A Potential Strategy for Atherosclerosis Prevention in Modernizing China - Hyperhomocysteinemia, MTHFR C677T Polymorphism and Air Pollution (PM2.5) on Atherogenesis in Chinese Adults.

BACKGROUND: Atherosclerosis is one of the most important global health hazards and air pollution (AP, PM2.5) has been implicated. In addition to traditional risk factors hyperhomocysteinemia (HC) has been recognized in many parts of China related to risk of stroke. METHODS: To evaluate the impact of HC (homocysteine >14µmol/l) and PM2.5 air pollution on atherogenesis in modernizing China, we studied 756 asymptomatic Chinese in China from 1998-2007. PM2.5 exposure, HC, folate, and methylenetetrahydrofolate reductase (MTHFR) C/T genotype were evaluated. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. Locations were categorized as zones 1, 2 and 3, with increasing PM2.5 exposure. RESULTS: HC was higher (19.4±13.1 and 27.1±25.1µmol/l) in high PM2.5-polluted zones 2 and 3 than in zone 1 (9.7±4.5µmol/l, p<0.0015). The top HC tertile was characterized by lower folate and vitamin B12, but a higher proportion of the MTHFR TT genotype, Metabolic Syndrome (MS) and PM2.5 level (p=0.0018). FMD was significantly lower (7.3±2.3%) and carotid IMT thicker (0.63±0.12mm) in the top HC tertile, compared with low HC tertile (8.4±2.5%, p<0.0001; 0.57±0.1mm, p<0.0001 respectively). Similar differences in FMD and IMT were seen in zones 2 and 3, compared with zone 1 (p<0.0001). On multivariate regression, HC was related to male gender (beta=0.106, p=0.021), MTHFR-TT (beta=0.935, p<0.0001), locations (beta=0.230, p<0.0001) and folate-MTHFR interaction (beta=-0.566, p<0.0001). FMD was related to age (beta= -0.221; p<0.0001), male gender (beta= -0.194, p=0.001) PM2.5 and location (beta=-0.285 to -0.303, p<0.0001). Carotid IMT was related to PM2.5 (beta=0.173, p<0.0001), HC (0.122, p=0.006) but not to MTHFR or location, independent of age, gender, MS, and LDL-C. No significant HC-PM2.5 interaction effect on FMD and IMT was observed. CONCLUSION: HC and PM2.5 pollution but not MTHFR genotype were both related to carotid IMT, independent of other traditional risk factors. This has potential implications in dietary and AP strategies for atherosclerosis prevention in China.

Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

Vitamins B-12 and C Supplementation Improves Arterial Reactivity and Structure in Passive Smokers: Implication in Prevention of Smoking-Related Atherosclerosis.

BACKGROUND: Atherosclerosis is an important medical problem of modern society. High environmental tobacco smoke in casino is associated with an accelerated atherogenic process. We have previously shown vitamin B12 and C supplementation improves vascular reactivity and may be beneficial in vascular protection. OBJECTIVE: To evaluate the impact of vitamin supplementation on atherosclerosis (brachial artery reactivity FMD and carotid intima-media thickness IMT) in subjects exposed to high environmental tobacco smoke. DESIGN: Double-blind 2x2 factorial design fashion. SETTING: Computer randomization in 4 treatment groups: placebo (n=24), vitamin B12 (n=21), vitamin C (n=23) and vitamin B12+C (n=23) groups. PARTICIPANTS: 91 passive-smoking casino employees (19.2% male, mean age 45.0±8.2 years). INTERVENTION: Subjects were randomized to receive vitamin B12 (500µg daily), vitamin C (200mg daily), vitamin B12+C or image-matched placebo capsules for 1 year. MEASUREMENT: Brachial FMD and carotid IMT (surrogate atherosclerotic markers) were measured by ultrasound at baseline and on completion at 12 months. METHODS: 91 passive smoking casino employees (19.2% male, mean age 45.0±8.2 years) were randomized to receive vitamin B12 (500µg daily), vitamin C (200mg daily), vitamin B12+C or image-matched placebo capsules in double-blind 2 x 2 factorial design fashion for 1 year. Brachial FMD and carotid IMT (surrogate atherosclerotic markers) were measured by ultrasound at baseline and 12 months. RESULTS: Of the 78 (85.7%) passive-smoking employees completed the study, 11.5% had hypertension, 5.1% diabetes mellitus and 15.4% hypercholesterolemia. There were no significant changes in their blood pressures, lipid profiles, glucose and body mass index after supplementation for 1 year, but mild decrease in DBP (p<0.001) and blood creatinine (p<0.01) after combined vitamin B12 and C, and significant increase in blood B12 after vitamin B12 (p<0.01) and vitamin B12+C supplementations (p<0.001). Brachial FMD and cartotid IMT improved after the 3 vitamin supplementations (p<0.001), but not after placebo, being more significant after combined vitamin supplementations (p<0.0001). No adverse effects were reported. CONCLUSION: Vitamin B12 or C supplementation in passive smokers improved vascular reactivity and structures at 1 year, with implication in long term atherosclerosis prevention.

