Residual macrovascular risk in 2013: what have we learned?

Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R3i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R3i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R3i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptorα agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R3i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk.

Risk factors associated with hypertension awareness, treatment, and control in a multi-ethnic Asian population.

OBJECTIVES: To investigate demographic and cardiovascular disease risk factors associated with awareness, treatment and control of hypertension in a multi-ethnic Asian population. METHODS: Participants from four previous cross-sectional studies were invited for a repeat examination (2004--2007). Information of demographic details and cardiovascular disease risk factors was obtained using questionnaire, physical examination and blood tests. Odds ratios and 95% confidence intervals were calculated using multiple logistic regression models. RESULTS: The final number of respondents was 5022 (response rate 49.7%). Although hypertension treatment (84.4% of those aware of hypertension) was high, awareness (51.8% of those having hypertension) and control (27.1% of hypertension on treatment) were low. Reduced awareness and treatment were associated with being younger, never married, and working adults with a higher education level. Low socioeconomic status individuals were more likely to be treated but had poorer control. A similar relationship was found for treatment and control for individuals with coexisting cardiovascular disease risk factors. The use of multiple drug classes was not associated with better control. Diuretic use for treatment of hypertension, as recommended by local and international guidelines, was not common (15.0% of all hypertension medications used). CONCLUSIONS: The awareness, treatment, and control of hypertension in Singapore can be improved. There is a need to improve awareness through education and target screening and treatment in younger, working adults with higher levels of education and higher economic status, as well as Malays. Control of hypertension could be improved among older or diabetic hypertensive individuals.

International Day for the Evaluation of Abdominal Obesity (IDEA): a study of waist circumference, cardiovascular disease, and diabetes mellitus in 168,000 primary care patients in 63 countries.

BACKGROUND: Abdominal adiposity is a growing clinical and public health problem. It is not known whether it is similarly associated with cardiovascular disease (CVD) and diabetes mellitus in different regions around the world, and thus whether measurement of waist circumference (WC) in addition to body mass index (BMI) is useful in primary care practice. METHODS AND RESULTS: Randomly chosen primary care physicians in 63 countries recruited consecutive patients aged 18 to 80 years on 2 prespecified half days. WC and BMI were measured and the presence of CVD and diabetes mellitus recorded. Of the patients who consulted the primary care physicians, 97% agreed to participate in the present study. Overall, 24% of 69,409 men and 27% of 98,750 women were obese (BMI > or = 30 kg/m2). A further 40% and 30% of men and women, respectively, were overweight (BMI 25 to 30 kg/m2). Increased WC (> 102 for men and > 88 cm for women) was recorded in 29% and 48%, CVD in 16% and 13%, and diabetes mellitus in 13% and 11% of men and women, respectively. A statistically significant graded increase existed in the frequency of CVD and diabetes mellitus with both BMI and WC, with a stronger relationship for WC than for BMI across regions for both genders. This relationship between WC, CVD, and particularly diabetes mellitus was seen even in lean patients (BMI < 25 kg/m2). CONCLUSIONS: Among men and women who consulted primary care physicians, BMI and particularly WC were both strongly linked to CVD and especially to diabetes mellitus. Strategies to address this global problem are required to prevent an epidemic of these major causes of morbidity and mortality.

Should central obesity be an optional or essential component of the metabolic syndrome? Ischemic heart disease risk in the Singapore Cardiovascular Cohort Study.

