Cardiovascular risks of children with primary snoring: A 5-year follow-up study.

BACKGROUND AND OBJECTIVE: This study aimed to investigate if childhood primary snoring (PS) was associated with adverse cardiovascular outcomes at 5-year follow-up. METHODS: This was a prospective matched cohort study. Subjects were recruited from a hospital-based cohort established from years 2006 to 2012 and they were aged 6-18 years at baseline. Each subject with PS was gender, age and BMI z-score matched with a control who had normal sleep study (obstructive apnoea-hypopnoea index [OAHI] < 1/h) and without habitual snoring (<3 nights/week) at baseline. All subjects underwent measurements of flow-mediated dilation (FMD) and carotid intima-media thickness (cIMT) and sleep study at baseline and follow-up visits. Twenty-four hour ambulatory blood pressure (ABP) was also recorded at follow-up. RESULTS: Fifty-five case-control pairs were recruited and the length of follow-up was 5.1 ± 1.3 years. At follow-up visit, subjects with PS at baseline had significantly lower FMD (-0.34% [-0.59 to -0.10]), greater cIMT (+0.01 mm [+0.001 to +0.013]), higher wake systolic blood pressure (SBP) (+2.6 mm Hg [+0.02 to +5.1]), sleep SBP (+3.0 mm Hg [+0.3 to +5.6]), sleep diastolic blood pressure (+2.2 mm Hg [+0.04 to +4.4]) and sleep mean arterial pressure (+2.2 mm Hg [+0.1 to +4.2]) compared to matched controls in the fully adjusted model for variables including change in OAHI and parental history of cardiovascular diseases. CONCLUSION: Childhood PS is associated with poorer endothelial function, greater cIMT and higher ABP at 5-year follow-up irrespective of change in obstructive sleep apnoea severity.

Short Sleep Duration Is Weakly Associated with Carotid Intima-Media Thickness in Adolescents.

OBJECTIVE: To investigate the relationship between sleep duration and carotid intima-media thickness (CIMT) in adolescents. We hypothesized that short sleep duration was associated with an increased CIMT. STUDY DESIGN: This was a cross-sectional study. Healthy participants aged 10-18 years were recruited from a school-based cohort established to examine the prevalence of obstructive sleep apnea in Hong Kong. All participants completed a prospective 7-day sleep diary, underwent anthropometric measurements, overnight polysomnography, and CIMT assessment. Overweight participants or those with an obstructive apnea hypopnea index of ≥5 were excluded from analysis. Regression analysis was used to assess the association between CIMT and sleep duration and other possible correlates. RESULTS: One hundred forty-two participants completed the assessments. Male participants tended to have shorter sleep duration than females (P = .012). There were no differences in age, body mass index, Tanner developmental stage, or parental history of hypertension between groups of different sleep durations. There was a weak but significant association between short sleep duration and CIMT (r = -0.273; P < .001). CONCLUSION: Sleep duration was found to have a weakly negative association with CIMT. Further research is needed to determine whether adult adverse cardiovascular events may originate in childhood owing to short sleep duration.

Correlation of large artery intracranial occlusive disease with carotid intima-media thickness and presence of carotid plaque.

BACKGROUND AND PURPOSE: Large artery intracranial occlusive disease (LAICOD) is a predominant cause of ischemic stroke in China. Carotid intima-media thickness (CIMT) and presence of carotid plaque are also related to subsequent ischemic stroke. However, the correlation between these and LAICOD is less clear. METHODS: This was a community-based cross-sectional study. All subjects underwent carotid duplex ultrasonography and transcranial Doppler. Mean CIMT value of bilateral common carotid arteries was used. Plaque was defined as a focal CIMT of >1.5 mm. LAICOD in transcranial Doppler was defined by peak systolic velocity and age, and presence of turbulence or musical sound was also considered. RESULTS: For the 537 subjects studied (mean age, 54.7±10.1 years; 46.9% males), mean CIMT was 0.74±0.12 mm, with the 75th percentile of 0.80 mm. CIMT ≥1.0 mm was identified in 13 subjects (2.4%). Plaques were detected in 79 subjects (14.7%). Compared with those without LAICOD, the 48 subjects (8.9%) with LAICOD had greater CIMTs (0.77±0.09 versus 0.73±0.12 mm; P=0.044), more with CIMT of higher quartiles (P=0.007), and more with carotid plaques (25.0% versus 13.7%; P=0.035). However, after adjusting for confounding factors, CIMT and presence of carotid plaque were not significantly associated with LAICOD. CONCLUSIONS: The results suggest that CIMT and presence of carotid plaque probably are not independently correlated with LAICOD in Chinese community residents, which supported the existence of pathologic and pathophysiologic differences in atherogenesis of intra- and extracranial arteries.

