Effect of alirocumab on cardiovascular outcomes after acute coronary syndromes according to age: an ODYSSEY OUTCOMES trial analysis.

AIMS: Lowering low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular risk irrespective of age, but the evidence is less strong for older patients. METHODS AND RESULTS: This prespecified analysis from ODYSSEY OUTCOMES compared the effect of alirocumab vs. placebo in 18 924 patients with recent acute coronary syndrome (ACS) according to age. We examined the effect of assigned treatment on occurrence of the primary study outcome, a composite of coronary heart disease death, myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization [major adverse cardiovascular event (MACE)] and all-cause death. Relative risk reductions were consistent for patients ≥65 vs. <65 years for MACE [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.68-0.91 vs. 0.89, 0.80-1.00; Pinteraction = 0.19] and all-cause death [HR 0.77, 0.62-0.95 vs. 0.94, 0.77-1.15; Pinteraction = 0.46], and consistent for MACE when dichotomizing at age 75 years (HR 0.85, 0.64-1.13 in ≥75 vs. 0.85, 0.78-0.93 in <75, Pinteraction = 0.19). When considering age as a continuous variable in regression models, advancing age increased risk of MACE, as well as the absolute reduction in MACE with alirocumab, with numbers-needed-to-treat for MACE at 3 years of 43 (25-186) at age 45 years, 26 (15-97) at age 75 years, and 12 (6-81) for those at age 85 years. Although adverse events were more frequent in older patients, there were no differences between alirocumab and placebo. CONCLUSION: In patients with recent ACS, alirocumab improves outcomes irrespective of age. Increasing absolute benefit but not harm with advancing age suggests that LDL-C lowering is an important preventive intervention for older patients after ACS.

Gaps in beliefs and practice in dyslipidaemia management in Japan, Germany, Colombia and the Philippines: insights from a web-based physician survey.

BACKGROUND: Implementing evidence-based management of dyslipidaemia is a challenge worldwide. OBJECTIVES: To understand physician beliefs and behaviour and identify uncertainties in dyslipidaemia management across four world regions. METHODS: Web-based survey of 1758 physicians in Japan, Germany, Colombia and the Philippines who were selected randomly from existing databases. Key inclusion criteria were 1) for cardiologists and diabetes/endocrinology specialists: ≥50 dyslipidaemia patients examined in the last month; 2) for specialists in neurology/neurosurgery/stroke medicine: ≥50 dyslipidaemia patients and ≥ 20 patients with a history of ischaemic stroke examined in the last month; and 3) for specialists in nephrology and general medicine: based at centres with ≥20 beds and ≥ 50 dyslipidaemia patients examined in the last month. The self-report survey covered dyslipidaemia management, target low-density lipoprotein cholesterol (LDL-C) levels in different patient groups, and statin safety. All physicians gave voluntary consent and all data were anonymised. Analysis was solely descriptive. RESULTS: The survey highlighted key areas of uncertainty in dyslipidaemia management in the four countries. These related to LDL-C targets in different patient groups, the safety of low LDL-C levels, the safety of statins, especially for effects on cognitive, renal and hepatic function and for haemorrhagic stroke risk, and lipid management strategies in patients with chronic kidney disease, including those with concomitant hypertriglyceridaemia. CONCLUSIONS: This survey of physicians in Japan, Germany, Colombia and the Philippines has identified key gaps in knowledge about dyslipidaemia management. These relate to the safety of low LDL-C levels, the safety of statins, and lipid management of chronic kidney disease. The findings from this survey highlight the need for further education to improve the implementation of guideline recommendations for dyslipidaemia management.

Darapladib for preventing ischemic events in stable coronary heart disease.

BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. METHODS: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). RESULTS: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). CONCLUSIONS: In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

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.

Community Health Workers' Concept and Understanding of Diabetes: A Qualitative Study.