OBJECTIVE: The International Diabetes Federation (IDF) proposes that central obesity is an "essential" component of the metabolic syndrome, while the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) proposes that central obesity is an "optional" component. This study examines the effect of the metabolic syndrome with and without central obesity in an Asian population with ischemic heart disease (IHD). RESEARCH DESIGN AND METHODS: From the population-based cohort study (baseline 1992-1995), 4,334 healthy individuals were grouped by the presence or absence of the metabolic syndrome and central obesity and followed up for an average of 9.6 years by linkage with three national registries. Cox's proportional hazards model was used to obtain adjusted hazard ratios (HRs) for risk of a first IHD event. RESULTS: The prevalence of metabolic syndrome was 17.7% by IDF criteria and 26.2% by AHA/NHLBI criteria using Asian waist circumference cutoff points for central obesity. Asian Indians had higher rates than Chinese and Malays. There were 135 first IHD events. Compared with individuals without metabolic syndrome, those with central obesity/metabolic syndrome and no central obesity/metabolic syndrome were at significantly increased risk of IHD, with adjusted HRs of 2.8 (95% CI 1.8-4.2) and 2.5 (1.5-4.0), respectively. CONCLUSIONS: Having metabolic syndrome either with or without central obesity confers IHD risk. However, having central obesity as an "optional" rather than "essential" criterion identifies more individuals at risk of IHD in this Asian cohort.

Impact of sex, metabolic syndrome, and diabetes mellitus on cardiovascular events.

Although cardiovascular events occur more frequently among patients with metabolic syndrome (MS) or diabetes mellitus (DM), the impact of gender is unclear. We aimed to determine the relation of MS and DM on cardiovascular events between men and women. The National Health Survey of 1992 provided information on outcomes for 3,414 Singaporeans aged 18 to 69 years without cardiovascular diseases. Definition of MS was based on the National Cholesterol Education Program criteria. Cardiovascular events included hospital admissions for coronary heart disease, stroke, and cardiovascular mortality. The proportion of subjects with MS was 12.4%. After 10 years, the annual cardiovascular event rates (per 1,000 person-years) for men without DM were 3.0 and 15.9 among subjects without and with MS, respectively, and the respective rates for men with DM were 22.5 and 21.4. The corresponding rates for women were 0.9, 3.7, 5.3, and 21.5, respectively. Among nondiabetic subjects, cardiovascular events occurred more frequently among men than women among subjects with MS (adjusted hazard ratios [HRs] 4.71, 95% confidence interval [CI] 1.56 to 14.2) and those without MS (HR 3.35, 95% CI 1.78 to 6.31). Among patients with DM, cardiovascular events occurred more commonly among men than women without MS (HR 6.04, 95% CI 1.43 to 25.6). Rates for cardiovascular events were comparable between men and women with DM and MS (HR 0.98, 95% CI 0.48 to 1.99). In conclusion, the adverse impact of MS or DM was greater among men, and the presence of both conditions increases the risk substantially for cardiovascular events among women.

Perilipin gene variation determines higher susceptibility to insulin resistance in Asian women when consuming a high-saturated fat, low-carbohydrate diet.

OBJECTIVE: To investigate the association between genetic variation in the adipocyte protein perilipin (PLIN) and insulin resistance in an Asian population as well as to examine their modulation by macronutrient intake. RESEARCH DESIGN AND METHODS: A nationally representative sample (Chinese, Malays, and Indians) was selected in the Singapore National Health Survey following the World Health Organization-recommended model for field surveys of diabetes. A total of 1,909 men and 2,198 women (aged 18-69 years) were studied. Genetic (PLIN 11482G-->A and 14995A-->T), lifestyle, clinical, and biochemical data were obtained. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Diet was measured by a validated food frequency questionnaire in one of every two subjects. RESULTS: We did not find a significant between-genotype difference in insulin resistance measures. However, in women we found statistically significant gene-diet interactions (recessive model) between PLIN 11482G-->A/14995A-->T polymorphisms (in high linkage disequilibrium) and saturated fatty acids (SFAs; P = 0.003/0.005) and carbohydrate (P = 0.004/0.012) in determining HOMA-IR. These interactions were in opposite directions and were more significant for 11482G-->A, considered the tag polymorphism. Thus, women in the highest SFA tertile (11.8-19%) had higher HOMA-IR (48% increase; P trend = 0.006) than women in the lowest (3.1-9.4%) only if they were homozygotes for the PLIN minor allele. Conversely, HOMA-IR decreased (-24%; P trend = 0.046) as carbohydrate intake increased. These effects were stronger when SFAs and carbohydrate were combined as an SFA-to-carbohydrate ratio. Moreover, this gene-diet interaction was homogeneously found across the three ethnic groups. CONCLUSIONS: PLIN 11482G-->A/14995A-->T polymorphisms modulate the association between SFAs/carbohydrate in diet and insulin resistance in Asian women.