Impact of non-cardiovascular surgery on reactive hyperaemia and arterial endothelial function.

Vascular reactivity is a surrogate marker for atherosclerosis and is predictive of cardiovascular outcome. Non-cardiovascular surgery is associated with perioperative cardiovascular complications in high-risk patients. To evaluate the impact of non-cardiovascular surgery on reactive hyperaemia and arterial endothelial function and to investigate the relationships between endothelial dysfunction and invasive (laparotomy) or minimally invasive (laparoscopic) surgery, we prospectively evaluated 106 patients undergoing abdominal surgery under general anaesthesia (71 laparotomy, 35 laparoscopy). Measurements of blood pressure, heart rate and pain (on a visual analogue scale (VAS)) were undertaken. Brachial endothelium-dependent flow-mediated dilation (FMD), endothelium-independent dilation, nitroglycerin (NTG)-induced dilation and reactive hyperaemia were measured with high-resolution B-mode ultrasound on preoperative Day 1 (baseline), as well as 2 h and 1 and 7 days postoperatively. Blood pressure and heart rate were significantly higher 2 h postoperatively. Pain, as measured on the VAS, was higher (P < 0.01) and reactive hyperaemia and FMD were significantly lower (P < 0.001) at 2 h and 1 day postoperatively compared with values at baseline and on postoperative Day 7. By postoperative Day 7, FMD had recovered to baseline levels. Patients undergoing laparoscopic surgery had less FMD reduction on Days 1 and 7 (7.5 ± 1.5% and 7.9 ± 1.5%, respectively) compared with those undergoing laparotomy (6.4 ± 1.6% (P = 0.001) and 7.0 ± 1.6% (P = 0.006), respectively), consistent with potential cardiovascular benefit. Responses to NTG were stable throughout. Backward multivariate linear regression analysis indicated that FMD was independently related to age and VAS (model R = 0.486; F = 6.4; P < 0.001). Reactive hyperaemia and arterial endothelial function are significantly reduced in the early postoperative period, particularly after laparotomy compared with laparoscopy, which may be related to postoperative cardiovascular events.

Orlistat improves endothelial function in obese adolescents: a randomised trial.

AIM: To investigate the effect of orlistat on endothelial function in obese adolescents. METHODS: Single-blind 10-week controlled trial of 67 normolipidaemic obese adolescents randomised into three groups. Group 1 (diet alone), Group 2 (diet and orlistat), Group 3 (diet, orlistat and exercise). Endothelial function measured by flow-mediated dilatation (FMD) of the brachial artery, anthropometric parameters, blood pressure, fasting blood lipids, insulin and glucose levels were recorded at baseline and at 10 weeks. RESULTS: Sixty four subjects completed the study. Groups were comparable at baseline. FMD increased significantly with orlistat (Groups 2 and 3) but not in Group 1. Orlistat treatment resulted in significantly reduced bodyweight, body mass index (BMI), waist circumference, total and low-density lipoprotein (LDL) cholesterol levels. High-density lipoprotein cholesterol levels were unchanged. Triglyceride and insulin levels were significantly reduced in all three groups. The reduction in cholesterols did not correlate with reductions in weight and BMI. A slight reduction of body fat, both with and without orlistat treatment, correlated with reduction in BMI after adjustment for baseline values. Blood pressure was unaltered by orlistat. Calorie intake was reduced with orlistat, and the decrease noted in % fat and increase in % carbohydrate was significant only in those taking orlistat. The addition of exercise (Group 3 compared with Group 2) altered no parameter. CONCLUSIONS: Orlistat improves endothelial function and reduces bodyweight, BMI, fasting total and LDL-cholesterol in obese adolescents when combined with dietary control. Improvement in endothelial function if maintained could reflect long-term cardiovascular benefit.

