Plasma Protein Biomarkers and Long-Term Cardiovascular Mortality Risk in Patients With Chronic Coronary Heart Disease.

BACKGROUND: Protein biomarkers that reflect different pathophysiological pathways have been associated with the risk of adverse cardiovascular events. However, it is uncertain whether these associations are sustained with increasing years after the biomarkers are measured. METHODS AND RESULTS: In this cohort study, 7745 patients with coronary heart disease who participated in the LIPID (Long-Term Intervention With Pravastatin in Ischemic Disease) trial, BNP (B-type natriuretic peptide), troponin I, cystatin-C, C-reactive protein, d-dimer and midregional proadrenomedullin were measured at baseline and after 1 year. Discrimination of plasma biomarker concentrations for cardiovascular death were evaluated in landmark analyses from 1 year for the next 5 years of the randomized trial, and for 10 additional years after trial completion. All 6 biomarkers were associated with risk of cardiovascular death (n=1903) both during and after the clinical trial (each P<0.001). C-statistics for BNP were 0.706 and 0.704; cystatin-C, 0.686 and 0.693; troponin I, 0.686 and 0.689; C-reactive protein, 0.655 and 0.684; d-dimer, 0.670 and 0.679, and midregional adrenomedullin, 0.686 and 0.688, respectively. In multivariable models, adding all 6 biomarkers to models with clinical risk factors increased the C-statistic for cardiovascular death from 0.709 to 0.775 during the clinical trial, and from 0.713 to 0.751 during 10-year follow-up after the randomized trial (P<0.001 for both). CONCLUSIONS: In patients with chronic coronary heart disease, biomarkers that reflect different pathophysiological pathways are associated with the risk of cardiovascular death for at least the next 15 years.

Using electronic medical record data to assess chronic kidney disease, type 2 diabetes and cardiovascular disease testing, recognition and management as documented in Australian general practice: a cross-sectional analysis.

OBJECTIVES: To evaluate the capacity of general practice (GP) electronic medical record (EMR) data to assess risk factor detection, disease diagnostic testing, diagnosis, monitoring and pharmacotherapy for the interrelated chronic vascular diseases-chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease. DESIGN: Cross-sectional analysis of data extracted on a single date for each practice between 12 April 2017 and 18 April 2017 incorporating data from any time on or before data extraction, using baseline data from the Chronic Disease early detection and Improved Management in PrimAry Care ProjecT. Deidentified data were extracted from GP EMRs using the Pen Computer Systems Clinical Audit Tool and descriptive statistics used to describe the study population. SETTING: Eight GPs in Victoria, Australia. PARTICIPANTS: Patients were ≥18 years and attended GP ≥3 times within 24 months. 37 946 patients were included. RESULTS: Risk factor and disease testing/monitoring/treatment were assessed as per Australian guidelines (or US guidelines if none available), with guidelines simplified due to limitations in data availability where required. Risk factor assessment in those requiring it: 30% of patients had body mass index and 46% blood pressure within guideline recommended timeframes. Diagnostic testing in at-risk population: 17% had diagnostic testing as per recommendations for CKD and 37% for T2D. Possible undiagnosed disease: Pathology tests indicating possible disease with no diagnosis already coded were present in 6.7% for CKD, 1.6% for T2D and 0.33% familial hypercholesterolaemia. Overall prevalence: Coded diagnoses were recorded in 3.8% for CKD, 6.6% for T2D, 4.2% for ischaemic heart disease, 1% for heart failure, 1.7% for ischaemic stroke, 0.46% for peripheral vascular disease, 0.06% for familial hypercholesterolaemia and 2% for atrial fibrillation. Pharmaceutical prescriptions: the proportion of patients prescribed guideline-recommended medications ranged from 44% (beta blockers for patients with ischaemic heart disease) to 78% (antiplatelets or anticoagulants for patients with ischaemic stroke). CONCLUSIONS: Using GP EMR data, this study identified recorded diagnoses of chronic vascular diseases generally similar to, or higher than, reported national prevalence. It suggested low levels of extractable documented risk factor assessments, diagnostic testing in those at risk and prescription of guideline-recommended pharmacotherapy for some conditions. These baseline data highlight the utility of GP EMR data for potential use in epidemiological studies and by individual practices to guide targeted quality improvement. It also highlighted some of the challenges of using GP EMR data.

Circulating Cystatin C Is an Independent Risk Marker for Cardiovascular Outcomes, Development of Renal Impairment, and Long-Term Mortality in Patients With Stable Coronary Heart Disease: The LIPID Study.