Ministry of Health Clinical Practice Guidelines: Lipids.

The Ministry of Health (MOH) has updated the Clinical Practice Guidelines on Lipids to provide doctors and patients in Singapore with evidence-based treatment for lipids. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH Clinical Practice Guidelines on Lipids, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html.

Modification of the NCEP ATP III definitions of the metabolic syndrome for use in Asians identifies individuals at risk of ischemic heart disease.

The association between the metabolic syndrome (MS) to ischemic heart disease (IHD) has not been established prospectively in Asian populations. We carried out registry linkage, using unique national identity numbers, to identify incident IHD events in subjects without diabetes mellitus or IHD from two cross-sectional studies of Chinese, Malays and Asian Indians living in Singapore. The risk of IHD associated with the MS (NCEP ATP III criteria) was determined by Cox-proportional hazards regression before and after adjustment for age, sex, ethnic group and current cigarette smoking. We also assessed the utility of modified Asian criteria (reducing the waist circumference (WC) used to define central obesity to 90 cm in men and 80 cm in women) on the risk of IHD associated with the MS. This study provided 38,157.4 person-years in 4042 subjects who experienced 93 incident IHD events. MS (as defined by the NCEP ATP III criteria) was associated with increased risk of IHD (HR3.09; 95% CI 1.96-4.88). Those who satisfied only the modified Asian criteria, but not the NCEP ATP III criteria, were also at increased risk of IHD (HR 2.13; 95% CI 0.99-4.58). It would be appropriate to lower the cut-off for WC used for the diagnosis of the MS in such populations.

Usefulness of the Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) questionnaire in patients with diabetes in a multi-ethnic Asian country.

INTRODUCTION: Asia will be at the forefront of the current epidemic of diabetes mellitus. Quality of life (QOL) is an important outcome measure in the assessment of diabetes care. However, few QOL instruments are culturally suitable for use in Asian countries. The Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) questionnaire is a third-generation individualised QOL instrument. Individualised instruments such as the ADDQoL have the potential to be useful and less costly alternatives to computerised adaptive testing (CAT), which may not be practical in developing countries. OBJECTIVE: To evaluate and validate the ADDQoL questionnaire in English-speaking patients with diabetes in Singapore, a multi-ethnic Asian country. METHODS: The ADDQoL and EQ-5D were administered to English-speaking respondents with type 1 or 2 diabetes (aged > or =18 years) recruited from a tertiary acute-care referral hospital by convenience sampling. The usefulness of the key design features of the ADDQoL were assessed by measuring the number of zero-importance responses, the change in item ranking with and without weighting for importance, and the frequency of utilisation of the 'not applicable' (NA) options. The acceptability, factor structure and internal consistency (Cronbach's alpha) of the ADDQoL were also assessed. Data were subjected to unforced factor analysis with oblimin rotation and then the condition was set to force a one-factor solution. The validity of the ADDQoL was tested with the following hypotheses: those with moderate or severe problems on the EQ-5D would have worse ADDQoL average weighted impact (AWI) scores than those with a perfect health rating on the EQ-5D; those with better Present QOL scores on the ADDQoL would have better EQ-5D utility and visual analogue scale (VAS) scores; on the ADDQoL, AWI scores would correlate better with diabetes-dependent QOL than with Present QOL scores; and female respondents, those who required insulin or had longer duration of known diabetes would have worse ADDQoL AWI scores (known-group validity). RESULTS: We analysed data from 152 respondents (49% Chinese, 34% Indian; 45% female; mean age 52 years, range 18-80; mean duration of known diabetes 10 years, range 0-62). There were few missing data. Weighted scoring and NA options were shown to be necessary, thus supporting the usefulness of individualised health-related QOL measures. Factor structure of the ADDQoL was supported and internal consistency was high (alpha = 0.94). All hypotheses were fulfilled except for one that was partially fulfilled; respondents with longer duration of known diabetes did not report worse ADDQoL AWI scores. CONCLUSIONS: The ADDQoL is culturally appropriate, valid, reliable and well accepted among Singaporean patients with diabetes. Individualised measures such as the ADDQoL allow one to obtain precise score estimates and may offer developing countries a useful alternative to CAT.

Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population.

Perilipin is a lipid droplet surface protein present in adipocytes and steroidogenic cells. We examined five common single nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus (PLIN 6209C>T, 10171A>T, 11482G>A, 13041A>G, and 14995A>T) to investigate their association with obesity risk. The study population included 4,131 subjects of three ethnic groups (Chinese, Malay, and Indian) from Singapore. The prevalence of obesity in Malays and Indians was much higher than in Chinese. Moreover, in these groups the prevalence of obesity was three times higher in women than in men. Crude analysis indicated that haplotype 11212 (CAAAT) is shared by Malays and Indians and is significantly associated with increased obesity risk as compared to the most common haplotype 21111 (TAGAA): OR 1.65 (95% CI 1.11-2.46) in Malays and 1.94 (95% CI 1.06-3.53) in Indians. No associations between PLIN haplotypes and obesity risk were found in Chinese. To simplify the haplotype analyses we used a subgroup of three SNPs (11482G>A, 13041A>G, and 14995A>T) in positive linkage disequilibrium. These analyses revealed similar associations, showing that haplotypes XX212 (XXAAT) and XX222 (XXAGT) are associated with increased obesity risk in Malays OR 2.04 (95% CI 1.28-3.25) and 2.05 (95% CI 1.35-3.12) respectively, and that haplotype XXX212 (XXAAT) is significantly associated with increased obesity risk in Indians OR 2.16 (95% CI 1.10-4.26) after adjusting for covariates including age, sex, smoking, alcohol consumption, exercise, and diabetes status. Moreover, individual SNP analyses demonstrated that the PLIN 14995A>T SNP is the most informative single genetic marker for the observed haplotype association, being significantly associated with increased obesity risk in both Malays OR 2.28 (95% CI 1.45-3.57) and Indians OR 2.04 (95% CI 1.08-3.64). These results support the role of the PLIN locus as an ethnically dependent modulator of obesity risk in humans.

The metabolic syndrome in Chinese, Malays and Asian Indians. Factor analysis of data from the 1998 Singapore National Health Survey.

We used factor analysis to define and compare the manner in which the various features of the metabolic syndrome are linked or clustered in Chinese, Malays and Asian Indians. One thousand nine hundred and fifty seven men (1324 Chinese, 391 Malays and 261 Asian Indians) and 2308 women (1622 Chinese, 391 Malays and 296 Asian Indians) were examined. Anthropometry, blood pressure, serum glucose, lipid concentrations, and serum insulin were measured for all subjects. These data were then subjected to factor analysis which reduced the variables examined to three factors in all ethnic groups and both genders. The first (dyslipidemia) factor was positively loaded for obesity, insulin resistance (IR), fasting triglyceride and negatively loaded for HDL-cholesterol. The second (hyperglycemia) factor was positively loaded for IR and blood glucose. The third (hypertension) factor was positively loaded for obesity and blood pressure. IR was positively loaded in the hypertension factor in Malay women but not in others. Rather than a single entity causally associated with insulin resistance (IR), our findings support a concept in which the metabolic syndrome represents several distinct entities (dyslipidemia, hypertension and hyperglycemia). It appears that Malay females may be more prone to develop hypertension in association with IR.

Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians?