The impact of particulate matter air pollution (PM2.5) on atherosclerosis in modernizing China: a report from the CATHAY study.

BACKGROUND: Air pollution has been associated with an increase in cardiovascular diseases incidence. To evaluate whether air pollution can accelerate atherogenic processes, we assessed the effects of air pollution on important surrogate markers of atherosclerosis [brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT)]. METHODS: A total of 1656 Han Chinese (mean age 46.0 + 11.2 years; male 47%) in Hong Kong, Macau, Pun Yu, Yu County and the 3-Gorges Territories (Yangtze River) were studied between 1996 and 2007 [Chinese Atherosclerosis in the Aged and Young Project (the CATHAY Study)]. Cardiovascular risk profiles were evaluated. Particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) parameters were computed from satellite sensors. Brachial FMD and carotid IMT were measured by ultrasound. RESULTS: Health parameters [age, gender, body mass index, waist : hip ratio (WHR) and glucose)] were similar in lowest and highest PM2.5 exposure tertiles, systolic and diastolic blood pressures and triglycerides were higher (P < 0.001) and low-density cholesterol (LDL-C) was lower in the top PM2.5 tertile (P < 0.001). Brachial FMD [7.84 ± 1.77, 95% confidence interval (CI) 7.59-8.10%, vs 8.50 ± 2.52, 95% CI 8.23-8.77%, P < 0.0001) was significantly lower and carotid IMT (0.68 ± 0.13 mm, 95% CI 0.67-0.69 mm vs 0.63 mm ± 0.15 mm 95% CI 0.62-0.64 mm; P < 0.0001) was significantly thicker in the top PM2.5 tertile compared with the lowest tertile. On multiple regression, FMD was inversely related to PM2.5 (beta = 0.134, P = 0.015) independent of gender, age and blood pressure (model R2 = 0.156, F-value = 7.6, P < 0.0001). Carotid IMT was significantly correlated with PM2.5 exposure (beta = 0.381, P < 0.0001) independent of age, location, gender, WHR, blood pressure and LDL-C (model R2 = 0.408, F-value = 51.4, P-value <0.0001). CONCLUSIONS: Air pollution is strongly associated with markers of early atherosclerosis, suggesting a potential target for preventive intervention.

Plasma beta-globin DNA as a prognostic marker in chest pain patients.

BACKGROUND: Acute coronary syndrome may involve cell death and the release of nucleic acids into the circulation. We thus investigated whether plasma DNA concentrations are increased and determined its prognostic significance in patients with ACS. METHODS: Real-time polymerase chain reaction was used to quantitatively measure the beta-globin gene from blood samples taken from patients presenting to an emergency department with chest pain of probable cardiac cause. RESULTS: Samples from 58 patients with chest pain, and from 21 age- and sex-matched healthy control subjects were analysed. Compared with the control group, median plasma DNA concentrations were increased 1.5-fold in patients with minor cardiac injury, were increased further in patients with STEA and STEMI, and were the highest in those patients who died within 2 years (P=0.0005; post-hoc Dunn's, P<0.05). Median plasma DNA concentrations were higher in patients who later developed heart failure (1060 vs. 500 kGE/l; P=0.0095); higher in patients who later reinfarcted (1000 vs. 530 kGE/l; P=0.0298); higher in patients who had a cardiac arrest in that admission (1350 vs. 525 kGE/l; P=0.04); and were higher in patients who were readmitted within 6 months of discharge (725 vs. 475 kGE/l; P=0.04). CONCLUSION: Plasma DNA is a potential marker for post-ACS complications.