Inferior endothelial function improved following optimisation of asthma control in children.

Association between asthma control and cardiovascular disease (CVD) remains highly plausible as the two are related to chronic systemic inflammation. Children with physician-diagnosed asthma and matched healthy controls underwent endothelial function assessment. Repeat measurements were performed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS), compared to those with well-controlled asthma without ICS therapy. We found that children with uncontrolled asthma had inferior endothelial function compared to matched healthy controls. Enhancement in endothelial function, lung function and symptom control was observed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS). These results provided further evidence of a likely relationship between asthma control and cardiovascular health.

Salviae miltiorrhizae radix and puerariae lobatae radix herbal formula improves circulation, vascularization and gait function in a peripheral arterial disease rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: DG is a herbal formula, containing the root of Salvia miltiorrhiza Bunge (Danshen) and the root of Pueraria lobate (Willd.) Ohwi (Gegen), has a history of usage in China for cardiovascular protection and anti-atherosclerosis. AIM OF THE STUDY: The present study aims to determine the beneficial effect of DG on the hind-limb ischemia rat model which mimics peripheral arterial disease (PAD) and its vasodilative effect on isolated femoral artery. MATERIALS AND METHODS: The vasodilatory effects were assessed by contractile responses to DG in the isolated femoral artery and its underlying mechanisms were evaluated by the involvement of endothelium, potassium channel and calcium channel. For hind-limb ischemia study, treatment outcomes were assessed by evaluating hind-limb blood flow, functional limb recovery, muscle histology and angiogenesis. RESULTS: Our results demonstrated positive dose-dependent vasodilatory response to DG via an endothelium-independent mechanism that involved inwardly rectifying K+ channels and Ca2+ channels. We also demonstrated significant improvement in blood perfusion and micro-vessel density in the ischemic limb and positive effects in functional limb recovery. CONCLUSION: In conclusion, our study supported the potential use of DG as a novel treatment for symptomatic PAD.

The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model.

OBJECTIVE: To investigate the effect of water extract of Gastrodiae Rhizoma (GR) on the development of acquired temporal lobe epilepsy (TLE) and on regulating the expression of the mammalian target of rapamycin (mTOR) and semaphorin 3F (SEMA3F). METHODS: A pilocarpine-induced status epilepticus (SE) model was adopted to precipitate injury in the limbic systems. GR and carbamazepine (CBZ) treatments were given to mice for 14 days prior to SE induction to demonstrate the antiepileptic effects and continued for 5 more days to illustrate the effects on histologic studies. RESULTS: Our results consolidated that GR treatment (92.1 minutes) could delay the SE onset in comparison with the control group (61.5 minutes, P = .041). Fewer mice had reached SE with GR treatment (41.7%) when compared with the control group (83.3%, P = .044). GR treatment (2.1 hours/mouse) could suppress the number of acute seizures in post-SE survival mice when compared with the control group (4.5 hours/mouse, P < .001). The effects of GR treatment were elucidated with the mechanism of actions. GR treatment reduced the overexpression of mTOR (0.27 vs 0.67 AU/mg protein, P = .047). GR treatment increased the underexpression of SEMA3F (0.51 vs 0.16 µg/mg protein, P = .034). In the histochemical study of microtubule-associated protein 2 (MAP2) staining, our results showed that GR prevented neuronal loss in the GR treatment group (64.8% positively stained pixel area) as compared with the control group (59%, P = .014) in the hippocampus. In glial fibrillary acidic protein (GFAP) staining, the severity of astrogliosis was mitigated by the GR treatment (4.1% positively stained pixel area) when compared to the control group (5.6%, P = .047) in the hippocampus. SIGNIFICANCE: These results provide preclinical evidence to support the use of GR, which could suppress acute seizures and relieve pathological changes in pilocarpine-induced TLE mice. We demonstrated that the antiepileptic effects of GR could be accompanied by mTOR reduction and astrogliosis attenuation.

