Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project.

BACKGROUND: Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease associated with vascular risk factors. Nowadays, the coronary artery calcium (CAC) is a specific marker of the presence and extent of atherosclerosis. Additionally, CAC is a predictor of future coronary events in asymptomatic individuals diagnosed with subclinical atherosclerosis (CAC > 0). In this study, our aim is to evaluate the participation of two polymorphisms of the PCSK9 gene as genetic markers for developing subclinical atherosclerosis and cardiometabolic risk factors in asymptomatic individuals. METHODS: We analyzed two PCSK9 polymorphisms (rs2479409 and rs615563) in 394 individuals with subclinical atherosclerosis and 1102 healthy controls using real time- polymerase chain reaction (PCR). RESULTS: Under various inheritance models adjusted for different confounding factors, the rs2479409 polymorphism was associated with an increased risk of developing subclinical atherosclerosis (OR = 1.53, P recessive = 0.041). Both polymorphisms were significantly associated with several cardiometabolic parameters. CONCLUSIONS: Our data suggest that rs2479409 polymorphism could be envisaged as a risk marker for subclinical atherosclerosis.

Influenza and Pneumococcal Vaccination in Non-Infected Cardiometabolic Patients from the Americas during the COVID-19 Pandemic. A Sub-Analysis of the CorCOVID-LATAM Study.

BACKGROUND: Influenza vaccination (IV) and Pneumococcus vaccination (PV) are recommended for patients with cardiometabolic diseases. This study aimed to evaluate the immunization rate of ambulatory cardiometabolic patients during the COVID-19 pandemic in the Americas. METHODS: Electronic surveys were collected from 13 Spanish speaking countries between 15 June and 15 July 2020. RESULTS: 4216 patients were analyzed. Mean age 60 (±15) years and 49% females. Global IV rate was 46.5% and PV 24.6%. Vaccinated patients were older (IV = 63 vs. 58 years; PV = 68 vs. 59, p < 0.01) but without gender difference. Vaccination rates were greater in higher-risk groups (65+, diabetics, heart failure), but not in coronary artery disease patients. In the Southern cone, the rate of IV and PV was approximately double that in the tropical regions of the Americas. In a multivariate model, geographic zone (IV = OR 2.02, PV = OR 2.42, p < 0.001), age (IV = OR 1.023, PV = OR 1.035, p < 0.001), and incomes (IV = OR 1.28, PV = OR 1.58, p < 0.001) were predictors for vaccination. CONCLUSIONS: During the COVID-19 pandemic, ambulatory patients with cardiometabolic diseases from the Americas with no evidence of COVID-19 infection had lower-than-expected rates of IV and PV. Geographic, social, and cultural differences were found, and they should be explored in depth.

Antihyperalgesic Effects of Indomethacin, Ketorolac, and Metamizole in Rats: Effects of Metformin.

Preclinical Research Metformin-dependent mechanisms have been implicated in the antinociceptive effect of some non-steroidal anti-inflammatory drugs (NSAIDs). In this study, the effect of local peripheral or systemic administration of metformin on the local peripheral or systemic antinociception induced by indomethacin, ketorolac and metamizole was assessed in the rat carrageenan-induced thermal hyperalgesia model. Rats were injected with carrageenan (1%, 50 µl) into the right hindpaw which reduced paw withdrawal latency, a measure of thermal hyperalgesia. Local peripheral or systemic administration of indomethacin, ketorolac or metamizole dose-dependently reduced carrageenan-induced thermal hyperalgesia. Local peripheral pre-treatment with metformin (800 µg/paw) partially inhibited the anti-hyperalgesic effect of indomethacin (200 µg/paw) and metamizole (200 µg/paw), but not that of ketorolac (200 µg/paw). In contrast, systemic pre-treatment with metformin (200 mg/kg) attenuated the antihyperalgesic effect of metamizole (10 mg/kg), but not that observed with either indomethacin (10 mg/kg) or ketorolac (10 mg/kg). These findings suggest that some but not all NSAIDs have effects mediated by metformin-dependent mechanisms. Drug Dev Res 78 : 98-104, 2017. ©2017 Wiley Periodicals, Inc.

[Factors associated with delay to reperfusion therapy in patients with ST-Segment Elevation Myocardial Infarction in a hospital in the southeast of Mexico]. / Factores asociados con retraso en la terapia de reperfusión en infarto agudo de miocardio con elevación del segmento ST (IMCEST) en un hospital del sureste mexicano.

UNLABELLED: Introduction and subject: The aim of the study was to determine the factors involved in the delayed medical care of patients with ST-Segment Elevation Myocardial Infarction. METHODS: A prospective observational study was conducted in patients admitted to the coronary care unit at Dr. Juan Graham Casasús hospital with a diagnosis of ST-Segment Elevation Acute Myocardial Infarction. In all patients, clinical data, type and time of reperfusion treatment, and factors associated with delay were identified. RESULTS: Between November 2012 and January 2015 we included 213 patients with ST-Segment Elevation Myocardial Infarction. Age, diabetes, atypical chest angina and patient arrival period (night or weekend), were more frequent in patients presenting after 12 hours of onset of symptoms of myocardial infarction. Of these, hospital admission at night or weekend was the only independent predictor for delay to the emergency room. CONCLUSIONS: This study shows that in a referral hospital in southeast of Mexico, the delay attributable to the patient was the most common factor associated with care in patients with ST-Segment Elevation Myocardial Infarction. Patient arrival period was associated with delay to medical care.