Factors associated with healthcare utilization costs for statin therapy--a pilot study in Hong Kong.

BACKGROUND: Socio-economic status, comorbidities and adherence to statin therapy might affect the cost-effectiveness of statin therapy in hyperlipidemia. OBJECTIVE: To examine the effects size of demographic factors, clinical factors and adherence to statin therapy on the direct medical costs for Chinese patients at high risk of coronary heart disease (CHD). METHODS: This was a prospective, observational cohort study conducted in the outpatient departments of a public teaching hospital in Hong Kong. Patients at high risk of CHD who had been on statin monotherapy for < 12 months were recruited. Baseline demographic and clinical data were obtained. Statin adherence was monitored prospectively over 6 months using the Medication Event Monitoring System. Total direct medical costs per member per month (cPMPM), including cost for clinic visits, statin medication, laboratory tests on lipids and management of CHD events if any, were calculated from the perspective of a public healthcare organization. RESULTS: 83 patients completed the study. Median cPMPM in 80 patients (96% of 83 patients) without a new CHD event (USD 42) and for 3 (4%) patients who experienced CHD events (USD 444) were significantly different (p = 0.003). History of congestive heart failure (beta = 1,957, 95% CI = 1,006 - 2,909), male gender (beta = 584, 95% CI = 215 - 952), coronary atherosclerosis (beta = 1,436, 95% CI = 538 - 2,334) and diabetes mellitus (beta = 604, 95% CI = 136 - 1,07 1) were positive predictors for cPMPM. CONCLUSION: In this pilot study male gender, diabetes mellitus, congestive heart failure and coronary atherosclerosis appear to be significantly associated with higher costs for Chinese patients at high risk of CHD.

Antecedent risk factors and their control in young patients with a first myocardial infarction.

INTRODUCTION: Identifying and controlling cardiovascular risk factors at an early age may prevent cases of young myocardial infarction (MI). We studied age-related differences in the cumulative incidence of risk factors and the adequacy of primary prevention by surveying 1,556 patients with a first MI admitted to a tertiary hospital in Singapore. METHODS: This is a single centre registry-based study on patients admitted with a first MI to a tertiary hospital in Singapore. We stratified the cohort into younger (45 years of age and younger) and older (older than 45 years of age) groups. The presence of five risk factors, namely: hypertension, diabetes mellitus (DM), smoking, a family history of premature MI, and hyperlipidaemia, was assessed at the point of care by interview and prior medical records when obtainable. We also determined by the same methods, if these patients were receiving active treatment for DM, hypertension or hyperlipidaemia prior to their first MI. Lipid levels were measured within 24 hours of admission. RESULTS: 96 percent of patients 45 years and younger and 92 percent of those older than 45 years had at least one antecedent risk factor. The 45 years and younger age group had a higher incidence of untreated hypertension (odds ratio 2.99, 95 percent confidence interval 2.00-4.46, p-value is less than 0.001) and hyperlipidaemia (odds ratio 1.71, 95 percent confidence interval 1.20 - 2.43, p-value is equal to 0.002). CONCLUSION: A majority of young patients with a first MI have at least one identifiable antecedent risk factor. There is significant undertreatment of hypertension and hyperlipidaemia in this age group.

The impact of heavy passive smoking on arterial endothelial function in modernized Chinese.

OBJECTIVES: The study evaluated whether heavy exposure to environmental tobacco smoke (passive smoking) might damage arterial function in modernized Chinese. BACKGROUND: Heavy passive smoking is associated with arterial endothelial dysfunction in Caucasian, but not rural Chinese, subjects. METHODS: We studied 20 young (mean age 36.6 +/- 7.0 years) nonsmoking asymptomatic casino workers (9 men) in Macau who were exposed to environmental tobacco smoke for over 8 h/day for at least two years and 20 normal subjects (control subjects). These two groups were carefully matched for age, gender, body mass index (BMI), blood pressure, vessel diameter, cholesterol and glucose levels. Brachial artery diameter was measured by high-resolution B-mode ultrasound at rest, after flow increase (causing flow-mediated endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator). RESULTS: Flow-mediated dilation (mean +/- SD% of diameter changes) was significantly lower in passive smokers (6.6 +/- 3.4%) compared with the controls (10.6 +/- 2.3%) (p < 0.0001). Nitroglycerin-induced dilation of the two groups were similar. Upon multivariate analysis, passive smoking exposure was the strongest independent predictor (beta = -0.59; p = 0.0001) for impaired flow-mediated endothelium-dependent dilation (model R2 = 0.75, F value = 6.1, p = 0.0001). CONCLUSIONS: In modernized Chinese, as in Caucasians, exposure to heavy environmental tobacco smoke causes arterial endothelial dysfunction, a key early event in atherosclerosis. This may have serious implications for cardiovascular health in China, currently in a process of rapid modernization.