OBJECTIVE: Limited information is available about the metabolic syndrome in Asians. Furthermore, the definition of central obesity using waist circumference may not be appropriate for Asians. The objectives of this study were to determine the optimal waist circumference for diagnosing central obesity in Asians and to estimate the prevalence of the metabolic syndrome in an Asian population. RESEARCH DESIGN AND METHODS: We used data from the 1998 Singapore National Health Survey, a cross-sectional survey involving 4,723 men and women of Chinese, Malay, and Asian-Indian ethnicity aged 18-69 years. Receiver operating characteristic analysis suggested that waist circumference >80 cm in women and >90 cm in men was a more appropriate definition of central obesity in this population. The prevalence of the metabolic syndrome was then determined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with and without the modified waist circumference criteria. RESULTS: In Asians, decreasing waist circumference increased the crude prevalence of the metabolic syndrome from 12.2 to 17.9%. Using the modified Asian criteria, the prevalence of the metabolic syndrome increased from 2.9% in those aged 18-30 years to 31.0% in those aged 60-69 years. It was more common in men (prevalence 20.9% in men versus 15.5% in women; P < 0.001) and Asian Indians (prevalence 28.8% in Asian-Indians, 24.2% in Malays, and 14.8% in Chinese; P < 0.001). CONCLUSIONS: NCEP ATP III criteria, applied to an Asian population, will underestimate the population at risk. With a lower waist circumference cutoff, the prevalence of the metabolic syndrome is comparable to that in Western populations. Ethnic differences are likely to exist between populations across Asia.

Lowering the criterion for impaired fasting glucose: impact on disease prevalence and associated risk of diabetes and ischemic heart disease.

OBJECTIVE: To determine the effect of lowering the fasting plasma glucose (FPG) criterion for impaired fasting glucose (IFG) on the prevalence of IFG, the risks of diabetes, and cardiovascular disease (CVD) associated with IFG. RESEARCH DESIGN AND METHODS: Three studies were used: 1). the 1998 National Health Survey (NHS98), a randomly selected cross-sectional sample of 4723 subjects; 2). the Singapore Impaired Glucose Tolerance (IGT) Follow-up Study, a cohort study comprising 295 IGT and 292 normal glucose tolerance subjects (frequency matched for age, sex, and ethnic group) followed up from 1992 to 2000; and 3). the Singapore CVD Cohort Study, comprising 5920 subjects from three cross-sectional studies in whom the first ischemic heart disease (IHD) event was identified through linkage to registry databases. Risk of diabetes (Singapore IGT Follow-up study) was estimated using logistic regression adjusted for age, sex, and ethnicity. Risk of IHD (Singapore CVD cohort) was estimated using stratified (by study, from which data were derived) Cox's proportional hazards models adjusted for age, sex, and ethnicity. RESULTS: Lowering the criterion for diagnosing IFG to 5.6 mmol/l increased the prevalence of IFG from 9.5 to 32.3% in the NHS98. The lower cutoff identified more subjects at risk of diabetes and IHD, but the relative risk was lower than that for IGT. CONCLUSIONS: Greater efforts to identify those with IGT, or a group at similar risk of diabetes and CVD, may be a more efficient public health measure than lowering the FPG criterion for diagnosing IFG.

Usefulness of measuring both body mass index and waist circumference for the estimation of visceral adiposity and related cardiometabolic risk profile (from the INSPIRE ME IAA study).

Despite its well-documented relation with visceral adiposity (VAT) and cardiometabolic risk (CMR), whether waist circumference (WC) should be measured in addition to body mass index (BMI) remains debated. This study tested the relevance of adding WC to BMI for the estimation of VAT and CMR. In the International Study of Prediction of Intra-abdominal Adiposity and Its Relationship with Cardiometabolic Risk/Intra-abdominal Adiposity, 297 physicians recruited 4,504 patients (29 countries). Both BMI and WC were measured, whereas VAT and liver fat were assessed by computed tomography. A composite CMR score was calculated. From the 4,109 patients included in the present analyses (20 ≤ BMI < 40 kg/m(2), 47% women), about 30% displayed discordant values for WC and BMI quintiles, despite a strong correlation between the 2 anthropometric variables (r = 0.87 and r = 0.84 for men and women, respectively, p <0.001). Within each single BMI unit, VAT and WC showed substantial variability between subjects (mean difference between 90th and 10th percentiles: 175 cm(2)/16 cm and 137 cm(2)/18 cm for VAT/WC in men and women, respectively). Within each BMI category, increasing gender-specific WC tertiles were associated with significantly higher VAT, liver fat, and with a more adverse CMR profile. In conclusion, this large international cardiometabolic study highlights the frequent discordance between BMI and WC, driven by the substantial variability in VAT for a given BMI. Within each BMI category, WC was cross-sectionally associated with VAT, liver fat, and CMR factors. Thus, WC allows a further refinement of the CMR related to any given BMI.

