Involvement of Arterial Stiffness and Inflammation in Hyperuricemia-Related Development of Hypertension

Abstract

A ccording to recently reported meta-analyses, hyperuricemia is an independent risk factor for the development of hypertension, 1,2 although the underlying mechanisms have not yet been fully clarified. Hyperuricemia has also been reported to be associated with the early stages of development of some risk factors for hypertension, such as arterial stiffness, 3 renal function decline, 4 and inflammation. 5 Thus, we attempted to verify the possibility of involvement of these risk factors in the risk of development of hypertension associated with hyperuricemia. 6 Although an observational study would be needed for such an objective, conventional observational studies, in which the relevant assessments are conducted at 2 observational points, have the limitation that they exclude the effects of timevarying confounding variables.7 However, analysis of repeated measures data by mixed model linear (MML) regression analysis and general estimated equation (GEE) analysis may be useful to minimize the effects of time-varying confounders. In the present prospective observational study conducted in Japanese men without hypertension at the study baseline, we analyzed repeated measures data by MML regression analysis and GEE analysis to clarify the longitudinal associations of hyperuricemia with the above-mentioned risk factors for the development of hypertension, and then to examine the longitudinal associations of these risk factors with the development of hypertension. MethodsThe data, analytical methods, and study materials will not be made available to other researchers for the purpose of reproducing the results or replicating the procedure. Design and SubjectsThe present study was conducted in the same cohort as that used in a previously reported prospective observational study. 8,9 The cohort consisted of employees working at the headquarters of a single large Japanese construction company located in downtown Tokyo. According to the Occupational Health and Safety Law in Japan, it is mandatory for all company employees to undergo annual health checkups. Informed consent for participation in this study was obtained from all of the study participants before their enrollment in this study. The study was Correspondence to Hirofumi Tomiyama, Department of Cardiology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Tokyo 160-0023, Japan. Email tomiyama@tokyo-med.ac.jp See Editorial Commentary, pp 582-584Abstract-This study analyzed repeated measurement data to clarify the longitudinal associations between hyperuricemia and the risk factors for the development of hypertension (ie, increased arterial stiffness, renal dysfunction, and inflammation), and then examined whether these risk factors show longitudinal associations with the development of hypertension. In 3274 Japanese men without hypertension, the brachial-ankle pulse wave velocity, blood pressure, estimated glomerular filtration rate, and serum uric acid and CRP (C-reactive protein) levels were measured annually over an 8-year period. Of these, 474 subjects developed hy...

Impact of monocyte to high-density lipoprotein ratio on prevalent hyperuricemia: findings from a rural Chinese population

“…Chronic inflammation is a pathophysiological process characterized by elevated inflammatory mediators which closely associate with hyperuricemia [7,8]. Epidemiological reports have demonstrated a significant correlation between inflammation and elevated uric acid level [2,9]. Consistently, previous studies have shown that hyperuricemia might induce inflammation by activating the expression of inflammatory mediators [10,11].…”

“…Recent clinical and epidemiological studies have established that MHR has the ability to predict multiple inflammation-related diseases, such as metabolic syndrome, diabetes mellitus, atrial fibrillation and coronary artery disease [21][22][23][24]. Recent researches have revealed the significant association between inflammation and elevated uric acid level [2,9]. For example, Creactive protein (CRP), a marker of low-grade inflammation, was positively correlated with SUA levels [36,37].…”

“…In recent decades, hyperuricemia is becoming a major public health issue due to its close association with critical diseases such as gout, hypertension, diabetes mellitus, chronic kidney disease and other cardiovascular diseases (CVD) [1][2][3][4][5][6]. For example, the Mendelian randomization study supported that hyperuricemia may play a causal role in the development of CVD, suggesting its great significance for early screening and prevention of CVD [5].…”

<p>Uric Acid and Arterial Stiffness</p>

“…99 Hyperuricemia was also a predictor for the development of hypertension in patients with prehypertension, after adjusting for classical risk factors. 100 Tomiyama et al 101 also found a longitudinal association between hyperuricemia and hypertension in 3274 Japanese men without hypertension followed up over a period of 8 years. UA, baPWV, C-reactive protein, estimated glomerular filtration rate and blood pressure were measured annually.…”

Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Radix Puerariae for Treatment of Hypertension

“…Chronic low-grade inflammation is one of the many putative mechanisms for hypertension, with elevated levels of inflammatory cytokines and activation of the immune system (Ruan and Gao, 2019). Some studies have suggested that the risk of hypertension is positively correlated with increased inflammation (Tomiyama et al, 2018;Jayedi et al, 2019). Moderate increases in blood pressure activate T cells, which in turn promote inflammation, which further increases blood pressure, leading to severe hypertension (Harrison et al, 2012).…”