Herb-drug interaction of gastrodiae rhizoma on carbamazepine: A pharmacokinetic study in rats.

OBJECTIVE: Gastrodiae Rhizoma (GR), is a traditional Chinese Medicine that has been used for neurological disorders, including epilepsy. Epilepsy patients may be treated with adjunctive therapy of GR with antiepileptic drugs (AEDs). In particular, carbamazepine (CBZ) is of high potential to interact with concurrent treatment of Chinese Medicine. This study was to investigate the herb-drug interactions of GR and CBZ, an AED, through pharmacokinetic approach in rats. METHODS: We adopted a high-performance liquid chromatography (HPLC) system to quantify the plasma level of CBZ and its metabolite (carbamazepine-10, 11-epoxide, CBZE). The method was validated as per instructions under United States Food and Drug Administration (USFDA) guidance. For the herb-drug interaction study, rats were randomly divided into four different treatment groups: single-dose CBZ treatment, single-dose CBZ/GR treatment, 2-week course of CBZ treatment and 2-week course of CBZ/GR treatment. RESULTS: Our results demonstrated the auto-induction of CBZ metabolization when comparing single-dose with 2-week course of CBZ treatment. Pharmacokinetic interactions were noted in concomitant use of GR with CBZ by comparing two single-dose treatments (CBZ versus CBZ/GR). Our data showed that GR increased the mean residence time (MRT0-t) and the time taken to reach the maximum concentration (Tmax) of CBZ in single-dose of CBZ/GR treatment. The maximum drug concentration (Cmax) of CBZ was reduced in single-dose CBZ/GR treatment. When comparing the 2-week course of CBZ treatment with the 2-week course of CBZ/GR treatment, the MRT0-t and half-life of CBZ were increased. The AUC0-t, the Cmax and the half-life of CBZE were increased. CONCLUSION: CBZ/GR treatment may reduce the auto-induction of CBZ over 2 weeks. While the reduction of auto-induction could enhance the therapeutic effects of CBZ, it could also lead to an increase in neurological side effects and non-neurological adverse effects. Our results provided preclinical evidence of herb-drug interaction, which may have implications for epilepsy patients treated with GR.

The Impact of Lifestyle Changes on Cardiometabolic Health in Modernizing China: A Tale of Three Gorges in the Yangtze River.

Background: Modernization of Chinese adults is associated with increased atherosclerotic diseases. Over 1 million farmers have been resettled upland since 1996 in the Three Gorges dam project of the Yangtze River, with job and other lifestyle changes. We aimed to evaluate the impact of such rapid lifestyle changes on indices of cardiometabolic health. Methods: Ninety-five ex-farmers in Wu Shan (WS) (aged 49.7 ± 9 years) resettled uphill for 3-5 years and 87 age and gender-matched farmers in Da Chang (DC) (aged 48.8 ± 10 years) studied before resettlement were compared. Carotid intima-media thickness (IMT) was measured by ultrasound. Results: Ninety-nine percent WS residents adopted nonfarming jobs or were retired. WS ex-farmers had higher waist-hip ratio (P < 0.0001), low density lipoprotein-cholesterol (P = 0.001), triglycerides (P = 0.001), and prevalence of metabolic syndrome (MS) (43.2% vs. 17.2%, P = 0.01) compared with DC farmers. Smoking status, body mass index, systolic and diastolic blood pressures, high density lipoprotein-cholesterol, and fasting glucose were similar. Carotid IMT was significantly higher in WS residents (0.71 ± 0.16 mm) than in DC farmers (0.64 ± 0.11 mm) (P < 0.001). MS correlated with job changes to more sedentary nature (ß = 0.453, P < 0.0001), but not to leisure exercise activities, nor any specific dietary habits. On multivariate regression, carotid IMT was associated with WS location (ß = 0.196, P = 0.021) and presence of MS (ß = 0.208, P = 0.021), independent of other traditional vascular risk factors (model R2 value = 0.444, F-value 12.0, P < 0.0001). Conclusion: Rapid lifestyle and job changes in ex-farmers in the Three Gorges region are associated with significantly worse cardiometabolic profiles and subclinical atherosclerosis, with potentially important implications for atherosclerosis prevention in modernizing China.

