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>

Appropriate use of coronary angiogram among service patients at the UP-Philippine General Hospital in the Year 2019

Rationale@#Coronary artery disease (CAD) is the leading cause of death worldwide and coronary angiography (CA) remains the gold standard for its diagnosis. However, proper patient selection for CA is important to avoid unnecessary risks and expense. The American College of Cardiology (ACC), with other major organizations, developed Appropriate Use Criteria (AUC) for CA. AUC assist clinicians in decision making on whether to use the tests according to indications and objectively assess if these tests are appropriately utilized. This is the first study to determine the appropriateness of CA performed and the clinical and angiographic profile among adult service patients in UP-PGH. @*Objectives@#To determine (1) the indications for CA and its appropriateness based on 2012 AUC for Diagnostic Catheterization by the ACC, (2) the clinical profile of patients who underwent CA among adult service patients at UP-PGH and (3) the angiographic profile of these patients. @*Methods@#This cross-sectional study included all CA studies performed on adult service patients from January to December 2019. Demographic and clinical profiles, non-invasive tests, and angiographic findings were collected. The primary outcome determined was the appropriateness of the indications for each CA performed based on AUC scores. Descriptive analysis using frequencies and mean values with standard deviations were used. @*Results@#Among the 515 patients included, majority were males, above 50 years of age, with normal eGFR, presented initially with chest pain, and with a presenting diagnosis of chronic coronary syndrome. Majority of these patients had obstructive CAD (75%), with left anterior descending artery as the most frequently involved vessel. Non-obstructive CAD was found in 11% while normal coronaries were noted in 14% of these patients. Our findings showed that 99.8% of the CA performed were appropriate, of which majority (54%) had an AUC score of A9. STEMI or a suspicion of STEMI, with an A9 score, was the most frequently encountered indication at 33% of the time. @*Conclusion@#Majority (99%) of the CA studies performed in the PGH cardiac catheterization laboratory for the year 2019 were executed based on highly appropriate indications (AUC scores A7 to A9) and followed Class I and II recommendations from guidelines. The allocation of resources is deemed to be well-utilized based on the data generated from this study.

Clinical Profile and Major Adverse Cardiovascular Outcomes in Patients who Underwent Coronary Revascularization for Left Main Coronary Artery Disease and Left Main Equivalent Coronary Artery Disease in a Tertiary Hospital

@#BACKGROUND: Percutaneous coronary intervention (PCI) for left main (LMCA) coronary artery disease (CAD) was found to be non-inferior and had similar major adverse cardiovascular events (MACE) to coronary artery bypass grafting (CABG). In the local setting, the clinical profile and MACE of patients who underwent either revascularization are, however, unknown. OBJECTIVES: To determine the clinical profile and in-hospital MACE of patients who underwent revascularization (PCI or CABG) for LMCA and left main equivalent CAD. METHODS: This is a prospective descriptive study. Clinical profile and in-hospital, 30-days and 90-days post revascularization MACE were determined. RESULTS: Thirty-seven (37) adults were included. Most were males, diabetics, dyslipidemics, smokers, with previous cardiovascular events and premature CAD. Hypertension was significantly prevalent in the CABG group (PCI=62.50% vs CABG=90.48%, p=0.04). Patients who underwent CABG mostly presented with stable angina (p=0.0453). The majority of the PCI (68.75%) was done as an emergent/urgent procedure, with clear indications for PCI (i.e. STEMI). In-hospital all-cause mortality was significantly higher in the PCI group (PCI=50% vs CABG=0%, p<<0.05). CONCLUSION: Patients with LMCA and left main equivalent CAD were mostly males and had traditional CAD risk factors. In-hospital mortality was significantly higher among the PCI group; however, those who underwent PCI were unstable and unlikely to be good surgical candidates for CABG.

Should anticoagulation be used in the treatment of severe COVID-19?