Objectives: Community health workers (CHWs) fill in the insufficiency of health professionals in low-income countries. The CHWs' roles include health education of their constituents whose health they likewise take care. This study aimed to describe the concept and understanding of diabetes among CHWs in the Philippines. Methods: Fifty female CHWs currently working in rural and urban areas participated in six focus group discussions with guidance from Kleinman's eight questions. With the written informed consent of the participants, discussions were recorded and transcribed by the Research Assistant. A multi-disciplinary team manually analyzed the data. Disagreements were discussed among them and the physicians provided clinical analyses and explanations on the results. Quotations of an important point of view were also presented. Pseudonyms were utilized to uphold anonymity. Results: CHWs were aged 32 to 72 years; older participants reside in rural areas. Majority were married, housekeepers, and high school graduates. Some CHWs and their family were suffering from diabetes or dyabetis, the disease of the rich according to them. Its causes were food and lifestyle, and believed to be hereditary. Complications lead to death. Amputation was feared the most. Diabetes is incurable. Persons with diabetes should take maintenance medicines, and seek physicians' and family's help. Together with the patient, the family must decide on its management. Balanced diet, healthy lifestyle, maintenance medicines, food supplements, and herbal plants were perceived treatments. The internist should lower blood sugar level as well as prolong life span. Proper diet and regular check-up prevent diabetes. Conclusions: CHWs' concept and understanding of diabetes reflect some of the biomedical causes, effects, treatment, and prevention of diabetes as well as its social determinants. The efficacy and safety of herbal plants in the treatment of diabetes, however, should be further studied. Training on diabetes care should be provided to address their fears of amputation, insulin injection, and complications.

Prevalence of atherosclerosis-related risk factors and diseases in the Philippines.

BACKGROUND: We conducted a survey in 2008 to measure the prevalence of lifestyle-related diseases and risk factors in Philippine adults. METHODS: Stratified multistage sampling was used to cover the entire Philippine population of adults aged 20 years or older. Using health questionnaires, anthropometric measurements, and blood examinations, the prevalences of atherosclerosis-related risk factors and diseases were determined. Survey results were compared with those obtained in 2003. RESULTS: Out of 7700 eligible subjects, 64% to 93.7% responded to different survey items. Age-adjusted hypertension prevalence was 24.6% at a single visit and 20.6% when corrected for true prevalence. The prevalence of diabetes was 3.9% on the basis of fasting blood glucose (FBG), 5.2% by FBG and history, and 6.0% when 2-hour post-load plasma glucose level was determined. The prevalence of dyslipidemia was 72.0% and the prevalence of smoking was 31%. The prevalence of obesity was 4.9% by body mass index (BMI), and 10.2% and 65.6% by waist-hip ratio (WHR) in men and women, respectively. The prevalences of coronary, cerebrovascular, and peripheral arterial diseases were 1.1%, 0.9%, and 1.0%, respectively. CONCLUSIONS: The prevalences of risk factors for atherosclerosis were higher in 2008 than in 2003, although the increase in diabetes was not significant and smoking decreased. These findings indicate a need for active collaborative intervention by all government agencies and medical societies in the Philippines.

The rs1458038 variant near FGF5 is associated with poor response to calcium channel blockers among Filipinos.

ABSTRACT: Genetic variation is known to affect response to calcium channel blockers (CCBs) among different populations. This study aimed to determine the genetic variations associated with poor response to this class of antihypertensive drugs among Filipinos.One hundred eighty one hypertensive participants on CCBs therapy were included in an unmatched case-control study. Genomic deoxyribonucleic acid were extracted and genotyped for selected genetic variants. Regression analysis was used to determine the association of genetic and clinical variables with poor response to medication.The variant rs1458038 near fibroblast growth factor 5 gene showed significant association with poor blood pressure-lowering response based on additive effect (CT genotype: adjusted OR 3.41, P = .001; TT genotype: adjusted OR 6.72, P < .001).These findings suggest that blood pressure response to calcium channels blockers among Filipinos with hypertension is associated with gene variant rs1458038 near fibroblast growth factor 5 gene. Further studies are recommended to validate such relationship of the variant to the CCB response.

