Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score

ABSTRACT Objective Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. Materials and methods Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. Results Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. Conclusion Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.

The TIMI risk score for STEMI predicts in-hospital mortality and adverse events in patients without cardiogenic shock undergoing primary angioplasty / La escala de riesgo TIMI para infarto del miocardio con elevación del segmento ST predice mortalidad y eventos adversos intrahospitalarios en pacientes sin choque cardiogénico sometidos a angioplastía coronaria

Introduction: Patients with ST elevation acute myocardial infarction (STEMI) comprise a heterogeneous population with respect to the risk for adverse events. Primary percutaneous coronary intervention (PCI) has shown to be better, mainly in high-risk patients. Objective: The purpose of this study was to determine if the Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI applied to patients undergo primary PCI identifies a group of patients at high risk for adverse events. Methods: We identifed patients with STEMI without cardiogenic shock on admission, who were treated with primary PCI. The TIMI and CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) risk scores were calculated to determine their predictive value for in hospital mortality. Patients were divided into two groups according to their TIMI risk score, low risk being 0-4 points and high risk ≥5 points, and the frequency of adverse events was analyzed. Results: We analyzed 572 patients with STEMI. The c-statistics predictive value of the TIMI risk score for mortality was 0.80 (p=0.0001) and the CADILLAC risk score was 0.83, (p=0.0001). Thirty-two percent of patients classifed as high risk (TIMI ≥5) had a higher incidence of adverse events than the low-risk group: mortality 14.8% vs. 2.1%, (p=0.0001); heart failure 15.3% vs. 4.1%, (p=0.0001); development of cardiogenic shock 10.9% vs. 1.5%, (p=0.0001); ventricular arrhythmias 14.8% vs. 5.9%, (p=0.001); and no-refow phenomenon 22.4% vs. 13.6%, (p=0.01). Conclusions: The TIMI risk score for STEMI prior to primary PCI can predict in hospital mortality and identifes a group of high-risk patients who might develop adverse events.

Introducción: Los pacientes con infarto agudo del miocardio con elevación del segmento ST (IAM CEST), son una población heterogénea por lo que toca al riesgo de eventos adversos. La intervención coronaria percutánea (ICP) primaria mostró ser mejor, principalmente en los pacientes de riesgo alto. Objetivo: La propuesta de este estudio fue determinar si la escala de riesgo de trombólisis en infarto del miocardio (TIMI) para IAM CEST, aplicado a los pacientes sometidos a ICP primaria, identifica a grupos de pacientes de riesgo alto de eventos adversos. Métodos: Se identificaron a pacientes con IAM CEST sin choque cardiogénico al ingreso, quienes fueron tratados con ICP primaria. Se calcularon las escalas de riesgo TIMI y CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications), para determinar su valor predictivo de mortalidad intrahospitalaria. Los pacientes se dividieron en dos grupos de acuerdo a su escala de riesgo TIMI, riesgo bajo con 0-4 puntos y riesgo alto con ≥5 puntos, se analizó la frecuencia de eventos adversos. Resultados: Se analizaron 572 pacientes con IAM CEST. El valor predictivo del estadístico C de la escala de riesgo TIMI para mortalidad fue de 0.80 (p=0.0001), y la escala de riesgo CADILLAC fue de 0.83, (p=0.0001). El 32% de los pacientes clasificados como riesgo alto (TIMI ≥5), tuvo una alta incidencia de eventos adversos comparada con el grupo de riesgo bajo: la mortalidad 14.8% vs. 2.1%, (p=0.0001); falla cardiaca 15.3% vs. 4.1%, (p=0.0001); desarrollo de choque cardiogénico 10.9% vs. 1.5%, (p=0.0001); arritmias ventriculares 14.8% vs. 5.9%, (p=0.001), y fenómeno de no reflujo 22.4% vs. 13.6%, (p=0.01). Conclusiones: La escala de riesgo TIMI para IAM CEST, previo a ICP primaria puede predecir mortalidad intrahospitalaria e identificar a un grupo de pacientes de riesgo alto, los cuales pueden desarrollar eventos adversos.