Background Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long-term or is independent of renal function and other important biomarkers. Methods and Results Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow-up, 6 years) and long-term (median follow-up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR-creatinine, then GFR-creatinine-cystatin C). Over 6 years, in fully adjusted multivariable time-to-event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07-1.74; P=0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19-1.82; P<0.001). Over 16 years, the association of baseline cystatin C with coronary heart disease, cardiovascular, and all-cause mortality persisted (each P<0.001) and remained significant after adjustment for estimated GFR-creatinine-cystatin C. Cystatin C also predicted the development of chronic kidney disease for 6 years (odds ratio, 6.61; 95% CI, 4.28-10.20) independently of estimated GFR-creatinine and other risk factors. However, this association was no longer significant after adjustment for estimated GFR-creatinine-cystatin C. Conclusions Cystatin C independently predicted major cardiovascular events, development of chronic kidney disease, and cardiovascular and all-cause mortality. Prediction of long-term mortality was independent of improved estimation of GFR. Registration URL: https://anzctr.org.au; Unique identifier: ACTRN12616000535471.

Gaps in the Care of Familial Hypercholesterolaemia in Australia: First Report From the National Registry.

BACKGROUND: Familial hypercholesterolaemia (FH) is under-diagnosed and under-treated worldwide, including Australia. National registries play a key role in identifying patients with FH, understanding gaps in care and advancing the science of FH to improve care for these patients. METHODS: The FH Australasia Network has established a national web-based registry to raise awareness of the condition, facilitate service planning and inform best practice and care services in Australia. We conducted a cross-sectional analysis of 1,528 FH adults enrolled in the registry from 28 lipid clinics. RESULTS: The mean age at enrolment was 53.4±15.1 years, 50.5% were male and 54.3% had undergone FH genetic testing, of which 61.8% had a pathogenic FH-causing gene variant. Only 14.0% of the cohort were family members identified through cascade testing. Coronary artery disease (CAD) was reported in 28.0% of patients (age of onset 49.0±10.5 years) and 64.9% had at least one modifiable cardiovascular risk factor. The mean untreated LDL-cholesterol was 7.4±2.5 mmol/L. 80.8% of patients were on lipid-lowering therapy with a mean treated LDL-cholesterol of 3.3±1.7 mmol/L. Among patients receiving lipid-lowering therapies, 25.6% achieved an LDL-cholesterol target of <2.5 mmol/L without CAD or <1.8 mmol/L with CAD. CONCLUSION: Patients in the national FH registry are detected later in life, have a high burden of CAD and risk factors, and do not achieve guideline-recommended LDL-cholesterol targets. Genetic and cascade testing are under-utilised. These deficiencies in care need to be addressed as a public health priority.

Results of the first recorded evaluation of a national gestational diabetes mellitus register: Challenges in screening, registration, and follow-up for diabetes risk.

OBJECTIVE: Gestational Diabetes Mellitus (GDM) increases the risk of type 2 diabetes. A register can be used to follow-up high risk women for early intervention to prevent progression to type 2 diabetes. We evaluate the performance of the world's first national gestational diabetes register. RESEARCH DESIGN AND METHODS: Observational study that used data linkage to merge: (1) pathology data from the Australian states of Victoria (VIC) and South Australia (SA); (2) birth records from the Consultative Council on Obstetric and Paediatric Mortality and Morbidity (CCOPMM, VIC) and the South Australian Perinatal Statistics Collection (SAPSC, SA); (3) GDM and type 2 diabetes register data from the National Gestational Diabetes Register (NGDR). All pregnancies registered on CCOPMM and SAPSC for 2012 and 2013 were included-other data back to 2008 were used to support the analyses. Rates of screening for GDM, rates of registration on the NGDR, and rates of follow-up laboratory screening for type 2 diabetes are reported. RESULTS: Estimated GDM screening rates were 86% in SA and 97% in VIC. Rates of registration on the NGDR ranged from 73% in SA (2013) to 91% in VIC (2013). During the study period rates of screening at six weeks postpartum ranged from 43% in SA (2012) to 58% in VIC (2013). There was little evidence of recall letters resulting in screening 12 months follow-up. CONCLUSIONS: GDM Screening and NGDR registration was effective in Australia. Recall by mail-out to young mothers and their GP's for type 2 diabetes follow-up testing proved ineffective.

Rural smokers - a prevention opportunity.