The Klotho Variant rs36217263 Is Associated With Poor Response to Cardioselective Beta-Blocker Therapy Among Filipinos.

A common drug used for hypertension among Filipinos is beta-blockers. Variable responses to beta-blockers are observed, and genetic predisposition is suggested. This study investigated the association of genetic variants with poor response to beta-blockers among Filipinos. A total of 76 Filipino adult hypertensive participants on beta-blockers were enrolled in an unmatched case-control study. Genotyping was done using DNA from blood samples. Candidate variants were correlated with clinical data using χ2 and logistic regression analysis. The deletion of at least one copy of allele A of rs36217263 near Klotho showed statistically significant association with poor response to beta-blockers (dominant; odds ratio (OR) = 3.89; P = 0.017), adjusted for diabetes and dyslipidemia. This association is observed among participants using cardioselective beta-blockers (crude OR = 5.60; P = 0.008) but not carvedilol (crude OR = 2.56; P = 0.67). The genetic variant rs36217263 is associated with poor response to cardioselective beta-blockers, which may become a potential marker to aid in the management of hypertension.

Prevalence of Metabolic Syndrome and Cardiovascular Risk Factors among Community Health Workers in Selected Villages in the Philippines.

OBJECTIVE: This study aimed to estimate the prevalence of cardiovascular risk factors and metabolic syndrome among community health workers (CHWs) in selected villages in the Philippines. It also determined the association of urbanization and socio-demographic characteristics with hypertension, diabetes mellitus and metabolic syndrome among CHWs. METHODOLOGY: A cross-sectional study was conducted among CHWs who were actively rendering service from selected communities at the time of the study. Standardized interviews were conducted and clinical measurements were collected. RESULTS: Of the total of 457 CHWs who participated, 96% were females with a median age of 50 years. The prevalence of hypertension in this population was 32.4%. Hypertension was found to be associated with older age [adjusted odds ratio (aOR) 5.3, 95% CI: 3.2 to 8.8, p<0.001], obesity (aOR 2.4, 95% CI: 1.4 to 4.0, p=0.002) and alcohol consumption (aOR 1.7, 95% CI: 1.0 to 3.0, p<0.040). The prevalence of diabetes mellitus (DM) was 13.6%. It was found to be more prevalent among CHWs who were at least 50 years old (aOR 2.7, 95% CI: 1.4 to 5.1, p=0.002), and those who spent at least 5 hours a day in sedentary activities (aOR 3.8, 95% CI: 1.1 to 12.7, p<0.033). Borderline to high total cholesterol, low density lipoprotein cholesterol (LDL-c) and triglycerides (TG) were seen in 41%, 37% and 20%, respectively. Sixty percent had low high density lipoprotein cholesterol (LDL-c). The overall prevalence of metabolic syndrome was 52.3%. CONCLUSION: Metabolic syndrome is prevalent among CHW participants, with obesity, hypertension and low LDL-c as the most common components present. The prevalence of cardiovascular risk factors in this population was not found to be significantly different between rural and urban areas after adjusting for other factors.

Metabolic syndrome in the Philippine general population: prevalence and risk for atherosclerotic cardiovascular disease and diabetes mellitus.