Folic acid improves arterial endothelial function in adults with hyperhomocystinemia.

OBJECTIVES: To evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia. BACKGROUND: Hyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known. METHODS: Adults subjects were recruited from a community-based atherosclerosis study on healthy volunteers aged 40 to 70 years who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis (n = 89). Seventeen subjects (aged 54 +/- 10 years, 15 male) with fasting total homocystine levels above 75th percentile (mean, 9.8 +/- 2.8 micromol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each subject received oral folic acid (10 mg/day) and placebo for 8 weeks, each separated by a washout period of four weeks. Flow-mediated endothelium-dependent dilation (percent increase in diameter) of the brachial artery was assessed by high resolution ultrasound, before and after folic acid or placebo supplementation. RESULTS: Compared with placebo, folic acid supplementation resulted in higher serum folate levels (66.2 +/- 7.0 vs. 29.7 +/- 14.8 nmol/liter; p < 0.001), lower total plasma homocystine levels (8.1 +/- 3.1 vs. 9.5 +/- 2.5 micromol/liter, p = 0.03) and significant improvement in endothelium-dependent dilation (8.2 +/- 1.6% vs. 6 +/- 1.3%, p < 0.001). Endothelium-independent responses to nitroglycerin were unchanged. No adverse events were observed. CONCLUSION: Folic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process.

Chinese adults are less susceptible than whites to age-related endothelial dysfunction.

OBJECTIVES: We sought to assess the effects of aging on the endothelial physiology of a group of Chinese adults. BACKGROUND: Several studies have documented an association between aging and progressive arterial endothelial dysfunction in white subjects. We hypothesized that age-related endothelial dysfunction, an important event in atherosclerosis, might be less marked in southern Chinese subjects, in whom the prevalence of coronary heart disease is only approximately 20% of that in industrialized countries. METHODS: We studied endothelial function in 76 healthy adults aged 16 to 70 years: 38 Chinese from a village of 3,000 people in southern China and 38 white subjects from Sydney, Australia. In each ethnic group, there were 19 younger persons (16 to 40 years) and 19 older adults (55 to 70 years). None had evidence of diabetes, hypertension or clinical vascular disease or had ever been regular cigarette smokers. With the use of high resolution external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator). RESULTS: Endothelium-dependent dilation was similar in young Chinese (mean +/- SD 8.3 +/- 2.5%), young whites (7.9 +/- 2.0%) and older Chinese (6.8 +/- 2.9%), but it was significantly impaired in older whites (1.8 +/- 2.5%, p < 0.001 by analysis of variance). On multivariate analysis, older age was associated with impaired endothelium-dependent dilation (p < 0.001) (independent of the effects of serum cholesterol, gender and vessel size) in the white but not in the Chinese subjects (p = 0.83). Nitroglycerin-induced dilation was not significantly different with aging in either ethnic group. CONCLUSIONS: Endothelium-dependent dilation is similar in the arteries of healthy young Chinese and white adults. With older age, however, Chinese subjects are less susceptible to impaired endothelial function.

Beta-blockade in heart failure: a comparison of carvedilol with metoprolol.