BACKGROUND: Smoking is the largest single cause of preventable death and disease in Australia. This study describes smoking prevalence and the characteristics of rural smokers to guide general practitioners in targeting particular groups. METHODS: Cross sectional surveys in the Greater Green Triangle region of southeast Australia using a random population sample (n=1563, participation rate 48.7%) aged 25-74 years. Smoking information was assessed by a self administered questionnaire. RESULTS: Complete smoking data were available for 1494 participants. Overall age adjusted current smoking prevalence was 14.9% (95% CI: 13.1-16.7). In both genders, current smoking prevalence decreased with age. Those aged 25-44 years were more likely to want to stop smoking and to have attempted cessation, but less likely to have received cessation advice than older smokers. DISCUSSION: This study provides baseline smoking data for rural health monitoring and identifies intervention opportunities. General practice is suited to implement interventions for smoking prevention and cessation at every patient encounter, particularly in younger individuals.royal, australian, college, general, practitioner, gp, doctor, medical, practice, racgp, health, care, medication, information, practitioners, family, physician, 2009, AFP, May, sleep, rural, smokers, prevention

Chronic disease risk factors in rural Australia: results from the Greater Green Triangle risk factor surveys.

The aim of this article was to assess the level and prevalence of major chronic disease risk factors among rural adults. Two cross-sectional surveys were carried out in 2004 and 2005 in the southeast of South Australia and the southwest of Victoria. Altogether 891 randomly selected persons aged 25 to 74 years participated in the studies. Surveys included a self-administered questionnaire, physical measurements, and a venous blood specimen for lipid analyses. Two thirds of participants had cholesterol levels>or=5.0 mmol/L. The prevalence of high diastolic blood pressure (>or=90 mm Hg) was 22% for men and 10% for women in southeast of South Australia, and less than 10% for both sexes in southwest of Victoria. Two thirds of participants were overweight or obese (body mass index>or=25 kg/m2). About 15% of men and slightly less women were daily smokers. The abnormal risk factor levels underline the need for targeted prevention activities in the Greater Green Triangle region. Continuing surveillance of levels and patterns of risk factors is fundamentally important for planning and evaluating preventive activities.

High density lipoprotein-cholesterol levels increase with age in American women but not in Hong Kong Chinese women.

OBJECTIVES: High-density lipoprotein (HDL) cholesterol is a powerful cardiovascular risk factor. Important gender and ethnic differences in plasma HDL levels exist and warrant investigation. DESIGN: Cross-sectional survey in two different general populations. Patients 7700 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2002 and 1944 participants of the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2) 2000-2004. MEASUREMENTS: Plasma HDL levels. RESULTS: Plasma HDL levels were higher in women than in men in both populations. In the United States women, it increased with age, whereas in Chinese women, it declined with age and converged with male HDL levels. In the United States, 37.1 +/- 1.2% men and 38.9 +/- 1.1% women had low HDL levels. In Hong Kong, 34.3 +/- 1.6% men and 34.5 +/- 1.5% women had low HDL levels. In Americans, the independent predictors of low HDL levels were lower age, being non-Mexican Hispanic, waist circumference, triglycerides and not drinking alcohol in men, and lower age, being Hispanic, waist circumference, triglycerides, current smoking and not drinking alcohol in women. In Hong Kong Chinese, the independent predictors of low HDL levels were body mass index, triglycerides, current smoking and not drinking alcohol in men, and lower age, waist circumference, triglycerides, diabetes and former smoking in women. CONCLUSIONS: The decline in plasma HDL with age in Chinese women is opposite to that seen in American women. The increased cardiovascular risk in elderly Chinese women requires further study.

Metabolic syndrome increases all-cause and vascular mortality: the Hong Kong Cardiovascular Risk Factor Study.

OBJECTIVE: The metabolic syndrome has been associated with increased mortality in some Caucasian populations, but data in Asian populations are not available. We present data describing the association of the metabolic syndrome with mortality. METHODS: The impact of the US National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) metabolic syndrome guidelines definition (using Asian central obesity criteria) on mortality was examined using Cox regression analyses in a population-based cohort (n = 2863) of Chinese subjects. RESULTS: The cohort was followed up for a mean duration of 8.45 years, a total of 24 101 person-years, with 89 deaths (33.7% of vascular origin). Compared to those without any component of the metabolic syndrome, following adjustment for age, socioeconomic status and a range of lifestyle habits, those with the metabolic syndrome had increased risk of both all-cause [hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.02-4.00, P for trend = 0.037] and vascular disease (HR 6.39, 95% CI 1.40-29.2, P < 0.05, P for trend = 0.002) mortality. When those with 0-2 components were compared to those with the metabolic syndrome, the HRs were 1.49 (95% CI 0.95-2.33, P = 0.084) and 3.36 (95% CI 1.57-7.19, P = 0.002), respectively. CONCLUSION: This study shows that the metabolic syndrome is associated with increased mortality risk in an Asian population. The high prevalence of the metabolic syndrome, particularly in the elderly, forewarns of a rapidly increasing problem in mainland China, and other Asian populations, which could have overwhelming public health ramifications.

