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Association of the C-Reactive Protein Gene (CRP) rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis.

ABSTRACT: Elevation in C-reactive protein (CRP) levels have been shown in patients with aortic valve stenosis (AS). Minor allele of the CRP gene (CRP) rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for the rs1205 C>T polymorphism using the TaqMan assay. Severity of the AS was assessed using transthoracic echocardiography. The degree of calcification was analyzed semi-quantitatively. Carriers of the rs1205 T allele were characterized by elevated serum CRP levels (2.53 (1.51-3.96) vs. 1.68 (0.98-2.90) mg/L, p<0.001) and a higher proportion of the severe aortic valve calcification (70.4% vs. 55.1%, p=0.01) compared with major homozygotes. The effect of CRP rs1205 polymorphism on CRP levels is opposite in AS-affected than in unaffected subjects, suggesting existence of a disease-specific molecular regulatory mechanism. Furthermore, rs1205 variant allele predisposes to larger aortic valve calcification, potentially being a novel genetic risk marker of disease progression.

SUBMITTER: Wypasek E

PROVIDER: S-EPMC4632724 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association of the C-Reactive Protein Gene (CRP) rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis.

Wypasek Ewa E Potaczek Daniel P DP Undas Anetta A

International journal of molecular sciences 20151009 10

Elevation in C-reactive protein (CRP) levels have been shown in patients with aortic valve stenosis (AS). Minor allele of the CRP gene (CRP) rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for ...[more]

PMID: 26473826

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Project description:ImportanceDiagnosis of low-gradient severe aortic stenosis (AS) is challenging. We hypothesized that the time between left ventricular (LV) and aortic systolic pressure peaks (TLV-Ao) is associated with aortic stenosis (AS) severity and may have additive value in diagnosing severe AS, especially in patients with low-gradient AS.ObjectiveTo investigate the diagnostic utility of measuring catheter-based TLV-Ao in patients with severe AS.Design, setting, and participantsWe studied 123 patients with severe AS at the Cleveland Clinic Foundation, a tertiary referral center, who underwent transcatheter aortic valve replacement (TAVR) via femoral access and had pre-TAVR cardiac computed tomography assessment and hemodynamic measurements recorded during a TAVR procedure. All patients received hemodynamic evaluation, echocardiographic assessment, and quantification of aortic valve calcification (AVC) by multidetector computed tomography. Hemodynamic data were collected via left heart catheterization done just before TAVR, and TLV-Ao was calculated offline. Data were analyzed between October 5, 2015, and July 20, 2016.Main outcomes and measuresThe association between TLV-Ao and AVC or other conventional imaging parameters was analyzed.ResultsOf the included patients, the mean (SD) age was 81 (9) years, and 65 (54%) were men (54%). Among 123 patients, 48 patients (39%) had low-gradient AS (<40 mm Hg) and mean (SD) TLV-Ao was 69 (39) milliseconds. In multivariable logistic regression analyses, higher TLV-Ao (odds ratio [OR], 1.02; 95% CI, 1.01-1.04; P = .002) and higher peak aortic valve (AV) velocity (OR, 1.01; 95% CI, 1.00-1.02; P = .008) were independently associated with severe AVC (AVC >1000 AU). Adding TLV-Ao to the peak AV velocity and AV area showed significant incremental value to be associated with AVC, with a net reclassification improvement of 0.61 (95% CI, 0.23-0.99; P = .002) and integrated discriminatory improvement of 0.09 (95% CI, 0.03-0.16; P = .003). In a subgroup of patients with low-grade AS, higher TLV-Ao was the only parameter associated with severe AVC (OR, 1.02; 95% CI, 1.001-1.04; P = .03).Conclusions and relevanceProlonged TLV-Ao was associated with severe AVC. This catheter-based hemodynamic index may be an additional surrogate to differentiate low-gradient true severe AS. Larger, prospective studies investigating the role of TLV-Ao as a marker of clinical outcomes in patients undergoing TAVR are required.

Dataset Information

Association of the C-Reactive Protein Gene (CRP) rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis.

Publications

Association of the C-Reactive Protein Gene (CRP) rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis.

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