The objectives of this study were to determine the prevalence of metabolic syndrome (MS) and its component risk factors among Filipinos using three sets of criteria and to evaluate the association between MS and atherosclerotic cardiovascular disease and diabetes mellitus. The study utilised a multi-staged cluster sampling design. The prevalence of MS was found to be 11.9% by National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) criteria, 14.5% by International Diabetes Federation (IDF) criteria and 18.6% by NCEP/ATP III criteria modified by the American Heart Association/National Heart, Lung and Blood Institute (NCEP/ATP III-AHA/NHLBI) criteria. Low levels of high-density lipoprotein cholesterol (HDL-C) occurred in 60.2% of men and 80.9% of women. Abdominal obesity was noted in 17.7% of men and 35.1% of women. Blood pressure (BP) > or = 130/85 mmHg was seen in 33.3%, hypertriglyceridaemia in 20.6% and fasting blood sugar > or = 100 mg/dL (5.55 mmol/L) in 7.1%. Age-adjusted odds ratios showed that MS, by all three definitions, predisposed an individual to diabetes mellitus (DM) and stroke while MS by the IDF definition predisposed an individual to myocardial infarction (MI). Individuals with MS did not have a significant predisposition to angina and peripheral artery disease (PAD). Thus, the metabolic syndrome is common in Filipinos, with low HDL-C as the most prevalent component. The metabolic syndrome predisposes to diabetes mellitus and stroke, with a tendency to MI using the IDF criteria.

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patient.

Despite current standards of care aimed at achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure and glycaemia, dyslipidaemic patients remain at high residual risk of vascular events. Atherogenic dyslipidaemia, specifically elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease, type 2 diabetes, obesity or metabolic syndrome and is associated with macrovascular and microvascular residual risk. The Residual Risk Reduction Initiative (R3I) was established to address this important issue. This position paper aims to highlight evidence that atherogenic dyslipidaemia contributes to residual macrovascular risk and microvascular complications despite current standards of care for dyslipidaemia and diabetes, and to recommend therapeutic intervention for reducing this, supported by evidence and expert consensus. Lifestyle modification is an important first step. Additionally, pharmacotherapy is often required. Adding niacin, a fibrate or omega-3 fatty acids to statin therapy improves achievement of all lipid risk factors. Outcomes studies are evaluating whether these strategies translate to greater clinical benefit than statin therapy alone. In conclusion, the R3I highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual vascular risk among dyslipidaemic patients who are treated in accordance with current standards of care.

Cardiac events occurred commonly among apparently healthy Filipinos with the Brugada ECG pattern in the LIFECARE cohort.

BACKGROUND: Brugada syndrome is the mechanism for sudden unexplained death. The Brugada ECG pattern is found in 2% of Filipinos. There is a knowledge gap on the clinical outcome of these individuals. The clinical profile and 5-year cardiac event rate of individuals with the Brugada ECG pattern were determined in this cohort. METHODS: This is a sub-study of LIFECARE (Life Course Study in Cardiovascular Disease Epidemiology), a community based cohort enrolling healthy individuals 20 to 50 years old conducted in 2009-2010. ECGs of all enrollees were screened independently by three cardiologists. The prevalence of the coved Brugada ECG pattern was ascertained, and the 5-year cardiac event rate was determined among those individuals with this pattern. The participants were contacted to determine the occurrence of cardiac events, which included syncope, presyncope, seizures, cardiac arrest and unexplained vehicular accidents. RESULTS: A total of 3072 ECGs were reviewed, and 14 subjects (0.4%) with the coved Brugada ECG pattern were identified. Four had a cardiac event on follow-up at 5 years, but all remained alive. Most of these 14 coved Brugada individuals were healthy and asymptomatic at baseline. CONCLUSION: Cardiac events occurred commonly among initially asymptomatic Filipinos with the coved Brugada ECG pattern. Such patients need to be followed up closely.

Human cholestryl ester transfer protein (TaqIB) polymorphism among Filipinos with cardiovascular risk factors.

