Therapeutic modification of arterial stiffness:An update and comprehensive review

Arterial stiffness has been recognized as a marker of cardiovascular disease and associated with longterm worse clinical outcomes in several populations. Age, hypertension, smoking, and dyslipidemia, known as traditional vascular risk factors, as well as diabetes, obesity, and systemic inflammation lead to both atherosclerosis and arterial stiffness. Targeting multiple modifiable risk factors has become the main therapeutic strategy to improve arterial stiffness in patients at high cardiovascular risk. Additionally to life style modifications, long-term ω-3 fatty acids(fish oil) supplementation in diet may improve arterial stiffness in the population with hypertension or metabolic syndrome. Pharmacological treatment such as reninangiotensin-aldosterone system antagonists, metformin, and 3-hydroxy-3-methyl-glutaryl-Co A reductase inhibitors were useful in individuals with hypertension and diabetes. In obese population with obstructive sleep apnea, weight reduction, aerobic exercise, and continuous positive airway pressure treatment may also improve arterial stiffness. In the populations with chronic inflammatory disease such as rheumatoid arthritis, a use of antibodies against tumor necrosis factor-alpha could work effectively. Other therapeutic options such as renal sympathetic nerve denervation for patients with resistant hypertension are investigated in many ongoing clinical trials. Therefore our comprehensive review provides knowledge in detail regarding many aspects of pathogenesis, measurement, and management of arterial stiffness in several populations, which would be helpful for physicians to make clinical decision.

Perspective of future drugs targeting sterile 20/SPS1-related proline/alanine-rich kinase for blood pressure control

According to a genome-wide association study,intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase(SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes,mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge,phosphorylation of upstream with-no-lysine(K)(WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3-Cullin 3 E3 ligase,hyperinsulinemia,and low potassium intake to mediate hypertension have been identified. In addition,the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010,two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently,two novel SPAK inhibitors for mice,Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK(gene or kinase).

Metabolic biomarkers and long-term blood pressure variability in military young male adults

BACKGROUND Metabolic syndrome is a cluster of cardiovascular risk factors, including central obesity, high blood pressure, elevated plasma glucose, reduced high-density lipoprotein and elevated triglyceride levels.AIM To investigate the relationship between metabolic biomarkers and long-term blood pressure variability(BPV) in young males.METHODS A cohort of 1112 healthy military males aged 18-40 years from the cardiorespiratory fitness and hospitalization events in armed forces study in eastern Taiwan was prospectively included. The following metabolic biomarkers were used: Waist circumference, serum uric acid(SUA), triglycerides, high density lipoprotein, triglycerides, and fasting glycose. BPV was assessed by average real variability(ARV) and standard deviation(SD) across 4 clinic visits during the study period(2012-14, 2014-15, 2015-16, and 2016-18). Multivariable linear regression analysis was used to determine the association after adjusting for age, body mass index, systolic and diastolic blood pressure(SBP and DBP),lipid profiles, physical activity, alcohol intake and tobacco smoking status.RESULTS In the unadjusted model, waist circumference was significantly and positively correlated with ARVDBP and SDDBP [β(standard errors) = 0.16(0.049) and 0.22(0.065), respectively], as was SUA [β = 0.022(0.009) and 0.038(0.012),respectively]. High-density lipoprotein was negatively correlated with ARVSBP [β=-0.13(0.063)]. There were no associations with the other metabolic biomarkers.In contrast, only SUA was significantly correlated with SDSBP and SDDBP [β = 0.019(0.011) and 0.027(0.010), respectively] in the adjusted model.CONCLUSION Our findings showed that of traditional metabolic biomarkers, SUA had the strongest positive correlation with long-term systolic and diastolic BPV in young male adults, and the clinical relevance needs further investigation.