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.91.9.2345

    authors: Zeiher AM,Krause T,Schächinger V,Minners J,Moser E

    更新日期:1995-05-01 00:00:00

  • Dietary fat intake determines the effect of a common polymorphism in the hepatic lipase gene promoter on high-density lipoprotein metabolism: evidence of a strong dose effect in this gene-nutrient interaction in the Framingham Study.

    abstract:BACKGROUND:Gene-nutrient interactions affecting high-density lipoprotein cholesterol (HDL-C) concentrations may contribute to the interindividual variability of the cardiovascular disease risk associated with dietary fat intake. Hepatic lipase (HL) is a key determinant of HDL metabolism. Four polymorphisms in linkage d...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.0000036597.52291.c9

    authors: Ordovas JM,Corella D,Demissie S,Cupples LA,Couture P,Coltell O,Wilson PW,Schaefer EJ,Tucker KL

    更新日期:2002-10-29 00:00:00

  • Thyroid hormone coordinates respiratory control maturation and adenine nucleotide translocator expression in heart in vivo.

    abstract:BACKGROUND:The signal transduction mechanism linking mitochondrial ATP synthesis with cytosolic ATP utilization in heart changes during postnatal development in vivo. This maturational process occurs in parallel with accumulation of mitochondrial adenine nucleotide translocator (ANT), which provides a possible site for...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.102.11.1323

    authors: Portman MA,Xiao Y,Qian K,Tucker RL,Parish SM,Ning XH

    更新日期:2000-09-12 00:00:00

  • Distribution of extracellular potassium and its relation to electrophysiologic changes during acute myocardial ischemia in the isolated perfused porcine heart.

    abstract::An experimental approach is described to quantitate inhomogeneity in extracellular K concentration ([K+]out) in the presence of ischemia and to relate this inhomogeneity to the electrophysiologic changes. Extracellular potassium concentration and local direct-current electrograms from the same sites were measured in i...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.77.5.1125

    authors: Coronel R,Fiolet JW,Wilms-Schopman FJ,Schaapherder AF,Johnson TA,Gettes LS,Janse MJ

    更新日期:1988-05-01 00:00:00

  • Height and incidence of cardiovascular disease in male physicians.

    abstract:BACKGROUND:An inverse association between height and risk of coronary heart disease (CHD) has been reported in several case-control and cohort studies, but the reasons for the association remain uncertain. We evaluated this association among 22,071 male physicians, a population homogeneous for high educational attainme...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1161/01.cir.88.4.1437

    authors: Hebert PR,Rich-Edwards JW,Manson JE,Ridker PM,Cook NR,O'Connor GT,Buring JE,Hennekens CH

    更新日期:1993-10-01 00:00:00

  • Improving blood pressure control through a clinical pharmacist outreach program in patients with diabetes mellitus in 2 high-performing health systems: the adherence and intensification of medications cluster randomized, controlled pragmatic trial.

    abstract:BACKGROUND:Even in high-performing health systems, some patients with diabetes mellitus have poor blood pressure (BP) control because of poor medication adherence and lack of medication intensification. We examined whether the Adherence and Intensification of Medications intervention, a pharmacist-led intervention comb...

    journal_title:Circulation

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1161/CIRCULATIONAHA.111.089169

    authors: Heisler M,Hofer TP,Schmittdiel JA,Selby JV,Klamerus ML,Bosworth HB,Bermann M,Kerr EA

    更新日期:2012-06-12 00:00:00

  • Long-term use of nicotine gum is associated with hyperinsulinemia and insulin resistance.

    abstract:BACKGROUND:Insulin sensitivity and cardiovascular risk profile were examined in 20 healthy, nonobese, middle-aged men who were long-term users of nicotine-containing chewing gum and in 20 matched control subjects who did not use nicotine. METHODS AND RESULTS:Long-term use of nicotine-containing chewing gum was associa...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.94.5.878

    authors: Eliasson B,Taskinen MR,Smith U

    更新日期:1996-09-01 00:00:00

  • Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts.

    abstract:BACKGROUND:Ranolazine is a novel antianginal agent that may reduce symptoms without affecting hemodynamics and has shown cardiac antiischemic effects in in vivo and in vitro models. In one study it increased active pyruvate dehydrogenase (PDHa). Other agents that increase PDHa and so increase glucose and decrease fatty...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.93.1.135

    authors: McCormack JG,Barr RL,Wolff AA,Lopaschuk GD

    更新日期:1996-01-01 00:00:00

  • Influence of racial disparities in procedure use on functional status outcomes among patients with coronary artery disease.