BACKGROUND: HDL-C has emerged as an important independent predictor of cardiovascular disease. The FNRI-HDL and NNHes Study Group in the Philippines reported that there was a high prevalence of low HDL among Filipinos. Most cases of low HDL-C are associated with secondary causes like Metabolic Syndrome. A primary cause of reduced HDL-C such as increase Cholesteryl Ester Transfer Protein activity has been identified. OBJECTIVES: 1. To determine the phenotype and frequency of Cholesteryl Ester Transfer Protein (TaqIB) polymorphism among Filipinos with cardiovascular risk factors. 2. To determine the association of TaqIB polymorphism with HDL-C levels among Filipinos with cardiovascular risk factors. DESIGN: Cross-sectional Study. SETTING: University of the Philippines-Philippine General Hospital. STATISTICAL ANALYSIS: Descriptive statistics, Chi square test and Fisher's correlation test using Stata version 6. METHODS: Fifty patients were included in this pilot study and were examined with respect to genotype, lipid profiles, blood sugar and other cardiovascular risk factors. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP) and Agarose Gel Electrophoresis techniques were used to determine the CETP TaqIB Polymorphism. RESULTS: Out of 50 patients, 66% were females and 34% were males with a mean age of 55 y/o and a BMI of 27 kg/m(2). The following risk factors were identified: hypertension (92%), dyslipidemia (88%), obesity (68%), smoking (50%), diabetes mellitus type 2 (18%) and family history of premature CAD (14%). The genotype frequencies of B1B1; B1B2; B2B2 were 40%; 50% 10% respectively. The B1B1 homozygote was associated with lower HDL-C levels (45.35 +/- 8.82 mg/dL) compared to B1B2 (48.96 +/- 10.10 mg/dL) and B2B2 (48.99 +/- 10.13 mg/dL)). CONCLUSIONS: Cholesteryl Ester Transfer Protein (TaqIB) Polymorphisms exist among Filipinos with cardiovascular risk factors. The frequency of TaqIB polymorphism among Filipinos with cardiovascular risk factors were B1B1 (40%), B1B2 (50%) and B2B2 (10%). B1B1 polymorphism is more common than B2B2 and associated with low HDL-C.

World Heart Federation Cholesterol Roadmap.

BACKGROUND: The World Heart Federation has undertaken an initiative to develop a series of Roadmaps. OBJECTIVES: The aim of these is to promote development of national policies and health systems approaches and identify potential roadblocks on the road to effective prevention, detection and management of cardiovascular disease (CVD) in low-and middle-income countries (LMIC), and strategies for overcoming these. This Roadmap focuses on elevated blood cholesterol, a leading risk factor for myocardial infarction, stroke, and peripheral arterial disease. METHODS: Through a review of published guidelines and research papers, and consultation with a committee composed of experts in clinical management of cholesterol and health systems research in LMIC, this Roadmap identifies (1) key interventions for primordial, primary and secondary prevention of CVD through detection, treatment, and management of elevated cholesterol and familial hypercholesterolemia (FH); (2) gaps in implementation of these interventions (knowledge-practice gaps); (3) health system roadblocks to treatment of elevated cholesterol in LMIC; and (4) potential strategies for overcoming these. RESULTS: Despite strong evidence of the importance of cholesterol levels in primary or secondary prevention of CVD, and the effectiveness of statin therapy for cholesterol lowering and reduction of CVD risk, gaps exist in the detection, treatment, and management of high cholesterol globally. Some potential roadblocks include poor access to laboratory facilities or trained professionals for cholesterol management, low awareness of FH among the general population and health professionals, unaffordability of statins for patient households, and low awareness of the importance of persistent adherence to lipid-lowering medication. Potential solutions include point-of-care testing, provision of free or subsidized lipid-lowering medication, and treatment adherence support using text message reminders. CONCLUSIONS: Known effective strategies for detection, treatment, and management of elevated cholesterol and FH exist, but there are barriers to their implementation in many low-resource settings. Priorities for health system intervention should be identified at the national level, and the feasibility and effectiveness of proposed solutions should be assessed in specific contexts. Many solutions proposed in this Roadmap may apply to other cardiovascular conditions and present opportunities for integration of CVD care in LMIC.

Low density lipoprotein--receptor (LDL-R) gene mutations among Filipinos with familial hypercholesterolemia.

