Abstract:
BACKGROUND:C-reactive protein (CRP) both reflects and participates in inflammation, and its circulating concentration marks cardiovascular risk. Here we sought to understand the role of heredity in determining CRP secretion. METHODS:CRP, as well as multiple facets of the metabolic syndrome, were measured in a series of 229 twins, both monozygotic (MZ) and dizygotic (DZ), to estimate trait heritability (h2). Single nucleotide polymorphism (SNP) genotyping was done at adrenergic pathway loci. Haplotypes were inferred from genotypes by likelihood methods. Association of CRP with hypertension and the metabolic syndrome was studied in a larger series of 732 individuals, including 79 with hypertension. RESULTS:MZ and DZ twin variance components indicated substantial h2 for CRP, at approximately 56 +/- 7% (P < 0.001). CRP was significantly associated (P < 0.05) with multiple features of the metabolic syndrome in twins, including body mass index (BMI), blood pressure (BP), leptin and lipids. In established hypertension, elevated CRP was associated with increased BP, BMI, insulin, HOMA (index of insulin resistance), leptin, triglycerides and norepinephrine. Twin correlations indicated pleiotropy (shared genetic determination) for CRP with BMI (P = 0.0002), leptin (P < 0.001), triglycerides (P = 0.002) and systolic blood pressure (SBP) (P = 0.042). Approximately 9800 genotypes (43 genetic variants at 17 loci) were scored within catecholaminergic pathways: biosynthetic, receptor and signal transduction. Plasma CRP concentration in twins was predicted by polymorphisms at three loci in physiological series within the catecholamine biosynthetic/beta-adrenergic pathway: TH (tyrosine hydroxylase), ADRB1 (beta1-adrenergic receptor) and ADRB2 (beta2-adrenergic receptor). In the TH promoter, common allelic variation accounted for up to approximately 6.6% of CRP inter-individual variance. At ADRB1, variation at Gly389Arg predicted approximately 2.8% of CRP, while ADRB2 promoter variants T-47C and T-20C also contributed. Particular haplotypes and diplotypes at TH and ADRB1 also predicted CRP, though typically no better than single SNPs alone. Epistasis (gene-by-gene interaction) was demonstrated for particular combinations of TH and ADRB2 alleles, consistent with their actions in a pathway in series. In an illustration of pleiotropy, not only CRP but also plasma triglycerides were predicted by polymorphisms at TH (P = 0.0053) and ADRB2 (P = 0.027). CONCLUSIONS:CRP secretion is substantially heritable in humans, demonstrating pleiotropy (shared genetic determination) with other features of the metabolic syndrome, such as BMI, triglycerides or BP. Multiple, common genetic variants in the catecholaminergic/beta-adrenergic pathway contribute to CRP, and these variants (especially at TH and ADRB2) seem to interact (epistasis) to influence the trait. The results uncover novel pathophysiological links between the adrenergic system and inflammation, and suggest new strategies to probe the role and actions of inflammation within this setting.
journal_name
J Hypertensjournal_title
Journal of hypertensionauthors
Wessel J,Moratorio G,Rao F,Mahata M,Zhang L,Greene W,Rana BK,Kennedy BP,Khandrika S,Huang P,Lillie EO,Shih PA,Smith DW,Wen G,Hamilton BA,Ziegler MG,Witztum JL,Schork NJ,Schmid-Schönbein GW,O'Connor DTdoi
10.1097/HJH.0b013e328011753esubject
Has Abstractpub_date
2007-02-01 00:00:00pages
329-43issue
2eissn
0263-6352issn
1473-5598pii
00004872-200702000-00013journal_volume
25pub_type
杂志文章abstract:OBJECTIVE:To clarify the spectrum of the left ventricular responses in hypertension in man by means of coupled analysis of elastances. In the present study we analysed the 'functional' coupling of the left ventricle and the arterial system in terms of the arterial effective elastance (E(a)) divided by a value of end-sy...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract:OBJECTIVES:We aimed to determine the association of nonalcoholic fatty liver disease (NAFLD) with central and peripheral blood pressure (BP), in a general adolescent population and to examine whether associations are independent of adiposity. METHODS:Using cross-sectional data from a subsample (N = 1904) of a UK birth...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000445
更新日期:2015-03-01 00:00:00
abstract::Noradrenergic activity was measured in the brainstem, hypothalamus and thoracic spinal cord of male and female spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 6 and 28-36 weeks of age. Two techniques were used, measurement of a major noradrenaline (NA) metabolite, free 3,4-dihydroxyphenylethyleneglycol...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198506000-00007
更新日期:1985-06-01 00:00:00
abstract:BACKGROUND:Angiotensin II causes hypertension not only by direct constriction of vascular smooth muscle, but also by facilitating the release of noradrenaline from sympathetic terminals and by enhancing vascular noradrenaline sensitivity. AT1 receptor antagonists attenuate all these actions, but display some evidence o...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000179510.86265.63
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVE:The objective of the study was to investigate interarm differences of blood pressure (BP) and its determinants, and to clarify whether both arms are equally good in assessing BP and target organ damage in the general population. METHODS:We studied a representative sample of Finnish adult population with 484 ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000040
