A rterial stiffness is well-recognized as an important predictor of development of cardiovascular disease (CVD), 1,2 and meta-analyses of prospective cohort studies have revealed that increase in the carotid-femoral pulse wave velocity (cfPWV) is associated with an increase in the risk of development of CVD. 3,4 However, the cfPWV is measured by tonometry or Doppler, which requires specialized training and exposure of the inguinal region. 5,6Abstract-An individual participant data meta-analysis was conducted in the data of 14 673 Japanese participants without a history of cardiovascular disease (CVD) to examine the association of the brachial-ankle pulse wave velocity (baPWV) with the risk of development of CVD. During the average 6.4-year follow-up period, 687 participants died and 735 developed cardiovascular events. A higher baPWV was significantly associated with a higher risk of CVD, even after adjustments for conventional risk factors (P for trend <0.001). When the baPWV values were classified into quintiles, the multivariableadjusted hazard ratio for CVD increased significantly as the baPWV quintile increased. The hazard ratio in the subjects with baPWV values in quintile 5 versus that in those with the values in quintile 1 was 3.50 (2.14-5.74; P<0.001). Correspondence to Hirofumi Tomiyama, Department of Cardiology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Tokyo, Japan. E-mail tomiyama@ tokyo-med.ac.jp In the early 2000s, a simple device for measurement of the brachial-ankle pulse wave velocity (baPWV) was launched for clinical use. Brachial-Ankle Pulse Wave Velocity and the Risk Prediction of Cardiovascular Disease An Individual Participant Data Meta-Analysis7 baPWV is automatically measured using a separate cuff for each of the 4 limbs by an oscillometric method. baPWV may be more easily applied in clinical practice than the cfPWV because of the simplicity and ease of its measurement.7,8 baPWV has been reported to be closely correlated with the directly measured aortic PWV and cfPWV. 9 A recent meta-analysis using summary data from the literature has demonstrated that higher levels of baPWV were associated with an increased risk of development of CVD.10 However, most of the studies included in the meta-analyses were conducted in patients with a high CVD risk (patients with CVD or end-stage renal disease), and thus, the usefulness of baPWV to assess the risk of development of CVD in subjects with a low to intermediate CVD risk as assessed using the Framingham risk score (FRS) had not been clearly elucidated. Furthermore, these studies did not determine the predictive ability for CVD over that of the traditional risk factors. Therefore, we conducted a meta-analysis using individual participant data (IPD) from prospective cohort studies to clarify whether baPWV could be used as an independent marker to predict the risk of development of CVD in subjects without preexisting CVD. Methods Study PopulationJ-BAVEL (Japan Brachial-Ankle Pulse Wave Velocity Individual Participant Data Meta-Analysis of Pros...

Abstract-Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that cleaves angiotensin II to angiotensin 1-7.Recently, it was reported that mice lacking ACE2 (ACE2 Ϫ/y mice) exhibited reduced cardiac contractility. Because mechanical pressure overload activates the cardiac renin-angiotensin system, we used ACE2Ϫ/y mice to analyze the role of ACE2 in the response to pressure overload. Twelve-week-old ACE2 Ϫ/y mice and wild-type (WT) mice received transverse aortic constriction (TAC) or sham operation. Sham-operated ACE2 Ϫ/y mice exhibited normal cardiac function and had morphologically normal hearts. In response to TAC, ACE2 Ϫ/y mice developed cardiac hypertrophy and dilatation. Furthermore, their hearts displayed decreased cardiac contractility and increased fetal cardiac gene induction, compared with WT mice. In response to chronic pressure overload, ACE2 Ϫ/y mice developed pulmonary congestion and increased incidence of cardiac death compared with WT mice. On a biochemical level, cardiac angiotensin II concentration and activity of mitogen-activated protein (MAP) kinases were markedly increased in ACE2 Ϫ/y mice in response to TAC. Administration of candesartan, an AT 1 subtype angiotensin receptor blocker, attenuated the hypertrophic response and suppressed the activation of MAP kinases in ACE2 Ϫ/y mice. Activation of MAP kinases in response to angiotensin II was greater in cardiomyocytes isolated from ACE2 Ϫ/y mice than in those isolated from WT mice. ACE2 plays an important role in dampening the hypertrophic response to pressure overload mediated by angiotensin II. Disruption of this regulatory function may accelerate cardiac hypertrophy and shorten the transition period from compensated hypertrophy to cardiac failure.

