A genetic polymorphism in GCKR may be associated with low high-density lipoprotein cholesterol phenotype among Filipinos: A case-control study

@#<p style="text-align: justify;"><strong>Background.</strong> Low levels of high-density lipoprotein cholesterol (HDL-c) is a well-recognized risk factor in the development of cardiovascular diseases. Associated gene variants for low HDL-c have already been demonstrated in various populations. Such associations have yet to be established among Filipinos who reportedly have a much higher prevalence of low HDL-c levels compared to other races.</p><p style="text-align: justify;"><strong>Objective.</strong> To determine the association of selected genetic variants and clinical factors with low HDL-c phenotype in Filipinos.</p><p style="text-align: justify;"><strong>Methods.</strong> An age- and sex-matched case-control study was conducted among adult Filipino participants with serum HDL-c concentration less than 35 mg/dL (n=61) and those with HDL-c levels of more than 40 mg/dL (n=116). Genotyping was done using DNA obtained from blood samples. Candidate variants were correlated with the low HDL-c phenotype using chi-squared test and conditional logistic regression analysis.</p><p style="text-align: justify;"><strong>Results.</strong> Twelve single nucleotide polymorphisms (SNPs) were associated with low HDL-c phenotype among Filipinos with univariate regression analysis. The variant rs1260326 of glucokinase regulator (GCKR) (CT genotype: adjusted OR=5.17; p-value=0.007; TT genotype: adjusted OR=6.28; p-value=0.027) remained associated with low HDL-c phenotype, together with hypertension and elevated body mass index, after multiple regression analysis.</p><p style="text-align: justify;"><strong>Conclusion.</strong> The variant rs1260326 near GCKR is associated with low HDL-c phenotype among Filipinos. Its role in the expression of low HDL-c phenotype should be further investigated prior to the development of possible clinical applications.</p>

Variants near CETP, MTTP and BUD13-ZPR1-APOA5 may be nominally associated with poor statin response among Filipinos

@#<p style="text-align: justify;"><strong>Objective.</strong> Several studies showed that genetic factors affect responsiveness to statins among different populations. This study investigated the associations of candidate genetic variants with poor response to statins among Filipinos.</p><p style="text-align: justify;"><strong>Methods.</strong> In this unmatched case-control study, dyslipidemic participants were grouped into statin responders and poor responders based on the degree of reduction in LDL-c from baseline. DNA from blood samples were genotyped and analyzed. The association of candidate variants with statin response was determined using chi-square and logistic regression analysis.</p><p style="text-align: justify;"><strong>Results.</strong> We included 162 adults on statins (30 poor responders as cases, 132 good responders as controls). The following variants are nominally associated with poor response to statin among Filipinos at a per-comparison error rate of 0.05: rs173539 near CETP (OR=3.05, p=0.015), rs1800591 in MTTP (OR=3.07, p=0.021), and rs1558861 near the BUD13-ZPR1-APOA5 region (OR=5.08, p=0.004).</p><p style="text-align: justify;"><strong>Conclusion.</strong> Genetic variants near CETP, MTTP and the BUD13-ZPR1-APOA5 region are associated with poor response to statins among Filipinos. Further study is recommended to test the external validity of the study in the general Filipino population.</p>

Prognostic impact of coronary collaterals in acute coronary syndrome (PICC-ACS): A meta-analysis of observational studies

@#<p style="text-align: justify;"><strong>INTRODUCTION:</strong> The coronary collateral circulation (CCC) is an alternative source of blood supply in coronary artery disease (CAD). The prognostic value of the presence of CCC at the time of acute coronary syndrome (ACS) is undefined with regards to hard outcomes, particularly reduction in mortality. The study's aim is to determine if the presence of CCC demonstrated by coronary angiography during an ACS is associated with a reduction in mortality. </p><p style="text-align: justify;"><strong>METHODS:</strong> We conducted a systematic search of studies using MEDLINE, EMBASE, ScienceDirect, Scopus, and Cochrane Central Register of Controlled Trials databases in all languages and examined reference lists of studies. The inclusion criteria were 1) observational; 2) population included adults >19 years old with an acute coronary syndrome; 3) reported data on mortality in association with the presence or absence of CCC on angiography; and 4) should have controlled for confounders by using logistic regression analysis. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale for observational studies. The outcome of interest was reduction in all-cause mortality, assessed using Mantel-Haenzel analysis of random effects to compute for risk ratios.</p><p style="text-align: justify;"><strong>RESULTS:</strong> Pooled analysis from 11 identified trials with 8,370 subjects showed that among patients with ACS who underwent coronary angiography, the presence of CCC showed a trend towards benefit in terms of mortality, but was not statistically different from those without CCC [RR 0.65, (95% CI 0.38 to 1.12), p<0.0001, I2=74%]. In those ACS patients with CCC treated with PCI, a significant reduction in mortality was found [RR 0.43, (95% CI 0.29 to 0.64), p< 0.0001, I2=0%].</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> The presence of CCC during ACS showed a trend towards mortality reduction. Further, among patients treated with PCI, those with CCC had an incrementally significant reduction in mortality compared to those without CCC.</p>

Four-year clinical outcomes of Filipino patients with or at risk for atherothrombotic events from the REACH registry

@#<p style="text-align: justify;"><strong>INTRODUCTION: </strong>Patients with established atherothrombotic disease (EAD) or those with only atherothrombotic risk factors are at high risk for cardiovascular events and death. There are scant data on the clinical profile of stable Filipino patients with or at risk for atherothrombosis and their long-term outcomes. The authors'objective is to present the baseline clinical profile and four-year cardiovascular outcomes in Filipino outpatients with EAD and those with multiple atherothrombotic risk factors in comparison to the Asian and Global populations</p><p style="text-align: justify;"><strong>METHODS:</strong> The Reduction of Atherothrombosis for Continued Health (REACH) registry is an international, prospective cohort of 68,236 patients aged at least 45 years old with either EAD or at least three atherothrombotic risk factors enrolled from 44 countries in 2003-2004. The Philippine cohort consists of 1040 outpatients with EAD (N=913) or at least three atherothrombotic risk factors (N=127) consecutively enrolled and followed up for at least one to four years for the occurrence of cardiovascular death (CVD), myocardial infarction (MI) and stroke.</p><p style="text-align: justify;"><strong>RESULTS:</strong> Nine hundred fifty-five Filipino outpatients (96)% completed the four-year follow-up. Mean age is 65.5 years with similar sex distribution. Common risk factors included diabetes (46%), hypertension (87.4%), hypercholesterolemia (62.9%), and smoking history (29.7%). Ninety-two percent had EAD-- 43% with coronary artery disease, 45% with cerebrovascular disease (CVD) and four percent with peripheral artery disease (PAD). The combined primary endpoint of CVD/MI/stroke was 14.7%, but higher (19.8%) among those with polyvascular disease. Cerebrovascular disease (CVD) patients had the highest CVD/MI/stroke rates (17.6%); PAD patients had the highest CVD/MI/stroke and hospitalization rate (33.2%). Baseline medication usage is 81.1% for antiplatelet agents, 62.6% for statins and 69% for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker but four-year follow-up medication usage rates were lower.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> Filipino outpatients with or at risk for atherothrombosis experienced high long-term rates of CV events. This is the first report of long-term cardiovascular outcomes of stable Filipino outpatients with this high-risk profile.</p>