Resistin gene polymorphisms and progression of glycaemia in southern Chinese: a 5-year prospective study.

OBJECTIVE: Human resistin gene (RETN) polymorphisms have been found to be associated with type 2 diabetes (T2DM), insulin resistance and/or obesity. We evaluated, in a 5-year prospective study, whether RETN polymorphisms could predict the progression of glycaemia in southern Chinese. DESIGN AND PATIENTS: We conducted a systematic search for variants in RETN in 70 southern Chinese subjects. This was followed by the genotyping in 624 unrelated nondiabetic subjects of two polymorphisms, -420C-->G and +62G-->A, previously reported in cross-sectional studies to be associated with T2DM in Asians, to examine their relationship with the progression of glycaemia in this cohort. RESULTS: We identified 15 polymorphisms, including 2 novel but rare polymorphisms (-319G-->A and +63G-->C). Compared to subjects with the CC genotype, -420GG subjects had higher 2-h glucose (7.7 +/- 1.8 vs. 7.2 +/- 2.0 mmol/l, P = 0.011) and insulin (101.6 +/- 69.5 vs. 79.8 +/- 59.5 mU/l, P = 0.021) during an oral glucose tolerance test. Carriers of the +62A allele had higher body mass indices (25.3 +/- 4.0 vs. 24.5 +/- 3.6 kg/m(2) in GG, P = 0.02). The presence of the allele -420G (OR 2.15, 95% CI 1.28-3.60, P = 0.004) or +62A (OR1.86, 95% CI 1.08-3.21, P = 0.025) predicted the progression of glycaemia at Year 5, after adjustment for sex, age or body mass index. The haplotype G-A also conferred a higher risk of progression in glycaemia (P = 0.002). CONCLUSION: Our study would support the role of the resistin gene in obesity, insulin resistance and progression of glycaemia in southern Chinese.

Subjective health and fibrinogen in a healthy Chinese cohort.

OBJECTIVES: This study explores standard cardiovascular (CVD) risk factors in a healthy population sample, with low CVD prevalence and presumed higher social connectedness as potential mechanisms linking subjective health (SH) and physical health. METHOD: A population-based, telephone-sampled, cross-sectional study recruited a healthy subset of 2280 Chinese adults who subsequently underwent a free medical examination. Serum total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, fibrinogen, fasting glucose, 2-hour post-load glucose, blood pressure and adiposity were compared between respondents reporting good SH and those reporting poor SH over the past 3 months, on a 4-point, single-item measure. RESULTS: After adjustment for age, gender, education, exercise, marital and smoking status, only serum fibrinogen significantly differentiated the two groups. Respondents reporting Very poor or Poor SH had a significantly greater likelihood of raised mean fibrinogen levels compared with those reporting Good or Very good SH (Adjusted Odds Ratio 1.37, 95% CL 1.002-1.84, p < .05). CONCLUSIONS: There is a small but robust association between SH and fibrinogen in this low CVD prevalent population unexplained by known pre-existing disease.

Smoking and perceived health in Hong Kong Chinese.

This population-based cross-sectional study examined the associations between smoking and perceived health in Hong Kong. 6117 healthy Chinese (3053 men, 3064 women), aged 25-74 years, were randomly selected for telephone interviews in Hong Kong in 1994-96. Adjusted odds ratios (ORs) of having poor or very poor perceived health (against good or very good) were calculated. In men, the ORs (and 95 percent confidence intervals) for current smokers in young (25-39) and middle age (40-59) were close to unity, but that of 1.97 (1.01, 3.85) in old age (60-74) was significantly raised. The adjusted ORs for male quitters were 1.98 (0.43, 9.14), 1.70 (0.75, 3.81) and 2.59 (1.23, 3.33) for young, middle and old age, respectively. Compared with current smokers, the adjusted ORs for quitters was 2.30 (1.07, 4.92) for those who had quit for less than 5 years, 2.02 (0.80, 5.11) for 5-9 years and 1.14 (0.47, 2.75) for 10 years or more. Among former smokers, each year of quitting was associated with 7 percent reduction in reporting poor or very poor perceived health with OR of 0.93 (0.85, 1.01). In women, the ORs were 1.95 (1.15, 3.28) for current and 1.54 (0.60, 3.94) for former smokers. In both genders combined, the overall ORs were 1.41 (1.04, 1.92) for current and 1.94 (1.27, 2.97) for former smokers. In conclusion, former smokers apparently had the worst perceived health but long-term quitting was beneficial. Overall, current smokers had worse perceived health than never smokers, but in men the excess risk was mainly observed in old age. The perceived health of smokers may have implications for the approaches used in smoking cessation.