OBJECTIVES: This study was performed to compare the long-term clinical efficacy of treatment with metoprolol versus carvedilol in patients with chronic heart failure. BACKGROUND: Beta-adrenergic blockade is of proven value in chronic heart failure. Metoprolol, a selective beta-blocker, is widely used, but recent trials suggest carvedilol, a nonselective beta-blocker with alpha-1-receptor antagonist activity and antioxidant activities, is also effective. It is uncertain, however, if these additional properties of carvedilol provide further clinical benefit compared with metoprolol. METHODS: In this randomized double-blind control trial, 51 patients with chronic heart failure and mean left ventricular (LV) ejection fraction of 26% +/- 1.8% were randomly assigned treatment with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy after a four-week dose titration period for a total of 12 weeks. Response was assessed by a quality of life questionnaire, New York Heart Association class, exercise capacity (6-min walk test), radionucleotide ventriculography for LV ejection fraction, two-dimensional echocardiography measurement of LV dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate variability. RESULTS: Both carvedilol and metoprolol produced highly significant improvement in symptoms (p < 0.001), exercise capacity (p < 0.05) and LV ejection fraction (p < 0.001), and there were no significant differences between the two drugs. Carvedilol had a significantly greater effect on sitting and standing blood pressure, LV end-diastolic dimension and normalized the mitral E wave deceleration time. CONCLUSIONS: Both metoprolol and carvedilol were equally effective in improving symptoms, quality of life, exercise capacity and LV ejection fraction, although carvedilol lowers blood pressure more than metoprolol.

Method of measuring charge distribution of nanosized aerosols.

In this paper, we present the development of a method to accurately measure the positive and negative charge distribution of nanosized aerosols using a tandem differential mobility analyzer (TDMA) system. From the series of TDMA measurements, the charge fraction of nanosized aerosol particles was obtained as a function of equivalent mobility particle diameter ranging from 50 to 200 nm. The capability of this new approach was implemented by sampling from a laminar diffusion flame which provides a source of highly charged particles due to naturally occurring flame ionization process. The results from the TDMA measurement provide the charge distribution of nanosized aerosols which we found to be in reasonable agreement with Boltzmann equilibrium charge distribution theory and a theory based upon charge population balance equation (PBE) combined with Fuchs theory (N.A. Fuchs, Geofis. Pura Appl. 56 (1963) 185). The theoretically estimated charge distribution of aerosol particles based on the PBE provides insight into the charging processes of nanosized aerosols surrounded by bipolar ions and electrons, and agree well with the TDMA results.

A single-blind, randomized, cross-over study of angiotensin-converting enzyme inhibitor and triamterene and hydrochlorothiazide in the treatment of mild to moderate hypertension in the elderly.

Forty patients over 70 years old with a diastolic blood pressure of 95 to 110 mm Hg and/or a systolic blood pressure of 170 to 220 mm Hg after two weeks' placebo therapy underwent a single-blind, placebo-controlled, randomized cross-over study using captopril and triamterene and hydrochlorothiazide (Dyazide). Blood pressure was lowered from a mean of 189 +/- 2.0/92 +/- 1.7 mm Hg (mean +/- SEM) to 161 +/- 2.8/78 +/- 1.7 mm Hg with captopril therapy, and therapy with triamterene and hydrochlorothiazide produced similar reductions (156 +/- 2.7/78 +/- 1.7 mm Hg). Two patients on triamterene and hydrochlorothiazide therapy withdrew because of side effects, while only minor side effects were observed with captopril therapy. Therapy with triamterene and hydrochlorothiazide produced significant elevation of urea, creatinine, and uric acid, while captopril therapy produced no biochemical or hematologic changes. A single daily dose of captopril alone was sufficient to normalize the blood pressure in 31 (75%) of 40 patients. Captopril appears to be a promising monotherapy for the elderly with mild to moderate hypertension.

Comparison of frequencies of left ventricular systolic and diastolic heart failure in Chinese living in Hong Kong.

There is a wide variation (13% to 74%) in the reported prevalence of heart failure associated with normal left ventricular (LV) systolic function (diastolic heart failure). There is no published information on this condition in China. To ascertain the prevalence of diastolic heart failure in this community, 200 consecutive patients with the typical features of congestive heart failure were studied with standard 2-dimensional Doppler echocardiography. A LV ejection fraction (LVEF) >45% was considered normal. The results showed that 12.5% had significant valvular heart disease. Of the remaining 175 patients, 132 had a LVEF >45% (75%). Therefore, 66% of patients with a clinical diagnosis of heart failure had a normal LVEF. Heart failure with normal LV systolic function was more common than systolic heart failure in those >70 years old (65% vs 47%; p = 0.015). Most (57%) had an abnormal relaxation pattern in diastole and 14% had a restrictive filling pattern. In the systolic heart failure group, a restrictive filling pattern was more common (46%). There were no significant differences in the sex distribution, etiology, or prevalence of LV hypertrophy between these 2 heart failure groups. In conclusion, heart failure with a normal LVEF or diastolic heart failure is more common than systolic heart failure in Chinese patients with the symptoms of heart failure. This may be related to older age at presentation and the high prevalence of hypertension in this community.