Background@#The progression of COVID-19 to its acute (pneumonia) phase occurs during the 7th to 14th day of illness. During this highly inflammatory phase, a proportion of patients with severe COVID-19 develop a hypercoagulable state associated with poor prognosis. Hence, anticoagulation is seen as a potentially beneficial intervention due to its antithrombotic effect, anti-inflammatory function, and anti-viral properties. @*Objective@#This review aims to determine the efficacy and safety of anticoagulation in severe COVID-19. @*Methods@#A rapid review was done on April 11, 2020 and updated on April 23, 2020. PubMed, MEDLINE, and medRxiv.org were searched. The review included studies on the association between the use of anticoagulants on top of other interventions, and disease progression and/or mortality among adults >18 years old with severe COVID-19 infection, as well as studies on patients with disseminated intravascular coagulopathy (DIC) of sepsis investigating bleeding complications with anticoagulant use. Four ongoing registered clinical trials on anticoagulants for COVID-19 were also found. @*Results@#Current evidence shows that the use of low-molecular weight heparin (LMWH) in COVID-19 is associated with the following: (1) improved surrogate markers for disease progression (increase in lymphocyte & platelet counts and decrease in D-dimer, fibrinogen degradation products, and IL-6); and (2) reduced 28-day mortality in high risk patients. Studies on DIC related to bacterial sepsis did not show significant increase in bleeding complications with anticoagulation. @*Conclusion@#The use of anticoagulants appears to be beneficial for severe COVID-19 due to a reduction in 28-day mortality and improvement in inflammatory and coagulation markers. However, these findings come from low-quality studies, and confirmation of the effect is needed through randomized controlled trials.

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>

Association of the platelet-lymphocyte ratio (PLR) with outcomes in patients admitted for acute coronary syndrome: The PLACS study

@#<p style="text-align: justify;"><strong>INTRODUCTION: </strong>Patients with acute coronary syndrome (ACS) exhibit a wide spectrum of early risk of death (one to 10 percent). High platelet counts may indicate a propensity for platelet-rich thrombi. Lymphocyte counts drop during ACS due to stress-induced cortisol release. Combining these two markers, recent studies have found that the platelet-tolymphocyte ratio (PLR) is associated with adverse cardiac events among patients with ACS, but local data is limited. The objective of this study is to determine if an elevated PLR taken on admission is associated with higher rates of adverse cardiac events.</p><p style="text-align: justify;"><strong>METHODS:</strong> A retrospective cohort of adult patients with ACS admitted at the UP-Philippine General Hospital was analyzed. Leukocyte and platelet counts were measured by an automated hematology analyzer. The PLR values of these patients were computed, and they were stratified into two groups after determining the optimal cut-off from the receiver operating characteristic curve (ROC) curve. The primary outcome was in-hospital mortality. Secondary outcomes included development of heart failure, cardiogenic shock, reinfarction, and significant arrhythmias.</p><p style="text-align: justify;"><strong>RESULTS:</strong> A total of 174 Filipinos with ACS were included. In-hospital mortality occurred in 30 patients (17%). These patients had a higher PLR compared to those who were discharged alive (p-value <0.0001). The optimal cutoff value of PLR to predict in-hospital mortality is 165, with a sensitivity of 77% and specificity of 70% (area under the ROC curve of 0.766). On multiple logistic regression analysis, a high PLR was an independent predictor of in-hospital mortality (RR 8.52; p 0.003) after controlling for the effect of other variables. The development of the predetermined secondary outcomes did not correlate with PLR on multivariate analysis.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> Among Filipino patients with ACS, an elevated PLR taken within 24 hours of admission is a useful marker to predict in-hospital mortality, thus providing vital information for risk stratification and more aggressive management strategies.</p>

Association of the platelet-lymphocyte ratio (PLR) with outcomes in patients admitted for acute coronary syndrome: The PLACS study

INTRODUCTION: Patients with acute coronary syndrome (ACS) exhibit a wide spectrum of early risk of death (one to 10 percent). High platelet counts may indicate a propensity for platelet-rich thrombi. Lymphocyte counts drop during ACS due to stress-induced cortisol release. Combining these two markers, recent studies have found that the platelet-tolymphocyte ratio (PLR) is associated with adverse cardiac events among patients with ACS, but local data is limited. The objective of this study is to determine if an elevated PLR taken on admission is associated with higher rates of adverse cardiac events.METHODS: A retrospective cohort of adult patients with ACS admitted at the UP-Philippine General Hospital was analyzed. Leukocyte and platelet counts were measured by an automated hematology analyzer. The PLR values of these patients were computed, and they were stratified into two groups after determining the optimal cut-off from the receiver operating characteristic curve (ROC) curve. The primary outcome was in-hospital mortality. Secondary outcomes included development of heart failure, cardiogenic shock, reinfarction, and significant arrhythmias.RESULTS: A total of 174 Filipinos with ACS were included. In-hospital mortality occurred in 30 patients (17%). These patients had a higher PLR compared to those who were discharged alive (p-value CONCLUSION: Among Filipino patients with ACS, an elevated PLR taken within 24 hours of admission is a useful marker to predict in-hospital mortality, thus providing vital information for risk stratification and more aggressive management strategies.