Association between Stable Coronary Artery Disease and In Vivo Thrombin Generation.

Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients. Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD. Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 µg/L versus 20.81 µg/L, p = 0.002) and homocysteine (11.36 µmol/L versus 8.81 µmol/L, p < 0.01) compared to the patients without significant CAD. Specifically, in patients with CAD+ the level of TAT level was associated with the severity of CAD being 36.17 ± 24.48 µg/L in the patients with bivascular obstruction and 42.77 ± 31.81 µg/L in trivascular coronary obstruction, p = 0.002. Conclusions. The level of in vivo thrombin generation, quantified as TAT complexes, is associated with the presence and severity of CAD assessed by coronary angiography in stable CAD patients.

The role of gene variants of the inflammatory markers CRP and TNF-α in cardiovascular heart disease: systematic review and meta-analysis.

It is widely acknowledged that cardiovascular heart disease (CHD) has a genetic influence. Several studies have investigated the role of inflammatory markers like C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) in the causation of cardiovascular diseases. Although there have been several positive studies associating CRP and TNF-α genes with CHD, the evidence is not entirely consistent. Therefore, we performed a meta-analysis to gain a better understanding into this issue. The meta-analysis was conducted with 22 articles of genetic association studies of CRP (G1059C rs1800947, C1444T rs1130864, C717T rs2794521 and G3872A rs1205) and TNF-α (C857T rs1799724, C863A rs1800630 and T1031C rs1799964) genes. To analyze the association of these variants with CHD we used the following models: allelic, additive, dominant and recessive. In addition, we performed a sub-group analysis by Caucasian population using the same four models. CRP and TNF-α gene polymorphisms showed a positive significant association with CHD. This study provides evidence that rs2794521 of the CRP gene and rs1799724, rs1800630 and rs1799964 of the TNF-α gene polymorphisms may be risk factors to manifest CHD. The analysis of rs1800947 and rs1205 of the CRP gene yielded a protective effect in the pathogenesis of this disease. Only the analysis of the rs1130864 polymorphism showed a lack of association with CHD. To have conclusive outcomes it is necessary to integrate more studies to confirm our findings.

The Trp719Arg polymorphism of the KIF6 gene and coronary heart disease risk: systematic review and meta-analysis.

BACKGROUND: Genetic factors play an important role in the pathogenesis of coronary heart disease (CHD). Kinesin-like protein 6 (KIF6) is a new candidate gene for CHD, since it has been identified as a potential risk factor. The aim of this study was to perform a systematic review and meta-analysis of previously published association studies between the Trp719Arg polymorphism of KIF6 and the development of CHD. METHODS: Studies and abstracts investigating the relationship between the Trp719Arg polymorphism of KIF6 and subsequent risk for development of CHD were reviewed. Electronic search from Pubmed and EBSCO databases was performed between 1993 and 2014 to identify studies that fulfilled the inclusion criteria. To analyze the association we used the models: allelic, additive, dominant and recessive. Moreover, we conducted a sub-analysis by populations using the same four models. RESULTS: Twenty-three studies were included in the meta-analysis. The Trp719Arg polymorphism showed a significant association with CHD when the analysis comprised the population with myocardial infarction (MI) and the additive genetic model was used. Moreover, this polymorphism showed a protective association with CHD when the analysis comprised the whole population using the recessive genetic model. CONCLUSIONS: Our findings indicate that the Trp719Arg polymorphism of the KIF6 gene is an important risk factor for developing MI and that allele 719Arg may have a protective association to present CHD in all populations. PROSPERO REGISTRATION: CRD42015024602.

Lipoprotein(a) and homocysteine potentiate the risk of coronary artery disease in male subjects.

BACKGROUND: Lipoprotein (Lp(a)) and homocysteine (Hcy) are independent risk factors for coronary artery disease (CAD). Hcy promotes the release of free apo(a) from Lp(a). The high fibrin affinity of free apo(a) inhibits plasminogen binding and plasmin generation. Hyperhomocysteinemia can result from a less active variant of methylene tetrahydrofolate reductase (variant C677T). Because the C677T genotype is estimated to be present in 32.2% of the Mexican population, we took advantage of this prevalence to determine the possible potentiating effect between high plasma Lp(a) and Hcy for increasing the risk of CAD in male patients. METHODS AND RESULTS: First, 222 male patients admitted for coronary angiography were recruited and classified as CAD+ or CAD-. Anthropometric measurements, traditional risk factors, and plasma total Hcy (tHcy) and Lp(a) levels were recorded in both groups. We performed a conditional logistic regression model adjusted for conventional risk factors of CAD and it became clear that Lp(a) ≥30mg/dl was a risk factor for CAD (odds ratio [OR] 5.06, 95% confidence interval [CI] 1.88-13.51, P=0.001), whereas Hcy was not related to CAD (OR 0.44, 95% CI 0.63-2.90, P=0.44). However, when both factors were considered together in an interaction model, high tHcy and high Lp(a) plasma concentrations showed a potentiated effect (OR 10.52, 95% CI 2.18-50.71, P=0.003). CONCLUSIONS: The combination of high Lp(a) and Hcy levels synergistically increases the likelihood of developing CAD in male patients.