BACKGROUND: Familial Hypercholesterolemia (FH) is an autosomal dominant disease resulting from mutations of the LDL (LDLR) receptor gene leading to a diminished catabolism and elevated level of LDL cholesterol (LDL-C). It is associated with an increased risk for cardiovascular disease (CVD). The MEDPED (Make Early Diagnosis-Prevent Early Death) program, an initiative cited by the WHO Human Genetics Programme in their report on FH, initiated international collaboration to identify and follow-up patients with FH globally. From Asia-Pacific, only 6 countries are participating and no data among Filipinos particularly on genetic profiles is available at present. This study attempts to initiate data collection and participation in the global initiative. OBJECTIVES: Primary: 1. To describe the phenotype of Filipino patients with FH. 2. To determine and characterize the LDL-R gene mutations among Filipino patients with clinical features of FH. Secondary: To determine the association of the clinical characteristics of FH with the presence of LDLR gene mutations. DESIGN: Cross- Sectional Study. SETTING: Multicenter, Outpatient Clinic. PARTICIPANTS: 60 unrelated patients, 18 y/o and above from UP-PGH, Manila Doctors Hospital and Cardinal Santos Medical Center. FH was diagnosed according to the Dutch Lipid Clinic Network Criteria cited by WHO which is based on a history of premature CVD, family history, tendon xanthoma, arcus cornealis, and LDL C levels. METHODS: With informed consent, clinical history, physical examination and lipid profile data were determined. Blood samples were extracted, processed to isolate DNA specimens at the National Institutes of Health, Institute of Human Genetics, and sent to Canterbury Health Laboratories at Christchurch, New Zealand for DNA analysis. ANALYSIS: Descriptive statistics, Fisher's exact test and Student's t-test using Stata version 6.0 software. RESULTS: Sixty patients with a mean age of 55 y/o were included, including 39 (65%) females. The mean LDL level was 227 mg/dl. Cardiovascular Disease and a family history of dyslipidemia were present in 55 & 60% of the samples, respectively. Twenty percent had documented LDL-R gene mutations. Six of the mutations were considered novel. A family history of dyslipidemia, an elevated LDL-C level, and a high FH score exhibited a statistically significant association with mutations. The study population has a high prevalence of CVD at an average age of 55 years with a strong family history of dyslipidemia and very high average LDL-C levels. One out of every 5 patients had LDL-R gene mutations, 6 of which were considered novel. LDL-R gene mutation was significantly associated with family history of dyslipidemia, LDL-C Level and FH score. CLINICAL AND RESEARCH IMPLICATION: This is the first international collaborative genetic study among Filipinos with FH. Data could allow the country to participate in the WHO/MEDPED global program. Collaborative efforts will lead to more effective detection, treatment and prevention of CV events. Novel mutations were discovered and further analysis of these genes will be done.

Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol--a multinational, multicenter, double-blind study.

BACKGROUND AND PURPOSE: There have been few reports on the efficacy and safety of statins in the Asian population. The study objectives were to compare the efficacy and safety of atorvastatin and simvastatin in Asian people. MATERIALS AND METHODS: This was a 16-week, double-blind, double-dummy, randomized, multicenter study involving eight medical centers in six Asian countries or areas. After a 6-week, diet-controlled, placebo lead-in period, 157 patients with low-density lipoprotein cholesterol (LDL-C) of between 160 and 250 mg/dL and serum triglyceride (TG) of less than 400 mg/dL were randomized to receive 10 mg of either atorvastatin (n = 79) or simvastatin (n = 78). After 8 weeks of treatment, all patients had the dose of study medication increased to 20 mg, irrespective of LDL-C concentration. Data obtained by monitoring lipid profiles, adverse events, and laboratory tests during the 16 weeks of study were used to assess the efficacy and safety of both treatments. RESULTS: After 8 weeks of treatment, LDL-C concentrations were reduced by 42.5% from baseline in patients receiving atorvastatin and 34.8% in those receiving simvastatin (p = 0.0006). Patients treated with atorvastatin also had a significantly greater reduction in very-low-density lipoprotein cholesterol (VLDL-C), TG, and total cholesterol (TC) after 8 weeks of treatment. The significantly greater reductions in LDL-C, VLDL-C, TG, and TC from baseline achieved with atorvastatin were still observed after an additional 8 weeks of treatment with 20 mg study medication. Both drugs increased high-density lipoprotein cholesterol (HDL-C) concentrations after 16 weeks of treatment, with no significant difference between the two treatments. After 16 weeks of treatment, 93% of atorvastatin and 85% of simvastatin patients had achieved their National Cholesterol Education Program LDL-C goals. No deaths occurred in the study population and the incidence of treatment-emergent adverse events was the same in the two groups (28%). Only one patient who was treated with simvastatin had a transaminase or creatine phosphokinase concentration that was more than three-fold the upper limit of normal. CONCLUSIONS: Asian people with primary hypercholesterolemia treated with atorvastatin had lower LDL-C, VLDL-C, TG, and TC after 8 weeks and 16 weeks of treatment than those treated with simvastatin. Both drugs demonstrated acceptable safety profiles.