A Tale of Three Gorges in the Yangtze River: Comparing the Prevalence of Metabolic Syndrome According to ATPIII, WHO, and IDF Criteria and the Association with Vascular Health in Modernizing China.

BACKGROUND: Metabolic syndrome (MS) is associated with atherosclerotic diseases. The prevalence of MS according to the Adult Treatment Panel III (ATPIII), World Health Organization (WHO), and International Diabetes Federation (IDF) criteria are variable but increasing in western countries and modernizing China. This study aimed to evaluate the prevalence of MS according to these three criteria, in farmers or ex-farming residents in three-gorges territories undergoing rapid lifestyle changes. METHODS: We compared 95 residents (ex-farmers) in Wu Shan (WS) (28.4% men, aged 49.7 ± 9 years) resettled uphill for 3-5 years, and 87 age- and gender-matched farmers in Da Chang (DC) (27.6% men, aged 48.8 ± 10 years) before migration. MS and other traditional risk factors were assessed and carotid intima-media thickness (IMT) measured. RESULTS: Ninety-nine percent of WS residents were retired or adopted nonfarming jobs. Compared with DC farmers, WS ex-farmers had higher waist circumference, low density lipoprotein-cholesterol, and triglycerides (P < 0.0001), but their blood pressures, HDL-cholesterol, and fasting glucose were similar. MS were identified in 43.2% (IDF), 36.8% (WHO), and 29.5% (ATPIII) respectively in WS ex-farmers, compared with 17.2%, 13.8%, and 11.5% respectively in DC farmers. Carotid IMT was significantly higher in WS ex-farmers (0.74 ± 0.16 mm) than in DC farmers (0.64 ± 0.11 mm) (P < 0.0001). On multivariate regression analysis, prevalence of MS was correlated with job nature (beta = 0.425, P < 0.0001). Carotid IMT was better correlated with IDF MS criteria (beta = 0.208, P = 0.021), independent of age and WS location (regression adjusted R2 = 0.444, F-value 12.0, P < 0.0001), but not with the ATPIII or WHO criteria. CONCLUSIONS: IDF MS criteria is more sensitive, better correlates with atherosclerosis surrogate, and accordingly is more readily applicable to modernizing China.

Brief Report: Progression of Atherosclerosis in HIV-Infected Individuals-Prospective Data From an Asian Cohort.

BACKGROUND: The magnitude and risk factors of progression of atherosclerosis in Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1) the rate of progression of atherosclerosis in HIV-infected individuals, and (2) metabolic and inflammatory parameters that may predict atherosclerosis progression in HIV-infected individuals in an Asian cohort. SETTING: A prospective, longitudinal study was performed among adults attending an HIV Metabolic clinic in Hong Kong. METHODS: Carotid intima media thickness (cIMT) was measured at baseline and 24 months. Body composition, metabolic, and inflammatory biomarkers [including homeostasis model assessment of insulin resistance, LDL (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive protein, adiponectin] associated with cIMT change were analyzed; their predictive performances were estimated using receiver operating characteristic analyses. RESULTS: Sixty-one HIV-infected individuals (mean ± SD age 49.8 ± 11.4 years, 89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were recruited. Annual rate of change of cIMT was +0.0075 (0.0000-0.0163) mm/yr, and 19% developed new plaque at 24 months. Two patients died during the study period, 1 because of sudden cardiac death. Using receiver operating characteristic analyses, combination of lower limb fat percentage, LDL cholesterol subclass pattern B, and lower adiponectin level, but not Framingham score, predicted greater cIMT progression in HIV-infected individuals. CONCLUSIONS: Asian HIV-infected individuals had atherosclerosis progression. Limb fat percentage, LDL cholesterol particle size, and adiponectin level may identify at-risk Asian HIV-infected individuals for early intervention.

Effects of resistance training on cardiovascular health in non-obese active adolescents.

