Aims: This prospective observational study, which utilized repeated annual measurements performed over a 9-year period, applied mixed model analyses to examine age-related differences in longitudinal associations between alcohol intake and arterial stiffness, pressure wave reflection, and inflammation. Methods: In 4016 middle-aged (43±9 years) healthy Japanese male employees, alcohol intake, brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and serum C-reactive protein (CRP) levels were measured annually during a 9-year study period. Results: The estimated marginal mean baPWV (non-drinkers=1306 cm/s, mild–moderate drinkers=1311 cm/s, and heavy drinkers=1337 cm/s, P ＜0.01) and that of rAI showed significant stepped increases in an alcohol dose-dependent manner in the entire cohort, but an increase in rAI was not observed in subjects aged ≥ 50 years. The estimated slope of the annual increase in baPWV, but not rAI, was higher for heavy drinkers than for non-drinkers (slope difference, 1.84; P ＜0.05), especially for subjects aged ＜50 years (slope difference, 2.84; P ＜0.05). Conclusion: In middle-aged male Japanese employees, alcohol intake may attenuate inflammatory activity. While alcohol intake may exacerbate the progression of arterial stiffening in a dose-dependent manner without mediating inflammation, especially in subjects under 50 years of age, it may promote pressure wave reflection abnormalities with aging at earlier ages without further exacerbation at older ages.

Objective: Obstructive sleep apnea (OSA) is recognized as an independent risk factor for cardiovascular disease. On the other hand, inter-arm systolic blood pressure difference (IAD), inter-ankle systolic blood pressure difference (IAND), and ankle-brachial index (ABI) are all known predictors of cardiovascular events. The aim of the present study was to investigate the association between OSA and four-limb blood pressure differences.Methods: We conducted this cross-sectional study in a large sleep cohort from Tokyo Sleep Heart Study. In 2643 consecutive patients who visited our sleep clinic for polysomnography between 2005 and 2017, all the patients underwent blood pressure measurement simultaneously in all the four limbs by oscillometric methods. Results:The prevalence rate of IAD !10 mmHg was significantly higher in the moderate OSA (15 apneahypopnea index [AHI] < 30) group (4.2%) and severe OSA (AHI ! 30) group (4.6%) than that in the no/mild (AHI < 15) OSA group (1.4%). Multivariate logistic regression analysis also identified moderate to severe OSA as being significantly associated with IAD !10 mmHg, even after adjustments for confounding variables (moderate OSA: odds ratio [OR], 4.869; 95% confidence interval [CI], 1.080-21.956; P ¼ 0.039; severe OSA: OR, 5.301; 95% CI, 1.226-22.924; P ¼ 0.026). However, there were no significant associations of the OSA severity with IAND !15 mmHg or ABI <0.9.Conclusions: Moderate to severe OSA was independently associated with the IAD, not but with the IAND or ABI.

Objective: To investigate the association of RDW and VTE including deep vein thrombosis (DVT) and pulmonary embolism (PE) and related mortality.Methods: Major medical databases were systematically searched for observational studies which assessed the association of RDW and VTE published until May 2022. The databases were searched with predefined protocol without language restriction based on PRISMA guidelines. The analysis was performed in RevMan 5.3 to provide pooled measures for Risk Ratio (RR) and weighted mean difference (WMD).Results: Twenty-three studies were enrolled including 6,737 cases and 58,831 controls. Higher RDW was indicated as independent predictors for VTE compared to lower RDW (RR = 1.82, p < 0.00001), comprising DVT and PE (RR = 1.6, p < 0.00001, and RR = 2.05, p = 0.002, respectively). There was also an association between higher RDW and risk of mortality after PE episode with RR = 1.4 (p = 0.0004), involving short-(30-day) and long-term (> 1 year) mortality (RR = 1.79, p = 0.04, and RR = 1.15,p = 0.03, respectively). Compared to lower RDW, higher RDW also revealed a significant association with unprovoked VTE (RR = 2.18, p = 0.02). VTE-group had a higher mean of RDW compared to control with WMD = 1.13% (p < 0.00001), consisting of PE-group (WMD = 0.99%, p < 0.00001) and DVT-group (WMD = 1.07%, p < 0.00001). Among PE patients, The PE-related mortality group also had a higher mean of RDW in comparison to the survivor group with WMD = 1.97%, (p < 0.00001). Conclusions:Higher RDW value was associated with the occurrence of VTE, including DVT, PE, unprovoked VTE, and PE-related mortality. Therefore, the use of the potential role of RDW should be emphasized since it is low-cost and simple to obtain, even in a low-resource setting.

Objective: Metabolic syndrome is related with insulin resistance and the close relation between hypertension and insulin resistance has been demonstrated. On ant-hypertensive drugs, organ-protective action other than antihypertensive action is important and should be considered when we select antihypertensive drugs.Long-acting calcium antagonists have action of improving insulin resistance other than antihypertensive action. In this study, we examined effect of improving insulin resistance in azelnidipne of long-acting calcium antagonist in Japanese hypertensive patients with metabolic syndrome. Design and method:This study included 25 patients (14 men and 11 women; mean age 54.6 years) of Japanese hypertensive patients with metabolic syndrome who had prior antihypertensive treatment with ARB (poor BP control with BP > 140/90 mmHg) or no treatment. These patients were given azelnidipine 16 mg/day and the following indices were measured before and 3-6 months of azelnidipine therapy to compare their variations: systolic BP, diastolic BP, heart rate, fasting plasma glucose, fasting immunoreactive insulin(F-IRI), homeostasis model assessment for insulin resistance(HOMA-R) and HbA1c. Results:The mean BP was 153/90 mmHg before azelnidipine therapy but significantly decreased to 137/80 mmHg after therapy. Heart rate also significantly decreased from 88bpm to 81bpm. F-IRI significantly decreased from 15.0 microIU/ ml to 10.1 microIU/ml. HOMA-R significantly decreased from 3.66 to 2.40. Other parameters had no significant changes. Conclusions:In Japanese hypertensive patients with metabolic syndrome who had prior antihypertensive treatment with ARB (poor BP control) or no treatment, azelnidipine therapy significantly decreased BP and heart rate and improved insulin resistance. It is speculated that this phenomenon is caused by azelnidipine effect of inhibiting the sympathetic nervous system. This study showed that azelnidipine therapy is useful for hypertensive patients with metabolic syndrome.

Background and Aim:Obesity is a causal factor for conventional risk factors for cardiovascular disease (CVD), and these risk factors affect increased arterial stiffness and also abnormal pressure wave reflection in arterial tree. Even so, because of the potent direct influences of these risk factors on arterial stiffness and pressure wave reflection, the direct effect of obesity on these vascular abnormalities has been still controversial. Then, the present study examined the effect of weight gain on those vascular abnormalities.Methods and Results:In 4016 middle-aged (43 ± 9 years) healthy Japanese men without CVD at the study baseline, body weight, risk factors for CVD, brachial-ankle pulse wave velocity (baPWV), and radial augmentation index (rAI) were measured at the baseline and end of study period (mean duration of follow-up was 6.3 years). The study subjects were divided into 3 groups by the change of BMI during the study period. While the change of baPWV in the highest tertile range of increase in BMI (57 ± 138 cm/sec) was larger than that in the lowest tertile range of increase in BMI (46 ± 136 cm/sec)(P < 0.05), these differences were not significant after the adjustment of changes of blood pressure. In addition, the change of rAI was similar between both groups.Conclusions:Weight gain may affect increase in arterial stiffness rather than abnormal pressure wave reflection, and this effect may be mediated by increase in blood pressure related to weight gain rather than the direct effect of weight gain.