Lack of association between insertion/deletion polymorphism of the angiotensin-converting enzyme gene and end-stage heart failure due to ischemic or idiopathic dilate cardiomyopathy in the Chinese.

Homozygosity for the deletion allele of the angiotensin-converting enzyme gene (DD) has been associated with a variety of cardiovascular diseases, including ischemic and idiopathic dilated cardiomyopathy, in Caucasians. In this study of 104 Chinese patients with end-stage heart failure due to idiopathic dilated or ischemic cardiomyopathy, the DD genotype frequency was low (12% and 11%, respectively) and was not seen more often than in a control group of 183 subjects without cardiac disease (13%). Therefore, in the Chinese, the DD genotype is less common than in Caucasians and does not appear to be associated with the development of either ischemic or idiopathic dilated cardiomyopathy.

Transcranial Doppler evaluation of microembolism immediately after direct-current cardioversion for atrial fibrillation in anticoagulated patients.

Transcranial Doppler monitoring showed no evidence of microemboli for 10 minutes after direct-current cardioversion for atrial fibrillation.

Risk factors for acute myocardial infarction in a southern Chinese population.

Although the mortality rate from coronary artery disease in Hong Kong is only one-fourth of that of northern Europe and the United States, the disease has been and remains the second major cause of death (after all cancers combined). Beginning in 1987, we have conducted a case-control study of acute myocardial infarction in four Hong Kong hospitals. This study, one of the biggest case-control studies conducted in the Chinese population of both men and women, confirms the importance of several risk factors--cigarette smoking, history of hypertension, history of diabetes, body fatness, and lack of physical activity--previously described in data collected in western populations. In addition, more adverse childhood experience was also found to be an important risk factor of acute myocardial infarction. Further research in appropriate intervention measures in education in the prevention and cessation of smoking, the control of blood pressure, diabetes, and overweight, and adequate exercise could significantly help reduce the risk of acute myocardial infarction in the Hong Kong Chinese population.

Obstructive sleep apnea presenting with nocturnal angina, heart failure, and near-miss sudden death.

An obese woman with a one-year history of episodic nocturnal chest pain was admitted because of shock and pulmonary edema. A clinical diagnosis of acute myocardial infarction and cardiogenic shock was made. She was ventilated and successfully resuscitated. Subsequent investigations showed no evidence of cardiac dysfunction or coronary disease, but sleep study confirmed the diagnosis of obstructive sleep apnea syndrome (OSAS). We suggest that the nocturnal angina and heart failure in this patient might have resulted from extreme hypoxemia produced by OSAS. This case raised the possibility that the high cardiovascular mortality rate reported in OSAS might not necessarily relate to underlying coronary artery disease. Further investigations are required to delineate the true incidence of coronary disease in patients with OSAS.

Factors determining the maintenance dose of warfarin in Chinese patients.

Chinese patients are reportedly more sensitive than Caucasians to the anticoagulant effect of warfarin. We examined warfarin dose requirements and their determinants in 151 Chinese out-patients on stable maintenance dose of warfarin with international normalized ratio of 2 to 2.5. Mean daily warfarin requirement was 3.3 +/- 1.4 mg, much lower than reported doses in Caucasian patients. The most important determinant was age (r = -0.43, p < 0.001), with progressively lower warfarin requirement with increasing age (p = 0.0001). There was a weaker association with body weight (r = 0.20, p = 0.01). Patients with chronic rheumatic heart disease tended to require a smaller dose than those with heart valve replacements (2.94 +/- 1.24 vs. 3.69 +/- 1.42 mg, p < 0.01). We confirm that Chinese patients require a smaller dose of warfarin for the same degree of anticoagulation. Age is the most important factor affecting dose requirement, although body weight and underlying disease also play a role.