    abstract:BACKGROUND:Although black cardiac patients receive fewer revascularization procedures than whites, it is unclear whether this has a detrimental impact on outcomes. The objective of our study was to compare 6-month functional status and angina outcomes among blacks and whites with documented coronary disease and to asse...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000157731.66268.E1

    authors: Kaul P,Lytle BL,Spertus JA,DeLong ER,Peterson ED

    更新日期:2005-03-15 00:00:00

  • Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study.

    abstract:BACKGROUND:Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in pati...

    journal_title:Circulation

    pub_type: 杂志文章,随机对照试验

    doi:10.1161/CIRCULATIONAHA.113.001458

    authors: Bonderman D,Ghio S,Felix SB,Ghofrani HA,Michelakis E,Mitrovic V,Oudiz RJ,Boateng F,Scalise AV,Roessig L,Semigran MJ,Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial (LEPHT) Study Group.

    更新日期:2013-07-30 00:00:00

  • Adenylylcyclase increases responsiveness to catecholamine stimulation in transgenic mice.

    abstract:BACKGROUND:The cellular content of cAMP generated by activation of adenylylcyclase (AC) through the beta-adrenergic receptor (betaAR) is a key determinant of a cell's response to catecholamine stimulation. We tested the hypothesis that increased AC content, independently of betaAR number, increases responsiveness to ca...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.99.12.1618

    authors: Gao MH,Lai NC,Roth DM,Zhou J,Zhu J,Anzai T,Dalton N,Hammond HK

    更新日期:1999-03-30 00:00:00

  • Overexpression of thioredoxin-1 in transgenic mice attenuates adriamycin-induced cardiotoxicity.

    abstract:BACKGROUND:Adriamycin (ADR) is an anticancer drug known to cause severe cardiac toxicity by generating free radicals. We investigated the role of a redox-regulating molecule, thioredoxin-1 (TRX1), in ADR-induced cardiotoxicity. METHODS AND RESULTS:The in vitro study showed that TRX1 was dose-dependently increased conc...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.0000027817.55925.b4

    authors: Shioji K,Kishimoto C,Nakamura H,Masutani H,Yuan Z,Oka S,Yodoi J

    更新日期:2002-09-10 00:00:00

  • Activation patterns of Purkinje fibers during long-duration ventricular fibrillation in an isolated canine heart model.

    abstract:BACKGROUND:The roles of Purkinje fibers (PFs) and focal wave fronts, if any, in the maintenance of ventricular fibrillation (VF) are unknown. If PFs are involved in VF maintenance, it should be possible to map wave fronts propagating from PFs into the working ventricular myocardium during VF. If wave fronts ever arise ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.107.699264

    authors: Tabereaux PB,Walcott GP,Rogers JM,Kim J,Dosdall DJ,Robertson PG,Killingsworth CR,Smith WM,Ideker RE

    更新日期:2007-09-04 00:00:00

  • Hemodynamic evaluation of the heart with a nonfluoroscopic electromechanical mapping technique.

    abstract:BACKGROUND:Clinical cardiac volumetric measurement techniques are essential for assessing cardiac performance but produce significant inaccuracies in extrapolation of the volume of a three-dimensional (3D) object from two-dimensional images and lack the ability to associate cardiac electrical and mechanical activities....

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.96.10.3672

    authors: Gepstein L,Hayam G,Shpun S,Ben-Haim SA

    更新日期:1997-11-18 00:00:00

  • Relation between mild renal dysfunction and outcomes after coronary artery bypass grafting.

    abstract:BACKGROUND:Risk stratification algorithms for coronary artery bypass grafting (CABG) do not include a weighting for preoperative mild renal impairment defined as a serum creatinine 130 to 199 micromol/L (1.47 to 2.25 mg/dL), which may impact mortality and morbidity after CABG. METHODS AND RESULTS:We reviewed prospecti...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.104.522623

    authors: Zakeri R,Freemantle N,Barnett V,Lipkin GW,Bonser RS,Graham TR,Rooney SJ,Wilson IC,Cramb R,Keogh BE,Pagano D

    更新日期:2005-08-30 00:00:00

  • Digitalis and the sick sinus syndrome. Clinical and electrophysiologic documentation of severe toxic effect on sinus node function.

    abstract::Digoxin, in a common clinical dose and at a low serum level, brought out severe manifestations of sinus node dysfunction in a patient who had previously undergone successful mitral valve replacement. This report presents the results of extensive clinical and electrophysiologic studies of this patient before and after ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.52.1.162

    authors: Margolis JR,Strauss HC,Miller HC,Gilbert M,Wallace AG

    更新日期:1975-07-01 00:00:00

  • Mechanism of ST elevation and ventricular arrhythmias in an experimental Brugada syndrome model.