The emergence of coronary heart disease in populations of Chinese descent.

Most countries in oriental Asia have not yet experienced the 'western' coronary heart disease (CHD) epidemic despite substantial economic development. An exception has been Singapore. We compared mortality and CHD risk factors in Singapore with two Oriental locations, Hong Kong and mainland China, which have not experienced the CHD epidemic. Mortality data from World Health Statistics Annuals age standardised for each location and were supplemented by local data. Risk factor data was obtained from population-based surveys using similar protocols in each location. Measures included diet, blood lipids, blood pressure, height and weight. CHD mortality in the year chosen for comparison, 1994, was significantly higher for Singapore Chinese males [108 (95.2-119.1)] than Chinese males in Hong Kong [44.3 (40.2-48.2)] or China [45.5 (44.2-46.8)]. Female CHD mortality was also relatively higher in Singapore Chinese. The only CHD risk factor markedly higher in Singapore Chinese was serum cholesterol; Singapore males [5.65 (5.55-5.75)], females [5.60 (5.50-5.70)], Hong Kong males [5.21 (5.11-5.31)], females [5.20 (5.10-5.29)] and China males [4.54 (4.46-4.62)], females [4.49 (4.42-4.55)]. Dietary differences in saturated fat consumption were consistent with this. Although there was little difference in total fat intake, a higher consumption of dietary saturated fat and lower consumption of polyunsaturated fat, accompanied by higher serum cholesterol, appear to explain the relatively high CHD mortality in Singapore compared with Hong Kong and mainland China. Differences in body mass index, blood pressure and smoking between locations did not explain the differences in CHD mortality.

Prevalence and correlates of alcohol use: a population-based study in Hong Kong.

OBJECTIVE: To estimate the prevalence and pattern of alcohol use and to analyse the socio-demographic and biological correlates of alcohol drinking in Hong Kong Chinese. DESIGN: A population-based cross-sectional study conducted from December 1994 to October 1996. SETTING AND PARTICIPANTS: 2900 randomly selected subjects age 25-74 years who participated in the Cardiovascular Risk Factor Prevalence Study in Hong Kong. RESULTS: Alcohol consumers comprised 55.4% (95% CI: 52.8-58.0) of men and 19.4% (95% CI: 17.4-21.4) of women. The median weekly ethanol consumed by male and female drinkers were 9.6 g and 3.6 g, respectively. Beer was the main source of alcohol; 61.5% of drinkers consumed beer as their main drink. In stepwise multiple regression among drinkers, male sex, smoking, high density lipoprotein cholesterol, primary or below education, diastolic blood pressure and separated or widowed marital status were associated positively with weekly ethanol consumption. CONCLUSION: In this representative sample of Hong Kong adults, the majority were either non-drinkers or very light drinkers, which can be used as a benchmark to measure changes in drinking pattern in the future. The putative protective effect of alcohol on heart disease could be due to the higher level of HDL in moderate drinkers.

Smoking, alcohol drinking and non-fatal coronary heart disease in Hong Kong Chinese.

PURPOSE: To examine whether smoking, alcohol drinking and other risk factors were associated with non-fatal coronary heart disease (CHD) in Hong Kong Chinese. METHODS: A case control study was carried out with 598 CHD hospital cases (431 men, 167 women) and 1100 community controls (663 men, 437 women). Standardized questionnaires were used and blood lipids were measured using standard methods. RESULTS: Stepwise logistic regression models showed adjusted odds ratios (AOR) of 3.36 [95% confidence interval (CI): 2.35 to 4.81] for smoking and 0.32 (95% CI: 0.22 to 0.45) for alcohol drinking in men, and 6.50 (95% CI: 2.61 to 16.19) and 0.15 (95% CI: 0.08 to 0.30), respectively, in women. The OR increased with decreasing levels of high-density lipoprotein cholesterol (HDL) and increasing levels of triglycerides. No patterns were observed for body mass index (BMI), total and low-density lipoprotein cholesterol (LDL). The protective effect of drinking was observed for different types of drinks and frequency of drinking, although few drank alcohol more than 3 days per week. CONCLUSIONS: Smoking was a strong risk factor and moderate alcohol drinking was a protective factor for CHD, and low HDL and high triglyceride levels were important risk factors in Hong Kong Chinese.