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.

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.

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.

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.).

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.

Prevalence of cardiovascular risk factors in relation to socio-demographic profile of the life course study in cardiovascular disease epidemiology study (LIFECARE) Philippine cohort

OBJECTIVE: To describe the distribution of the clinical cardiovascular risk profile of the LIFECARE Philippine cohort in relation to its socio-demographic factors. METHODS: We recruited a total of 3,072 apparently healthy participants from Manila and nearby provinces of Rizal, Batangas, Bulacan and Quezon. Face-to-face interview was done to obtain socio-demographic data. Baseline clinical parameters and biochemical tests were obtained. Prevalence of cardiovascular risk factors was determined by sex, place of residence, level of education and employment. RESULTS: Overall prevalence of diabetes mellitus was at 5%, similar between sexes, area class, educational attainment and employment status. More smokers were male, employed or with an elementary level of education. Prevalence of hypertension was at 14.5% and was seen more in males, urban dwellers, employed or with an elementary level of education. Dyslipidemia was seen more in males, living in the rural areas, employed or with a college level of education. Lastly, obese participants were seen more in females, living in urban areas, employed with a college level of eduction. CONCLUSION: Older, male and employed participants who are living in the urban areas have more cardiovascular risk factors.

"You are what you eat:" Self-reported preferences for food taste and cooking methods of adult Filipinos (20-50 years old)

OBJECTIVE: To describe the self-reported preferences for food taste and cooking methods of adult Filipinos (20-50 years old). METHODS: This is a cross-sectional community survey of 3,072 adults from Metro Manila, Bulacan, Batangas, Quezon, Rizal. RESULTS AND CONCLUSION: There were differences in preferred tastes of males (food that tasted "just right", spicy) vs. females (salty); younger adults (sweet, spicy) vs. older adults (bland); urban (salty, spicy) vs. rural adults ("just right") adults with higher education (sweet, salty, spicy) vs. those with less schooling who liked food which tasted "just right." Smokers preferred spicy taste vs. non-smokers who liked sweet-tasting food. Adults who reported having had alcohol intake preferred spicy food. Those who reported feeling stressed liked savoury taste (sweet, salty) while those who were not stressed liked food which tasted "just right." Cooking with oil was the usual and the most preferred cooking method. Younger adults and smokers liked to use oil in cooking. Food which tasted "just right"/moderate was most preferred by adult Filipinos with hpertension or MeTS. Diabetics did not prefer sweet tasting food. More diabetics (p=0.05) and those with MeTS (p=0.003) usually use other cooking methods instead of frying. Eliciting self-reported taste preferences as well as the usual and preferred cooking methods is important for nutritional management and relevant lifestyle advice which healthcare providers should incorporate in their management of patients, especially those with hypertension, diabetes, and metabolic syndrome.

Where we are: socio-ecological and health profile of the Philippine LIFEcourse study in CARdiovascular disease epidemiology (LIFECARE) study sites

OBJECTIVE: This study aims to describe the socio-ecological and health profile of the Philippine LIFECARE study sites, its health care services and leading causes of mortality and morbidity. METHODS: This is a prospective cohort study that recruited participants aged 20-50 years from Metro Manila and four provinces (Bulacan, Batangas, Quezon, Rizal). Study sites were characterized according to their geographical area, terrain and environmental profile, and available health care system. RESULTS: 3,072 subejects were included, with male-to-female ratio of 1:1.3 and majority aged 30-50 years. Metro Manila was the most congested site. Two-thirds of the 62 villages (barangays) were rural, outside the town proper, and in lowlands. One-fourth were along coastal area. Almost all were accessible by public transportation. Majority have reduced forest cover, but were relatively safe from environmental hazards. Rural health units, hospitals, and professional health care workers were concentrated in Metro Manila. Leading cause of morbidity was respiratory tract infection, while cardiovascular diseases caused most of mortalities. CONCLUSION: Study sites were mainly rural, outside the town proper and in lowlands, with available public transportation. There is an unequal distribution of health resources. Cardiovascular diseases is still the leading cause of mortality. The disparities in geographical access to health care play an important role in shaping human health.

Who we are: Demographic and stress profile of the Philippine LIFECARE cohort

OBJECTIVE: To describe the demographic and stress profile of the participants in the LIFECARE cohort. METHODS: The Life Course Study in Cardiovascular Disease Epidemiology (LIFECARE) is a community-based prospective cohort of apparently healthy individuals aged 20 to 50 years old with no preexisting cardiovascular disease. The second phase out of four phases of study involves collection of baseline socio-demographic, anthropometric, biochemical and cardiovascular parameters and stress profiles. It was conducted via face-to-face interview using a survey questionnaire. RESULTS AND CONCLUSION: A total of 3072 participants from Metro Manila and 4 provinces in Luzon were recruited. The female to male ratio was 1.3:1. Majority of the participants were aged 30 years old and above. Most were married, employed and literate. Majority attained at least high school level of education. Loss of job was the most common stressor experienced in the past year. Majority of the cohort reported occasional experience of general stress and moderate level of financial stress. Occurrence of general stress within the past year was higher among females (p < 0.001), younger age-group (p=0.006), and among those who reached college level of education (p<0.001). Furthermore, level of current financial stress was high to severe among older age-group (p=0.004), and among widow/widower/separated (p<0.0001). While the relationship between psychosocial stress and physical illness had not been established in this study, there is a need to investigate demographics and psychosocial stress, and their implications in increasing adverse health outcomes in general, and cardiovascular risk in particular.

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).

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 incidence of type 2 diabetes mellitus in the Philippines: a 9-year cohort study.

AIMS: Currently, there are no available data on the incidence of type 2 diabetes mellitus (T2DM) in the Philippines. A cohort derived from a national study population (FNRI-NNS, 1998) was revisited after 9 years to yield valuable data on glucose homeostasis among Filipinos. METHODS: Six out of 13 national regions were included in the cohort. There were 1749 out of 2122 respondents (82.4%). 1386 (95.9%) consented to a fasting blood glucose (FBG) test, and 1275 (88.2%) completed the 2h post-glucose (2HPG) load determination using whole blood capillary samples. RESULTS: We observed a significant increase of mean FBGs (91.5mg/dL to 103.3mg/dL) from 1998 to 2007. The 9-year incidence of T2DM was 16.3%. The prevalence of T2DM was 28.0%. The prevalence of pre-diabetes, i.e., combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) was 31.3%; IFG was 17.5% and IGT was 23.9%. CONCLUSIONS: The study shows the alarming growth of diabetes, IFG, and IGT in our country that warrants early aggressive intervention for prevention and management. We encourage the use of 2h post-glucose load aside from FBG in screening for true diabetics, IFGs, and IGTs.

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.

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.

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.