AIM: To determine the benefits of a 10-wk resistance training programme on cardiovascular health in non-obese and active adolescents. METHODS: This is a pragmatic randomised controlled intervention. The study was carried out in a Hong Kong Government secondary school. Thirty-eight lean and active boys and girls were randomised to either the resistance training group or the control group. Students in the resistance training group received in-school 10-wk supervised resistance training twice per week, with each session lasting 70 min. Main outcome measures taken before and after training included brachial endothelial dependent flow-mediated dilation, body composition, fasting serum lipids, fasting glucose and insulin, high sensitive C-reactive protein, 24-h ambulatory blood pressure and aerobic fitness. RESULTS: The only training related change was in endothelial dependent flow-mediated dilation which increased from 8.5% to 9.8%. A main effect of time and an interaction (P < 0.005) indicated that this improvement was a result of the 10-wk resistance training. Main effects for time (P < 0.05) in a number of anthropometric, metabolic and vascular variables were noted; however, there were no significant interactions indicating the change was more likely an outcome of normal growth and development as opposed to a training effect. CONCLUSION: Ten weeks of resistance training in school appears to have some vascular benefit in active, lean children.

Effects of diet and exercise on obesity-related vascular dysfunction in children.

BACKGROUND: The prevalence of obesity in both adults and children is increasing rapidly. Obesity in children is independently associated with arterial endothelial dysfunction and wall thickening, key early events in atherogenesis that precede plaque formation. METHODS AND RESULTS: To evaluate the reversibility of obesity-related arterial dysfunction and carotid intima-media thickening by dietary and/or exercise intervention programs, 82 overweight children (body mass index, 25+/-3), 9 to 12 years of age, were randomly assigned to dietary modification only or diet plus a supervised structured exercise program for 6 weeks and subsequently for 1 year. The prospectively defined primary end points were ultrasound-derived arterial endothelial function (endothelium-dependent dilation) of the brachial artery and intima-media thickness of common carotid artery. At 6 weeks, both interventions were associated with decreased waist-hip ratio (P<0.02) and cholesterol level (P<0.05) as well as improved arterial endothelial function. Diet and exercise together were associated with a significantly greater improvement in endothelial function than diet alone (P=0.01). At 1 year, there was significantly less thickening of the carotid wall (P<0.001) as well as persistent improvements in body fat content and lipid profiles in the group continuing an exercise program. Vascular function was significantly better in those children continuing exercise (n=22) compared with children who withdrew from the exercise program (n=19) (P<0.05). CONCLUSIONS: Obesity-related vascular dysfunction in otherwise healthy young children is partially reversible with diet alone or particularly diet combined with exercise training at 6 weeks, with sustained improvements at 1 year in those persisting with diet plus regular exercise.

Deleterious impact of "high normal" glucose levels and other metabolic syndrome components on arterial endothelial function and intima-media thickness in apparently healthy Chinese subjects: the CATHAY study.

OBJECTIVE: Endothelial vasodilator dysfunction and carotid intima-media thickening are useful surrogate markers of cardiovascular disease, a major cause of morbidity and mortality in type 2 diabetic patients. However, because most studies reporting the relationships between endothelial function, intima-media thickness (IMT), and hyperglycemia have compared diabetic patients with healthy controls, we report their relationship with glycemia as a continuum. METHODS AND RESULTS: Brachial artery endothelial function (flow-mediated dilatation [FMD]) and carotid IMT were measured noninvasively by high-resolution ultrasound B-mode imaging in 228 apparently healthy Chinese subjects recruited from Hong Kong and Macau. FMD and IMT were significantly associated with increasing levels of glycemia, particularly in the "high normal" glycemic range, with IMT increasing and endothelium-independent dilatation decreasing linearly across the glucose tertiles, and endothelium-dependent dilatation significantly lower in the upper glucose tertile compared with the other 2 groups (P<0.01). Using multiple linear regression, fasting glucose level was identified as an independent predictor of each of these markers of vascular function (P<0.004). Additionally, other conventional cardiovascular risk factors, including obesity, blood pressure, and an adverse lipid profile, were also related to levels of glycemia (P<0.05), further contributing to impaired vascular function. CONCLUSIONS: Increasing levels of glycemia and the coexistence of other cardiovascular risk factors in apparently healthy subjects are adversely associated with arterial endothelial dysfunction and intima-media thickening.

