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Introduction: According to the world health organization, an estimated 1.13 billion individuals worldwide have hypertension (HT). However, limited studies discussed the risk prediction for incident HT. We aim to evaluate the incidence of HT and identify its risk factors in urban Japanese residents. Methods: We followed up 4,314 normotensive participants at the baseline survey. Blood pressure (BP) was measured twice in the sitting position under rest. The participants have continued to visit the center every two years for regular health check-ups and all of them gave informed consent. The BP categories were defined by the ESC/ESH Guidelines. Cox regression model was used to detect HT's risks by cardiovascular risk factors. Results: During the mean follow-up period of 17.6 years, 25.8 per 1000 person-years of participants developed HT (optimal 16.7, normal 30.7, and elevated BPs 43.5 per 1000 person-years, respectively). The adjusted hazards ratio (HRs, 95% CIs) for developing HT for age groups in the 40s (HR=1.34, 95% CI=1.14 - 1.58), 50s (1.73, 1.47 - 2.04), 60s (2.26, 1.91 - 2.68), and 70s (2.95, 2.41 - 3.61), normal BP (2.23, 1.98 - 2.50), elevated BP (4.25, 3.78 - 4.76), smoking > 10 cig/d (1.21, 1.05 - 1.40), never drinking alcohol 1.22 (1.07 - 1.40), drinking alcohol ≥ 4 units/day 1.36 (1.15 - 1.60), parental history of HT (1.18, 1.03 - 1.34), fasting plasma glucose levels ≥ 126 mg/dL (1.39, 1.10 - 1.76), and chronic kidney disease (1.15, 1.02 -1.29) in the normotensive population. Conclusion: The incident and risk factors for developing HT were firstly shown in Japan. The study emphasizes the importance of controlling the risk factors for incident HT as primary prevention.

Purpose: We have first reported that the new progression of carotid artery plaque (Prog-PQ) is a risk factor for incident cardiovascular disease (CVD), but the Prog-PQ risk score has not been established. Methods: We studied 4,724 Japanese (mean age 59.7 years) without CVD, whose intima-media thickness (IMT) was measured with carotid ultrasonography on both sides of the entire carotid artery areas as a baseline survey (April 1994 to August 2001). We defined carotid plaque as a maximum IMT of the common carotid artery >1.1mm. We excluded subjects with carotid plaque at baseline (n=1,044), lost to follow-up (n=167), and missing data (n=2). For 3,511 subjects, carotid ultrasonographic follow-ups were performed every two years until March 2016. Blood pressures (BPs) were used the average of two measurements recorded more than 1 min apart. Cox proportional hazard ratios were analyzed after adjusting for cardiovascular risk factors. We used the area under the receiver operating characteristic curve to evaluate the model's discrimination. Results: During 38,454 person-years of follow-up, 1,771 instances of the Prog-PQ occurred. Compared to subjects with systolic BP (SBP) Conclusion: High SBP was a significant risk factor for the Prog-PQ. We have developed a 10-year risk score for the Prog-PQ, which can efficiently predict atherosclerosis in routine clinic/health examinations without carotid ultrasonography.

We previously reported the secretion of C-type natriuretic peptide (CNP) from vascular endothelial cells and proposed the existence of a vascular natriuretic peptide system composed of endothelial CNP and smooth muscle guanylyl cyclase-B (GC-B), the CNP receptor, and involved in the regulation of vascular tone, remodeling, and regeneration. In this study, we assessed the functional significance of this system in the regulation of blood pressure in vivo using vascular endothelial cell–specific CNP knockout and vascular smooth muscle cell–specific GC-B knockout mice. These mice showed neither the skeletal abnormality nor the early mortality observed in systemic CNP or GC-B knockout mice. Endothelial cell–specific CNP knockout mice exhibited significantly increased blood pressures and an enhanced acute hypertensive response to nitric oxide synthetase inhibition. Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in rings of mesenteric artery isolated from endothelial cell–specific CNP knockout mice. In addition, endothelin-1 gene expression was enhanced in pulmonary vascular endothelial cells from endothelial cell–specific CNP knockout mice, which also showed significantly higher plasma endothelin-1 concentrations and a greater reduction in blood pressure in response to an endothelin receptor antagonist than their control littermates. By contrast, vascular smooth muscle cell–specific GC-B knockout mice exhibited blood pressures similar to control mice, and acetylcholine-induced vasorelaxation was preserved in their isolated mesenteric arteries. Nonetheless, CNP-induced acute vasorelaxation was nearly completely abolished in mesenteric arteries from vascular smooth muscle cell–specific GC-B knockout mice. These results demonstrate that endothelium-derived CNP contributes to the chronic regulation of vascular tone and systemic blood pressure by maintaining endothelial function independently of vascular smooth muscle GC-B.

Background and Purpose: We observed that the maximum of intima-media thickness (IMT) more than 1.1 mm in the common carotid artery (CCA), i.e. CIMT-plaque, is the best predictive marker for incident cardiovascular disease (CVD) in the Suita Study. There has been no study of the association between the progress of carotid atherosclerosis and CVD in a general population. We assessed our hypothesis that CIMT-plaque progression could predict the risk of new-onset CVD in a general population. Methods: We studied 3,722 men and women (mean age 59.8 years without CIMT-plaque or CVD at baseline) who completed a baseline survey and carotid ultrasonography. CIMT-plaque was defined as a maximum IMT in the CCA more than 1.1 mm. During the follow-up periods from April 1994 to March 2005, we observed 632 new CIMT-plaques. After new incident CIMT-plaque or as of April 2005, we conducted a prospective cohort study of the cases until the December 2013 endpoint. We compared the CVD risk by a Cox proportional hazards model after adjusting for age, sex, body mass index, prehypertension, hypertension (grades I and II+III), TC, HDL, antihypertensive drug and/or statin use, diabetes, impaired fasting glucose, chronic kidney disease, smoking, and excessive drinking (more than 4 units/day). Results: After new incident CIMT-plaques in CCA, we observed 234 incident CVD events (139 strokes and 95 coronary heart disease [CHD]) during 38,243 person-years of follow-up. Age, men, hypertension grades I and II+III, diabetes, and hypercholesterolemia were associated with the progression of CIMT-plaque. After new incident CIMT-plaques, the adjusted hazard ratios (95% confidence intervals) for CVD, stroke, and IHD during follow-up were 1.58 (1.15 to 2.17), 1.54 (1.03 to 2.31), and 1.72 (1.03 to 2.88). Conclusions: The novel finding of this study is that CIMT-plaque progression could be a good predictor of new-onset CVD in a general population.