    abstract:BACKGROUND:Although phase 2 reentry is said to be responsible for initiation of ventricular tachycardia (VT) in Brugada syndrome, information about the activation sequence during VT is limited. METHODS AND RESULTS:We developed an experimental Brugada syndrome model using a canine isolated right ventricular preparation...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000105762.94855.46

    authors: Kimura M,Kobayashi T,Owada S,Ashikaga K,Higuma T,Sasaki S,Iwasa A,Motomura S,Okumura K

    更新日期:2004-01-06 00:00:00

  • Detection of injury-induced vascular remodeling by targeting activated alphavbeta3 integrin in vivo.

    abstract:BACKGROUND:The alpha(v)beta3 integrin plays a critical role in cell proliferation and migration. We hypothesized that vascular cell proliferation, a hallmark of injury-induced remodeling, can be tracked by targeting alpha(v)beta3 integrin expression in vivo. METHODS AND RESULTS:RP748, a novel 111In-labeled alpha(v)bet...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000133319.84326.70

    authors: Sadeghi MM,Krassilnikova S,Zhang J,Gharaei AA,Fassaei HR,Esmailzadeh L,Kooshkabadi A,Edwards S,Yalamanchili P,Harris TD,Sinusas AJ,Zaret BL,Bender JR

    更新日期:2004-07-06 00:00:00

  • Cardiac interbeat interval dynamics from childhood to senescence : comparison of conventional and new measures based on fractals and chaos theory.

    abstract:BACKGROUND:New methods of R-R interval variability based on fractal scaling and nonlinear dynamics ("chaos theory") may give new insights into heart rate dynamics. The aims of this study were to (1) systematically characterize and quantify the effects of aging from early childhood to advanced age on 24-hour heart rate ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.100.4.393

    authors: Pikkujämsä SM,Mäkikallio TH,Sourander LB,Räihä IJ,Puukka P,Skyttä J,Peng CK,Goldberger AL,Huikuri HV

    更新日期:1999-07-27 00:00:00

  • Extensive primary repair of the thoracic aorta in acute type a aortic dissection by means of ascending aorta replacement combined with open placement of triple-branched stent graft: early results.

    abstract:BACKGROUND:To simplify extensive primary repair of the thoracic aorta in acute type A aortic dissection, we developed the open triple-branched stent graft placement technique. The early results of this new technique are reported. METHODS AND RESULTS:Between June 2008 and November 2009, 30 patients with acute Stanford ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.110.946012

    authors: Chen LW,Dai XF,Lu L,Zhang GC,Cao H

    更新日期:2010-10-05 00:00:00

  • Complete isolation of left atrium surrounding the pulmonary veins: new insights from the double-Lasso technique in paroxysmal atrial fibrillation.

    abstract:BACKGROUND:Paroxysmal atrial fibrillation (PAF) can be eliminated with continuous circular lesions (CCLs) around the pulmonary veins (PVs), but it is unclear whether all PVs are completely isolated. METHODS AND RESULTS:Forty-one patients with symptomatic PAF underwent 3D mapping, and all PV ostia were marked on the 3D...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000144459.37455.EE

    authors: Ouyang F,Bänsch D,Ernst S,Schaumann A,Hachiya H,Chen M,Chun J,Falk P,Khanedani A,Antz M,Kuck KH

    更新日期:2004-10-12 00:00:00

  • Adenosine alters glucose use during ischemia and reperfusion in isolated rat hearts.

    abstract:BACKGROUND:Adenosine possesses marked cardioprotective properties, but the mechanisms for this beneficial effect are unclear. The objective of this study was to determine the effect of adenosine given before ischemia or at reperfusion on mechanical function, glucose oxidation, glycolysis, and metabolite levels in isola...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.87.3.900

    authors: Finegan BA,Lopaschuk GD,Coulson CS,Clanachan AS

    更新日期:1993-03-01 00:00:00

  • Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation.

    abstract:BACKGROUND:Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.103.5.684

    authors: Brundel BJ,Van Gelder IC,Henning RH,Tieleman RG,Tuinenburg AE,Wietses M,Grandjean JG,Van Gilst WH,Crijns HJ

    更新日期:2001-02-06 00:00:00

  • Weight-loss-associated induction of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice.

    abstract:BACKGROUND:Weight loss in obese insulin-resistant but not in insulin-sensitive persons reduces coronary heart disease risk. To what extent changes in gene expression are related to atherosclerosis and cardiovascular function is unknown. METHODS AND RESULTS:We studied the effect of diet restriction-induced weight loss ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000147614.85888.7A

    authors: Verreth W,De Keyzer D,Pelat M,Verhamme P,Ganame J,Bielicki JK,Mertens A,Quarck R,Benhabilès N,Marguerie G,Mackness B,Mackness M,Ninio E,Herregods MC,Balligand JL,Holvoet P

    更新日期:2004-11-16 00:00:00