Hepatic expression of PPARalpha, a molecular target of fibrates, is regulated during inflammation in a gender-specific manner.

Dyslipidemia, inflammation and gender are major risk factors in cardiovascular disease. Here we show that hepatic expression of Peroxisome proliferator-activated receptor alpha (PPARalpha), a nuclear receptor that regulates lipid metabolism and inflammation, is regulated in a gender-specific manner during lipopolysaccharide (LPS)-induced systemic inflammation. Immediately following LPS-induced systemic inflammation, hepatic PPARalpha mRNA level decreased dramatically in mice. It was restored to baseline within 24 h in females but remained below baseline for >72 h in male mice. In gonadectomized mice of both sexes, PPARalpha mRNA level was restored to baseline within 48 h after the initial decrease.

Risk factors for coronary heart disease in the Japanese--comparison of the background of patients with acute coronary syndrome in the ASPAC study with data obtained from the general population. Asia-Pacific Collaboration on CHD Risk Factor Intervention study.

The relative importance of metabolic risk factors for coronary heart disease (CHD) in the Japanese is assessed by comparing their prevalence in patients with acute coronary syndrome (ACS) enrolled in the Asia-Pacific Collaboration on CHD Risk Factor Intervention (ASPAC) study to that obtained by a serum lipid survey carried out in 1990 and also by comparing them to the ASPAC data from other countries and regions in this area. Hypertension was the most prevalent risk factor among Japanese patients with ACS as in the other countries and regions. The prevalence of obesity with a body mass index (BMI) of 30 or more was several times higher than that in the general population, although the rate was still much lower than in New Zealand and Singapore. In addition to hypercholesterolemia, hypertriglyceridemia and diabetes mellitus were frequently found in Japanese patients with ACS. When the prevalence of metabolic risk factors was compared between people with and without hypertension in the general population, the most remarkable difference was seen in BMI, followed by triglyceride and total cholesterol. These results indicate that hypertriglyceridemia and diabetes mellitus may be more important CHD risk factors in the Japanese population than LDL-cholesterol.

Lipid management in Diabetes Mellitus: A Singapore Perspective

Patients with Diabetes Mellitus (DM) have increased risk of atherosclerosis and up to half die during the first myocardial infarction. Primary prevention of cardiovascular disease (CVD) should be a major goal in the management of DM patients. DM patients with the highest risk (established CVD or chronic kidney disease) should have aggressive lipid-lowering therapy. Statin therapy should be the first line of therapy for all DM patients with elevated LDL-C. Ezetimibe can be added if LDL-C target is not reached at maximally tolerated statin dose. Fibrates can be used in DM patients with TG of >4.5 mmol/l (400 mg/dl). The adverse effects from lipid-lowering therapy are low while the benefits of intervention are well proven and significant.

The GIANT study, a cluster-randomised controlled trial of efficacy of education of doctors about type 2 diabetes mellitus management guidelines in primary care practice.