Endothelial function in children with OSA and the effects of adenotonsillectomy.

BACKGROUND: The association between childhood OSA and endothelial function as measured by flow-mediated dilation (FMD) and its response to OSA treatment are uncertain. The objective of this study was to compare FMD in children with OSA with nonsnoring control subjects and to examine its response to treatment. METHODS: Index cases were children aged 6 to 18 years with habitual snoring and polysomnography (PSG)-confirmed OSA (obstructive apnea hypopnea index [OAHI] > 1 events/h). Each case was paired with an age-, sex-, and BMI-matched nonsnoring control subject recruited from our previous community growth survey. All subjects underwent FMD measurement in the morning after overnight PSG. Adenotonsillectomy (AT) was offered to subjects who satisfied predefined AT operation criteria. All cases underwent repeat PSG and FMD assessment 6 months later. RESULTS: A total of 63 case-control pairs were recruited. The OSA group had a significantly higher OAHI (median, 5.3 events/h [interquartile range (IQR), 2.6-11.7] vs 0.2 events/h [IQR, 0-0.5], P < .001) and lower FMD (mean ± SD, 7.9% ± 1.3% vs 8.3% ± 0.8%; P = .04) than the control group. Thirty-two case subjects underwent AT. A significant reduction in OAHI was documented in the AT group (-8.8 events/h [IQR, -13.7 to -4.7]; P < .001) accompanied by a significant increase in FMD (+0.6% [IQR, 0.4-1.4]; P < .001), which was not observed in subjects who did not undergo AT. CONCLUSIONS: Children with OSA had reduced FMD, which was reversible with treatment.

Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation.

PURPOSE: Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with endothelial dysfunction that can be improved with short-term folic acid supplementation. The current study aimed to assess whether folic acid supplementation could produce longer-term improvements in homocysteine levels and arterial endothelial function. SUBJECTS AND METHODS: Twenty-nine healthy adults with hyperhomocysteinemia were selected from 89 volunteers enrolled in a community-based atherosclerosis screening project. All subjects were given folic acid (10 mg/d) for 1 year. Fasting plasma homocysteine levels were measured by high-performance liquid chromatography. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound. RESULTS: Folic acid supplementation for 1 year was associated with a significant increase in mean (+/-SD) plasma folate levels (24 +/- 5 nmol/L to 40 +/- 5 nmol/L; P < 0.001) and a significant decline in homocysteine levels (9.0 +/- 1.7 micromol/L to 7.9 +/- 2.0 micromol/L; P < 0.001). Flow-mediated dilation also improved significantly, from 7.4% +/- 2.0% to 8.9% +/- 1.5% (P <0.0001), but there was no change in nitroglycerin-induced (endothelium-independent) responses. CONCLUSIONS: These results demonstrate that long-term folic acid improves arterial endothelial function and has potential implications for the prevention of atherosclerosis in adults with hyperhomocysteinemia.

A randomized placebo controlled trial of an innovative herbal formula in the prevention of atherosclerosis in postmenopausal women with borderline hypercholesterolemia.

