Adverse experiences in childhood and adolescence, defined as subjectively perceived threats to the safety or security of the child's bodily integrity, family, or social structures, are known to be associated with cardiometabolic outcomes over the life course into adulthood. This American Heart Association scientific statement reviews the scientific literature on the influence of childhood adversity on cardiometabolic outcomes that constitute the greatest public health burden in the United States, including obesity, hypertension, type 2 diabetes mellitus, and cardiovascular disease. This statement also conceptually outlines pathways linking adversity to cardiometabolic health, identifies evidence gaps, and provides suggestions for future research to inform practice and policy. We note that, despite a lack of objective agreement on what subjectively qualifies as exposure to childhood adversity and a dearth of prospective studies, substantial evidence documents an association between childhood adversity and cardiometabolic outcomes across the life course. Future studies that focus on mechanisms, resiliency, and vulnerability factors would further strengthen the evidence and provide much-needed information on targets for effective interventions. Given that childhood adversities affect cardiometabolic health and multiple health domains across the life course, interventions that ameliorate these initial upstream exposures may be more appropriate than interventions remediating downstream cardiovascular disease risk factor effects later in life.

Background-Pulmonary veins (PVs) are important sources of paroxysmal atrial fibrillation. Long-term rapid atrial pacing (RAP) changes atrial electrophysiology and facilitates the maintenance of atrial fibrillation. It is not clear whether RAP alters the arrhythmogenic activity of PVs.

This study shows that under well-designed conditions, Tai Chi exercise training could decrease blood pressure and results in favorable lipid profile changes and improve subjects' anxiety status. Therefore, Tai Chi could be used as an alternative modality in treating patients with mild hypertension, with a promising economic effect.

Thyroid hormone changes the electrophysiological activity of the PV cardiomyocytes. Increased automaticity and enhanced triggered activity may increase the arrhythmogenic activity of PVs in hyperthyroidism.

Aims Stevioside is a natural plant glycoside isolated from the plant Stevia rebaudiana which has been commercialized as a sweetener in Japan for more than 20 years. Previous animal studies have shown that stevioside has an antihypertensive effect. This study was to designed to evaluate the effect of stevioside in human hypertension. Methods A multicentre, randomized, double-blind, placebo-controlled study was undertaken. This study group consisted of 106 Chinese hypertensive subjects with diastolic blood pressure between 95 and 110 mmHg and ages ranging from 28 to 75 years with 60 subjects (men 34, women 26; mean t s.d., 54.1t3.8 years) allocated to active treatment and 46 (men 19, women 27; mean t s.d., 53.7t4.1 years) to placebo treatment. Each subject was given capsules containing stevioside (250 mg) or placebo thrice daily and followed-up at monthly intervals for 1 year. Results After 3 months, the systolic and diastolic blood pressure of the stevioside group decreased signi®cantly (systolic: 166.0t9.4±152.6t6.8 mmHg; diastolic: 104.7t5.2±90.3t3.6 mmHg, P<0.05), and the effect persisted during the whole year. Blood biochemistry parameters including lipid and glucose showed no signi®cant changes. No signi®cant adverse effect was observed and quality of life assessment showed no deterioration. Conclusions This study shows that oral stevioside is a well tolerated and effective modality that may be considered as an alternative or supplementary therapy for patients with hypertension.

Background: Stevioside, a natural glycoside isolated from the plant Stevia rebaudiana Bertoni, has been used as a commercial sweetening agent in Japan and Brazil for >20 years. Previous animal and human studies have indicated that stevioside has an antihypertensive effect.Objectives: This study was undertaken to investigate the long-term (2-year) efficacy and tolerability of stevioside in patients with mild essential hypertension. Secondary objectives were to determine the effects of stevioside on left ventricular mass index (LVMI) and quality of life (QOL).Methods: This was a multicenter, randomized, double-blind, placebocontrolled trial in Chinese men and women aged between 20 and 75 years with mild essential hypertension (systolic blood pressure [SBP] 140-159 mm Hg and diastolic blood pressure [DBP] 90-99 mm Hg). Patients took capsules containing 500 mg stevioside powder or placebo 3 times daily for 2 years. Blood pressure was measured at monthly clinic visits; patients were also encouraged to monitor blood pressure at home using an automated device. LVMI was determined by 2-dimensional echocardiography at baseline and after 1 and 2 years of treatment. QOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey. Electrocardiographic, laboratory, and QOL parameters were assessed at the beginning of treatment, and at 6 months, 1 year, and 2 years.Results: One hundred seventy-four patients (87 men, 87 women) were enrolled in the study, and 168 completed it: 82 (42 men, 40 women; mean [SD] age, 52 [7]