Lead-based perovskite solar cells have gained ground in recent years, showing efficiency as high as 20%, which is on par with that of silicon solar cells. However, the toxicity of lead makes it a nonideal candidate for use in solar cells. Alternatively, tin-based perovskites have been proposed because of their nontoxic nature and abundance. Unfortunately, these solar cells suffer from low efficiency and stability. Here, we propose a new type of perovskite material based on mixed tin and germanium. The material showed a band gap around 1.4-1.5 eV as measured from photoacoustic spectroscopy, which is ideal from the perspective of solar cells. In a solar cell device with inverted planar structure, pure tin perovskite solar cell showed a moderate efficiency of 3.31%. With 5% doping of germanium into the perovskite, the efficiency improved up to 4.48% (6.90% after 72 h) when measured in air without encapsulation.

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SummaryGenome-wide DNA methylation analysis indicated that DNA methylation alterations are already present even at the precancerous NASH stage, clearly differing from such alterations in viral hepatitis or cirrhosis, and possibly continuing to participate in NASH-related multistage hepatocarcinogenesis.

Aim: Arterial stiffness has been reported to correlate with cardiovascular disease (CVD). Brachialankle pulse wave velocity (baPWV) is easy to measure and has been used as a marker to evaluate arterial stiffness. The objective of the present study was to determine the cut-off value of baPWV for predicting cardiovascular prognosis in a prospective cohort study. Methods: Four hundred forty patients with essential hypertension were analyzed in study 1 with a mean follow-up of 6.3±0.1 years. Four hundred patients from study 1 who did not have a past history of CVD and/or stroke were analyzed in study 2 with a mean follow-up of 6.4±0.1 years. Stroke, CVD, and death were the primary endpoints. Results: Receiver operating characteristic (ROC) curve analysis revealed that 1750.0 cm/sec is an appropriate cut-off value for baPWV to predict the onset of stroke, CVD, stroke＋CVD, and total mortality (area under curve: 0.576-0.719). A baPWV higher than 1750.0 may also be a significant and independent risk factor for the onset of CVD＋stroke (relative risk: 2.048 (1.176-3.616), p= 0.0113 in study 1; relative risk: 1.920 (1.028-3.634), p = 0.0408 in study 2). Conclusions: The present study indicates that 1750.0 cm/sec could be a useful cut-off value for baPWV to predict cardiovascular prognosis. J Atheroscler Thromb, 2013; 20:391-400.

The purpose of the study was to investigate the association of serum uric acid (UA) levels in hypertensive patients with the prognosis for cardiovascular disease (CVD) and mortality. This hospital-based cohort study included 669 patients with essential hypertension. A questionnaire was used to identify patients in whom hypertensive complications had occurred, as well as causes of death. The primary end point of this study was new onset of stroke or CVD (new onset of angina pectoris, myocardial infarction or heart failure). We evaluated the baseline characteristics of patients, including UA levels, and assessed whether UA levels could be used to predict stroke and CVD. We also classified subjects into four groups according to the serum UA levels. During a mean follow-up period of 7.1±0.1 years, 71 strokes, 58 cases of CVD and 64 deaths were recorded. Kaplan-Meier analysis revealed that subjects in the high UA group had a higher frequency of stroke and CVD (P ¼ 0.0120) and total mortality (P ¼ 0.0021). A Cox proportional hazard model determined that, after adjusting for traditional risk factors, serum UA levels were predictive of CVD (relative risk ¼ 1.30; P ¼ 0.0073), stroke and CVD (relative risk ¼ 1.19; P ¼ 0.0141), mortality (relative risk ¼ 1.23; P ¼ 0.0353) and stroke CVD and mortality (relative risk ¼ 1.19; P ¼ 0.0083), but not stroke (P ¼ 0.4268). The significant correlations were particularly marked in women. Serum UA levels may be an independent risk factor for stroke and CVD in patients with essential hypertension, particularly women. Keywords: cardiovascular disease; mortality; prognosis; uric acid INTRODUCTION Cardiovascular disease (CVD) is one of the most severe complications of hypertension, 1-5 and many risk factors are reported to be associated with cardiovascular events in hypertensive patients. Uric acid (UA) is one of the risk factors for CVD in hypertensive patients. 6,7 Previous meta-analyses revealed that hyperuricemia may marginally increase the risk of coronary heart disease events, independent of traditional coronary heart disease risk factors, 8 and that hyperuricemia may modestly increase the risks of both stroke incidence and mortality. 9 In addition, the results of several studies indicate that a higher incidence of CVD occurs not only in patients with 'hyperuricemia' but also in patients with normal-to-high serum UA levels. [10][11][12] In contrast, some multivariate analyses have not shown that the serum UA level is a significant risk factor for CVD, independent of traditional risk factors. [13][14][15] One of the reasons proposed for this finding is that subjects with high CVD risk often also have conditions that affect the serum UA level, such as renal dysfunction, hyperinsulinemia, oxidative stress, tissue ischemia and taking diuretics for hypertension. 16,17 Moreover, UA can act as an