Enhancing the Efficacy of Antihypertensive Treatment with Pharmacogenomics

In 2003,two newguidelines for hyperten—sive prevention andmanagement have beenprovided by AmericanJNC7 and European So-ciety of Hypertension.They advocated that thephysician should choosedrugs following individ—ualized treatment,

Endogenous hydrogen sulfide and ERK1/2-STAT3 signaling pathway may participate in the association between homocysteine and hypertension

Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.

Evaluation of the neutrophil to lymphocyte ratio in newly diagnosed nondiabetic hypertensive patients with carotid atherosclerosis

Background Carotid intimal thickness(IMT),a marker of subclinical atherosclerosis,was widely used for predicting cardiovascular events. Recent studies have shown that inflammation plays a vital role in the development and progression of atherosclerosis. The neutrophil to lymphocyte ratio(NLR)is a new marker of inflammation because it is closely related to cardiovascular,metabolic and inflammatory diseases. However,the relationship between NLR and carotid atherosclerosis is currently unknown. Methods A total of 882 patients underwent blood sampling for neutrophil and lymphocyte counts,serum lipids,total homocysteine(tHcy),and carotid scan by ultrasonography(US)to evaluate abnormalities of carotid wall. Results NLR was found to be statistically significantly higher in the carotid atherosclerosis group(2.0±0.8 vs. 1.7±0.6,P<0.001). The NLR,expressed as both quartiles(odds ratio[OR],2.36;95% confidence interval[CI],1.37 to 3.47;P=0.001)and continuous values(OR,1.83;95% CI,1.43 to 2.33;P<0.001),was significantly associated with a higher risk for carotid atherosclerosis. The optimal NLR cutoff value for detecting carotid atherosclerosis was 1.60 based on receiver operating curve(ROC)analysis with a sensitivity of 64.0% and a specificity of 57.0%. Conclusion NLR is significantly associated with carotid atherosclerosis in newly diagnosed nondiabetic hypertensive patients.

Prevalence and risk factors of hypertension in southern China guided by new ACC guideline

Background Hypertension is one of the most common chronic diseases which threatens human health. However,epidemic data of hypertension guided by new ACC hypertension guideline is limited. Methods Residents from four cities in urban and country areas were enrolled by the probability proportional to size method in Guangdong province,China. Results A total of 19,031 participants were enrolled. The age-standardized prevalence of hypertension was 32.07% guided by previous guideline and 56.67%guided by the new guideline. Notably,when guided by new guideline,the prevalence of hypertension in younger(15~24 years,313%;25~34 years,270%;35~44 years,186%),lower body mass index(BMI<24 kg/m^2,102%)and high-educated(undergraduates,194%;postgraduates,137%)participants increased more compared to older(55~64 years,47%;65~74 years,33%;75~84 years,23%),obesity(BMI≥28 kg/m^2,46.6%)and low-educated(primary school,42%)participants. Age,gender,alcohol taking,BMI,waist circumference,education,medical insurance and hypertension family history were found to be independent risk factors of hypertension in new guidelines. Conclusions The prevalence of hypertension changed greatly when guided by the new hypertension guideline. When applying the new hypertension guideline,subjects with younger age,lower BMI and high-educated tend to be more susceptible to hypertension compared to traditional high risk population. Further studies are needed to explore indicators that can predict the morbidity of hypertension.