. Tsai JC, Chan P, Wang CH, Jeng C, Hsieh MH, Kao PF, Chen YJ, Liu JC (Taipei Medical University‐Wan Fang Hospital, Taipei, Taiwan). The effects of exercise training on walking function and perception of health status in elderly patients with peripheral arterial occlusive disease. J Intern Med 2002; 252: 448–455. Objective. To determine the effects of 12‐week exercise programme on ambulatory function, free‐living daily physical activity and health‐related quality of life in disabled older patients with intermittent claudication. Design. Prospective, randomized controlled trial. Setting. University Medical Center and Veterans Affairs Medical Center, Taipei, Taiwan. Subjects. Thirty‐two of 64 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise training and 32 to usual care control. Five patients from the exercise group and six patients from the control group dropped out, leaving 27 and 26 patients, respectively, completing the study in each group. Interventions. Twelve weeks of treadmill exercise training. Main outcome measures. Treadmill walking time to onset of claudication pain and to maximal claudication pain, 6‐min walk distance, self‐reported ambulatory ability and perceived health‐related quality of life (QOL). Results. Compliance of exercise programme was 83% of the possible sessions. Exercise training increased treadmill walking time to onset of claudication pain by 88% (P < 0.001), time to maximal pain by 70% (P < 0.001), and 6‐min walk distance by 21% (P < 0.001). Subjects. Perception of health‐related QOL improved from 12% to 178% in the exercise group. These improvements were significantly better than the changes in the control group (P < 0.05). Conclusions. Significant improvements in claudication following 12‐week exercise training in elderly PAOD patients were observed. Increase in treadmill walking time to maximal claudication pain in these patients translated into the improvement of perceived physical health, which enabled the patients to become more functionally independent.

Endothelin-1 (ET-1) has been implicated in fibroblast proliferation. However, the mechanism involving ET-1 is not clear. The present study was performed to examine the role of endogenous ET-1 in ET-1-stimulated fibroblast proliferation and to investigate the regulatory mechanism of ET-1-induced ET-1 gene expression in cardiac fibroblasts. Both ET A receptor antagonistand endothelin-converting enzyme inhibitor (phosphoramidon) inhibited the increased DNA synthesis caused by ET-1. ET-1 gene was induced by ET-1, as revealed with Northern blotting and ET-1 promoter activity assay. ET-1 increased intracellular reactive oxygen species (ROS), which were significantly inhibited by BQ485 and antioxidants. Antioxidants suppressed ET-1 gene expression and DNA synthesis stimulated by ET-1. ET-1 activated mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase, which were significantly inhibited by antioxidants. Only ERK inhibitor U0126 could inhibit ET-1-induced transcription of the ET-1 gene. Cotransfection of dominant-negative mutant of Ras, Raf, and MEK1 decreased the ET-1-induced increase in ET-1 transcription, suggesting that the Ras-Raf-ERK pathway is required for ET-1 action. Truncation and mutational analysis of the ET-1 gene promoter showed that the activator protein-1 (AP-1) binding site was an important cis-element in ET-1-induced ET-1 gene expression. Antioxidants attenuated the ET-1-stimulated AP-1 binding activity. Our data suggest that ROS were involved in ET-1-induced fibroblast proliferation and mediated ET-1-induced activation of ERK pathways, which culminated in ET-1 gene expression.