Socio-demographic factors and the prevalence of metabolic syndrome among filipinos from the LIFECARE cohort.

BACKGROUND: Metabolic syndrome(MetS) is an aggregation of multiple metabolic risk factors shown to lead to the development of cardiovascular disease. The International Diabetes Federation(IDF) and the modified National Cholesterol Education Program Adult Treatment Panel Ⅲ(mNCEP) criteria are used in identifying MetS. This report will determine the prevalence of MetS and its component risk factors of the Philippine cohort of the LIFE course study in CARdiovascular disease Epidemiology(LIFECARE). METHODS: Our study recruited 3,072 participants aged 20-50 years old from Metro Manila and four nearby provinces. Baseline anthropometric and clinical parameters were measured. Prevalence of MetS and its component factors were determined. Associations with socio-demographic factors were determined. RESULTS: The prevalence of MetS was 19.7% and 25.6% by IDF and mNCEP, respectively(kappa 0.83). Both were associated with increasing age, urban residence, and employed status. It was higher in females by IDF and in males by mNCEP. IDF missed 40% of males and 10% of females identified with MetS by mNCEP. More males were identified by the mNCEP as MetS despite relatively normal waist circumference. CONCLUSION: MetS is common in the Philippines among older, educated, and urban residents. The mNCEP criteria identified more MetS than the IDF criteria.

A community-based validation study of the short-form 36 version 2 Philippines (Tagalog) in two cities in the Philippines.

OBJECTIVE: To evaluate the validity and reliability of the Philippines (Tagalog) Short Form 36 Health Survey version 2 (SF-36v2(®)) standard questionnaire among Filipinos residing in two cities. STUDY DESIGN AND SETTING: The official Philippines (Tagalog) SF-36v2 standard (4-week recall) version was pretested on 30 participants followed by formal and informal cognitive debriefing. To obtain the feedback on translation by bilingual respondents, each SF-36v2 question was stated first in English followed by Tagalog. No revisions to the original questionnaire were needed except that participants thought it was appropriate to incorporate "po" in the instructions to make it more polite. Face-to-face interviews of 562 participants aged 20-50 years living in two barangays (villages) in the highly urbanized city of Makati City (Metro Manila) and in urban and rural barangays in Tanauan City (province of Batangas) were subsequently conducted. Content validity, item level validity, reliability and factor structure of the SF-36v2 (Tagalog) were examined. RESULTS: Content validity of the SF-36v2 was assessed to be adequate for assessing health status among Filipinos. Item means of Philippines (Tagalog) SF-36v2 were similar with comparable scales in the US English, Singapore (English and Chinese) and Thai SF-36 version 1. Item-scale correlation exceeded 0.4 for all items except the bathing item in PF (correlation: 0.31). In exploratory factor analysis, the US two-component model was supported. However, in confirmatory factor analysis, the Japanese three-component model fit the Tagalog data better than the US two-component model. CONCLUSIONS: The Philippines (Tagalog) SF-36v2 is a valid and reliable instrument for measuring health status among residents of Makati City (Metro Manila) and Tanauan City (Province of Batangas).