Schneider Simon, Hoppmann Petra, Koch Werner, Kemmner Stephan, Schmaderer Christoph, Renders Lutz, Kastrati Adnan, Laugwitz Karl-Ludwig, Heemann Uwe, Baumann Marcus
I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Deutsches Herzzentrum München, Technical University Munich, Munich, Germany.
J Inflamm (Lond). 2015 Oct 1;12:57. doi: 10.1186/s12950-015-0100-5. eCollection 2015.
Obesity is strongly associated with hypertension. Despite numerous mechanistic links the association is not fully understood. Western diet increases uptake of Toll-Like receptor 4 (TLR4) ligands such as free fatty acids or endotoxin. We recently demonstrated that TLR4 ligands are involved in the development of hypertension. We hypothesized that TLR4 ligands are involved in obesity-associated hypertension and investigated the TLR4 single nucleotide polymorphism (SNP rs 498790). This SNP is frequent, associated with cardiovascular disease and characterized by blunted response upon exposure to TLR4 ligands.
We investigated 3657 patients undergoing coronary angiography. Blood pressure was determined in standardized manner prior angiography. The diagnosis of hypertension was based on record data. Patients were characterized for TLR4 single nucleotide polymorphism (SNP) rs4986790. Patients were stratified according to quartiles of Body mass index (BMI) and according to the polymorphism. The association between the TLR4 polymorphism and blood pressure in obese patients (BMI > 30 kg/m(2)) was investigated by multivariate regression analysis.
Out of 3657 patients 3017 patients fulfilled inclusion criteria. In the whole cohort a significant increase of SBP, pulse pressure and diagnosis of hypertension was observed across BMI quartiles. By contrast, no significant increase of SBP, pulse pressure or diagnosis of hypertension was observed in the 319 cases with TLR4 SNP rs4986790 across BMI quartiles. These obese cases had significantly lower SBP, lower pulse pressure (7.0 and 7.6 mmHg) and less diagnosis of hypertension as controls. In obesity the TLR4 SNP rs4986790 was an independent predictor of SBP.
Systolic blood pressure increase with obesity was blunted in cases with TLR4 SNP rs4986790.
肥胖与高血压密切相关。尽管存在众多机制联系，但这种关联尚未完全明确。西方饮食会增加对Toll样受体4（TLR4）配体（如游离脂肪酸或内毒素）的摄取。我们最近证明TLR4配体参与高血压的发生发展。我们推测TLR4配体参与肥胖相关高血压，并研究了TLR4单核苷酸多态性（SNP rs 498790）。这种SNP很常见，与心血管疾病相关，其特征是暴露于TLR4配体时反应迟钝。
我们研究了3657例接受冠状动脉造影的患者。在血管造影前以标准化方式测定血压。高血压的诊断基于记录数据。对患者进行TLR4单核苷酸多态性（SNP）rs4986790检测。根据体重指数（BMI）四分位数和多态性对患者进行分层。通过多变量回归分析研究肥胖患者（BMI>30 kg/m²）中TLR4多态性与血压之间的关联。
3657例患者中有3017例符合纳入标准。在整个队列中，观察到BMI四分位数间收缩压、脉压和高血压诊断率显著增加。相比之下，在319例具有TLR4 SNP rs4986790的患者中，BMI四分位数间未观察到收缩压、脉压或高血压诊断率的显著增加。与对照组相比，这些肥胖病例的收缩压显著更低，脉压更低（分别低7.0和7.6 mmHg），高血压诊断率更低。在肥胖患者中，TLR4 SNP rs4986790是收缩压的独立预测因子。
在具有TLR4 SNP rs4986790的病例中，肥胖导致的收缩压升高不明显。