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:Work stress contributes to risk of coronary heart disease and hypertension. This study tested the influence of job control on ambulatory blood pressure, and ratings of perceived stress and happiness in men and women systematically sampled by socio-economic status from the Whitehall II epidemiological cohort. ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200405000-00012
更新日期:2004-05-01 00:00:00
abstract:OBJECTIVE:Ethnic minority populations (EMPs) are disproportionally affected by hypertension-mediated complications compared with European host populations (EHPs), which might be due to disparities in hypertension awareness, treatment and control. We conducted a systematic review and meta-analysis to compare awareness, ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002651
更新日期:2021-02-01 00:00:00
abstract::Plasma atrial natriuretic peptide (ANP) concentrations were measured by both direct radio-immunoassay and with pre-extraction of the peptide from plasma using C18 reverse phase columns. Peptide concentrations were measured in normal subjects (including a group of eight volunteers who received an intravenous infusion o...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198704000-00015
更新日期:1987-04-01 00:00:00
abstract:OBJECTIVE:Gap junctions, formed by connexins (Cx), are important in the regulation of vascular tone. Previously, we reported two closely linked polymorphisms (-44G --> A and +71A --> G) within regulatory regions of the gene for Cx40, a major connexin in the vascular wall and the kidney. In the present study, we examine...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000200512.40818.47
更新日期:2006-02-01 00:00:00
abstract:OBJECTIVE:We investigated the impact of renal function on outcomes after percutaneous transluminal angioplasty. METHODS:A total of 139 hypertensive patients with atherosclerotic renal artery stenosis (mean age, 70 years, 80.6% men) who underwent renal percutaneous transluminal angioplasty were included. Renal function...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001499
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVES:Some beta-blockers are less effective in reducing central blood pressure than other antihypertensive drugs, which may explain the higher rate of events in subjects randomized to atenolol in recent trials. We hypothesized that nebivolol, a mixed beta-blocker/nitro-vasodilator, would be more effective than ate...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e3282f283c9
更新日期:2008-02-01 00:00:00
abstract::Seventeen essential hypertensive patients with normal renal function were treated with a new non-sulphydryl orally active angiotensin converting enzyme (ACE) inhibitor, benazepril, 10 mg given once or twice daily, according to diastolic blood pressure levels, for 6 weeks. In all patients, changes in blood pressure, sy...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199011000-00003
更新日期:1990-11-01 00:00:00
abstract:OBJECTIVE:Some cases of pseudopheochromocytoma have been described among hypertensive patients with obstructive sleep apnea (OSA). This study examined whether a pathological rise of urinary metanephrines is a common feature in hypertensive OSA patients and, in such a case, whether the ventilation treatment during sleep...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001507
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVES:The role of the baroreflex function in the pathogenesis of hemodialysis-associated hypotension is controversial. Complex demodulation technique (CDM), providing continuous assessment of the amplitude of cardiovascular oscillation over time, is particularly suitable to assess dynamic changes in autonomic nerv...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328332b7af
更新日期:2010-02-01 00:00:00
abstract:OBJECTIVE:The mechanisms underlying the relationship between the vascular complications of diabetes and the glycaemic control are not well understood. We tested whether glycaemic control influences the functioning of the nitric oxide system in type 1 diabetic patients and the role for oxidative stress. METHODS:The cha...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/00004872-200306000-00013
更新日期:2003-06-01 00:00:00
abstract:OBJECTIVE:This study was designed to compare the effects of prostaglandin synthesis inhibition on calculated preglomerular and postglomerular resistance in hypertensive patients with unilateral renal artery stenosis (RAS) and in patients with essential hypertension. DESIGN AND METHODS:Sixteen patients with suspected r...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/00004872-199606000-00013
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND:The effects of aspirin in subjects without cardiovascular disease are controversial. In the intensively treated patients of the Hypertension Optimal Treatment (HOT) Study, randomization to low-dose aspirin (75 mg daily) versus placebo significantly reduced cardiovascular events (-15%) and myocardial infarcti...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004872-200211000-00031