OBJECTIVES: Primary aim: does general practitioner (GP) education on type 2 diabetes treatment improve HbA1c? Secondary aim: cardiovascular risk factors, hypoglycaemia, treatment intensification, health service utilisation, treatment barriers. METHODS: 99 Asia-Pacific GPs were cluster-randomised to be educated on regional diabetes management guidelines (intervention) or continue standard care (control). The intervention employed meetings, reminders, medical record summary sheets and patient result cards. Each GP recruited four type 2 diabetic patients, assessed at baseline, 6 and 12 months. The primary outcome was mean change in HbA1c from 0 to 6 months in patients with baseline HbA1c≥6.5%. RESULTS: 361 patients (93%) completed 6 month follow-up. The primary HbA1c outcome was -0.11% (95% CI -0.27, 0.05) with intervention and -0.22% (95% CI -0.39, -0.05) in the control group (p=0.340). The groups did not differ in control of other glycaemic indices, blood pressure or lipids after 6 or 12 months. In those with HbA1c≥9.0%, approximately 50% received intensified treatment by 6 months, and 30% in the final 6 months. GPs identified treatment costs and patient reluctance to use insulin as management barriers. CONCLUSIONS/INTERPRETATION: A structured GP education programme did not improve HbA1c in patients with type 2 diabetes.

Effects of rosuvastatin on low-density lipoprotein cholesterol and plasma lipids in Asian patients with hypercholesterolemia.

AIMS: Rosuvastatin is more efficacious than other statins in lowering low-density lipoprotein cholesterol (LDL-C). Studies showing higher blood levels in Asians have resulted in concerns regarding increased adverse drug reactions. This study aimed to evaluate the efficacy and safety of rosuvastatin in hypercholesterolemic Asian patients. METHODS: This retrospective observational study was conducted on statin-naive patients and statin-switch patients. Patients were treated with rosuvastatin for > or =8 weeks. Primary outcomes were changes in LDL-C levels and proportions of patients achieving their goals (primary prevention, LDL-C < or =130 mg/dL; secondary prevention, LDL-C< or =100 mg/dL). RESULTS: Of 1007 hypercholesterolemic patients, 483 were statin-naive (LDL-C 161+/-40.8 mg/dL) and 524 were statin-switch patients (LDL-C 132.7+/-36.9 mg/dL). In statin-naive patients, rosuvastatin significantly reduced LDL-C, total cholesterol, and triglycerides by 39.9%, 28.8%, and 9.2%, respectively (p<0.001). Eighty-one percent of these patients achieved LDL-C goals. In the statin-switch cohort, LDL-C, total cholesterol, and triglycerides levels were significantly reduced by 24.5%, 16.6%, and 3.8%, respectively (p<0.001). Achievement of target LDL-C levels increased from 29% to 72.9%. There was no significant adverse drug reaction. CONCLUSION: Rosuvastatin was well tolerated and effective in lowering LDL-C in hypercholesterolemic Asian patients. Patients whose LDL-C levels were suboptimal on other statins improved their levels and more achieved LDL-C goals after switching to rosuvastatin.

Metabolic syndrome: recent prevalence in East and Southeast Asian populations.

BACKGROUND: The prevalence of the metabolic syndrome among a number of Asian populations as defined by several current criteria has been increasing rapidly and appears to resemble that among Western populations. METHODS: We review 25 surveys of the metabolic syndrome in Asian populations (PR China, Hong Kong, Taiwan, Japan, Philippines, Singapore) that report adequate information published during the last 5 years. RESULTS: Using Asian-adapted definitions of obesity (BMI > or = 25 kg/m(2)) and increased waist circumference (for male > or = 90 cm; for female > or =80 cm) prevalence appears to be between 10 to 30%. Those with the syndrome are more likely to have a history of diabetes and cardiovascular disease. The risk of developing Type 2 diabetes is 10 times higher among middle-aged Japanese men with the metabolic syndrome compared to healthy subjects. In Chinese and Japanese populations, people who have the metabolic syndrome are 3 to 10 times more likely to develop cardiovascular disease. Variance in prevalence estimates of the metabolic syndrome even within the same country result from differences in sampling and possibly from definitions. CONCLUSIONS: The outstanding conclusion from recent surveys across the Asian-Pacific region is that of a consistent increase in the prevalence of the metabolic derangements associated with abdominal adiposity that lead to high risk of morbidity and mortality.