BACKGROUND: Danshen (Salvia miltiorrhiza) and Gegen (Radix puerariae) (D&G) are two herbs frequently used for the treatment of angina and other cardiac symptoms in Chinese materia medica. Recent studies have demonstrated their cardio-protective and anti-atherosclerosis effects. Earlier we have conducted two clinical trials in 2004 and 2007 which demonstrated such effects in extremely high risk patients. STUDY OBJECTIVE: The aim of the study was to demonstrate the safety and effectiveness of D&G in the prevention of atherosclerosis in postmenopausal women with early hypercholesterolemia. DESIGN: The study was designed as a randomized, double-blinded, placebo-controlled trial with a 12-month treatment period. SUBJECT: A population based sample of 165 postmenopausal women aged 47-65 were included in the trial. Only women who experienced menopause for more than 12 months were recruited. INTERVENTIONS: The eligible subjects were randomized to take the D&G preparation (two capsules), or image-identical placebo capsules (two capsules) daily, in a double-blind and parallel fashion for 12 month. MEASUREMENTS: The postmenopausal women with mild hypercholesterolemia (mean age 56.5 ± 4.1 of treatment group and 56.0 ± 3.8 years of placebo group) were randomized to the D&G group or placebo group for trial treatment. Carotid intima-media thickness (IMT) was used as the surrogate marker and was measured using high resolution ultrasound. Lipid profile was also tested. RESULTS: Baseline characteristics were comparable between the two groups. After 12 months, there were no significant changes in the blood pressures and general biochemical profiles in both groups, however, there was a remarkable decrease in serum low density lipoprotein (LDL) cholesterol (-6.92%) and total cholesterol (TC) (-5.85%) in the D&G group compared with the placebo group (-3.21% and -3.42%) when compared with the baseline. The carotid intima-media thickness (IMT) decreased 1.52% from baseline in the D&G group (p < 0.004) but the decrease was only 1.13% in the placebo treatment group (p = 0.009) after 12 months treatment. Twelve adverse events were reported (six in placebo group and six in D&G group) but none of them was directly relevant to the study herbal preparation. CONCLUSIONS: Postmenopausal women with early hypercholesterolemia tolerated D&G well. D&G improved the carotid intima thickness, lowered LDL and total cholesterol. D&G therefore can be recommended for the prevention of atherosclerosis in postmenopausal women with hypercholesterolemia.

Ten years' research on a cardiovascular tonic: a comprehensive approach-from quality control and mechanisms of action to clinical trial.

Objective. Mortality arising from cardiovascular pathologies remains one of the highest. Maintenance of cardiovascular health therefore remains a universal concern. Interventional therapies and medications have made impressive advances, but preventive measures would be of the same importance. Method. Ten years' search for a simple herbal formula has resulted in a two-herb combination, consisting of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix. The formula has been studied extensively on cardiovascular biological platforms and then put on three clinical trials. Results. In the laboratory, the formula was found to have the biological effects of anti-inflammation, anti-oxidation, anti-foam cell formation on vascular endothelium, and vasodilation. Clinical trials using ultrasonic carotid intima thickness as a surrogate marker showed very significant benefits. No significant adverse effects were encountered. Conclusion. It is therefore recommended that the herbal formula could be used as an adjuvant therapy in cardiac patients under treatment or as a preventive agent among the susceptible.

Association between metabolic syndrome and carotid atherosclerosis: a community-based study in Hong Kong.

BACKGROUND: Carotid atherosclerosis should not be neglected as a cause for stroke in China, despite its low prevalence. This study was performed to evaluate the association between ultrasonographic markers for different stages of carotid atherosclerosis and metabolic syndrome. METHODS: This was a community-based study in Hong Kong. Metabolic syndrome was defined as having three or more of the following conditions or receiving specific treatment for these conditions: Abdominal obesity, elevated triglycerides, low high-density lipoprotein cholesterol, hypertension, and impaired fasting blood glucose. All subjects underwent carotid duplex ultrasonography. Mean carotid intima media thickness (CIMT) of bilateral common carotid arteries was used as the CIMT value for a single subject. CIMT within the 4(th) quartile was regarded as increased CIMT. Carotid plaque was defined as a focal CIMT of >1.5 mm. A carotid plaque obstructing ≥50% of vessel lumen was considered as carotid stenosis. RESULTS: A total of 653 subjects (mean age 55.1±10.4; 47.2% male) were recruited. Metabolic syndrome was found in 188 (28.8%) subjects (30.8% in males and 27.0% in females). Mean CIMT was 0.74±0.12 mm. Increased CIMT, carotid plaque, and carotid stenosis were detected in 163 (25.0%), 95 (14.5%), and 6 (1.4%) subjects, respectively. In multivariate linear regression, CIMT significantly increased with increasing numbers of metabolic syndrome components (P<0.001). In multivariate logistic regression analysis, metabolic syndrome was independently associated with increased CIMT [odds ratio (OR) 1.17; 95% confidence interval (CI) 1.11-2.64; P=0.014), but not presence of carotid plaque (OR 1.50; 95% CI 0.92-2.46; P=0.108). CONCLUSIONS: Metabolic syndrome may be independently associated with the early stage but not the later and advanced stages of carotid atherosclerosis in community residents in China.