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVES:The goal of this study was to compare the cardiovascular responses to behavioural stressors of three groups of adolescents who differed in blood pressure status across assessments. DESIGN:Casual blood pressure of adolescents who were identified as having elevated blood pressure during a school screen was re...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200101000-00003
更新日期:2001-01-01 00:00:00
abstract::The concentrations of neuropeptide Y immunoreactivity (NPY-ir) were measured in the cortex and cervical, thoracic and lumbar spinal cord of 8-, 18- and 31-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). This peptide was measured using a highly sensitive and specific radio-immun...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198608000-00012
更新日期:1986-08-01 00:00:00
abstract:OBJECTIVE:To characterize the in vivo vascular properties of the spontaneously hypertensive rat (SHR) renal vascular bed by examining vascular conductance/resistance responsiveness to vasoactive agents in vivo and determining whether the filtration surface area of glomerular capillaries is reduced. DESIGN AND METHODS:...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200108000-00020
更新日期:2001-08-01 00:00:00
abstract:OBJECTIVE:To determine whether the decision to treat uncomplicated mild hypertension with drugs, in accordance with the World Health Organization - International Society of Hypertension (WHO/ISH) guidelines based on a series of blood pressure (BP) measurements over 6 months, resulted in the treatment of patients at hig...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199917060-00014
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:International recommendations have classified brachial blood pressure (BP) in subgroups enabling better cardiovascular risk stratification. Central BP is an independent predictor of cardiovascular risk, differing from brachial BP through the predominant influence of arterial stiffness and wave reflections. C...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3282f16a9c
更新日期:2008-01-01 00:00:00
abstract::Microvascular alterations associated with reversal of hypertension by exposure to simulated high altitude were investigated in the gracilis muscle of the spontaneously hypertensive rat (SHR). Male, 4-week-old SHR were either placed in a hypobaric chamber (SHR-HA) at 430 mmHg or maintained at ambient barometric pressur...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198612000-00008
更新日期:1986-12-01 00:00:00
abstract:OBJECTIVES:Genetic variants that influence large conductance calcium-activated potassium channel's function may alter arterial function and contribute to the known heritability of arterial stiffness and blood pressure. The beta1-subunit (KCNMB1) of the large conductance calcium-activated potassium channel includes two ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328317c8ae
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVE:To compare the effects of the angiotensin II receptor antagonist candesartan with the angiotensin-converting enzyme inhibitor enalapril on myocardial fibrosis evaluated by echoreflectivity analysis. METHODS:Hypertensive patients (n = 196) with echocardigraphically documented left ventricular hypertrophy were...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e3283232838
更新日期:2009-03-01 00:00:00
abstract:OBJECTIVE:We have recently shown that mean pulse pressure is higher in patients with transient myocardial ischemia. Pulse pressure elevation might be an important consequence of increased arterial stiffness. The aim of this study was to prove if arterial stiffness is changed in patients with transient myocardial ischem...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000244959.92856.7e
更新日期:2006-10-01 00:00:00
abstract:OBJECTIVES:The rostral ventrolateral medulla (RVLM) of the brainstem and the paraventricular nucleus (PVN) of the hypothalamus play crucial roles in central cardiovascular regulation. In hypertensive rats, an imbalance of excitatory and inhibitory inputs to the RVLM enhances central sympathetic outflow. Increased react...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32834e1df4
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:The use of thiazide diuretics in the treatment of hypertension is widely considered as a first-line treatment, given the efficacy and low cost of this class of drugs. This indication is not unanimous, because thiazides can cause metabolic alterations, and other side effects that reduce compliance and persist...
journal_title:Journal of hypertension
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/HJH.0b013e328353398b
更新日期:2012-06-01 00:00:00
abstract:OBJECTIVES:To test whether the Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene is of functional relevance in humans by altering endothelium-dependent vasodilation. BACKGROUND:The Asp298 variant of the eNOS gene product has been associated with arterial hypertension, coronary artery disease ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200018120-00010
更新日期:2000-12-01 00:00:00
abstract::The relationships between five erythrocyte cation transport systems (Na(+)-K+ pump, Na(+)-K+ cotransport, Na(+)-Li+ countertransport and Na+ and K+ passive permeabilities) and plasma lipids (total plasma cholesterol, high-density lipoprotein cholesterol and triglycerides) were investigated in 129 male adult subjects w...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199010000-00002
更新日期:1990-10-01 00:00:00