Validation of the SCORE2 risk prediction algorithm in a Portuguese population: A new model to estimate 10-year cardiovascular disease incidence in Europe.

INTRODUCTION AND OBJECTIVES: Subjects without cardiovascular (CV) disease (CVD) may suffer from subclinical atherosclerosis, and are at increased risk for atherosclerotic CV events (ASCVE). The ESC/EAS risk SCORE was updated by SCORE2, which estimates 10-year risk of fatal and non-fatal CVD in European populations aged 40-69 years without established CVD or diabetes. Our aim was to compare the two ESC/EAS risk scores and to validate SCORE2 in our population. METHODS: A total of 1071 individuals (age 57.2±6.1 years; 75.2% male) without CVD or diabetes, from GENEMACOR study controls, were analyzed over 5.4±3.9 years. The population was stratified into risk categories according to the two scores, and the area under the ROC curve (AUC) and Harrell's C-index assessed the scores' performance. Calibration was performed using the goodness-of-fit test, and occurrence of the first event assessed by Cox regression. Kaplan-Meier analysis estimated SCORE2 survival. RESULTS: SCORE stratified subjects into four risk categories: low (7.4%), moderate (46.5%), high (25.3%) and very high (20.8%), and SCORE2 into three: low-to-moderate (24.7%), high (59.0%) and very high (16.2%). SCORE presented good discrimination for CV mortality (AUC=0.838; C-index=0.834, 95% CI: 0.728-0.940), as did SCORE2 for total CV events (AUC=0.744; C-index=0.728, 95% CI: 0.648-0.808). Calibration did not show a disparity between observed and expected ASCVE. The probability of ASCVE was eight times higher in very-high-risk SCORE2 (p=0.001), and three times in the high-risk group (p=0.049). Event-free survival was 99%, 90% and 72% in the low-to-moderate, high and very-high-risk categories, respectively (p<0.0001). CONCLUSIONS: SCORE2 improved population stratification by identifying higher-risk patients, enabling early preventive measures. It showed good discriminative ability for all ASCVE.

Predictive improvement of adding coronary calcium score and a genetic risk score to a traditional risk model for cardiovascular event prediction.

AIMS: Coronary artery calcium score (CACS) and polygenic risk score have been used as novel markers to predict cardiovascular (CV) events of asymptomatic individuals compared with traditional scores. No previous studies have directly compared the additive capacity of these two markers relative to conventional scores. The aim of the study was to evaluate the change in CV risk prediction ability when CACS, genetic risk score (GRS), or both are added to Systematic Coronary Risk Evaluation 2 (SCORE2). METHODS AND RESULTS: In a prospective, observational population-based study, 1002 asymptomatic subjects (mean age 53.1 ± 6.8 years, 73.8% male), free of clinical coronary disease and diabetes, were selected from GENEMACOR-study controls. SCORE2, CACS, and GRS were estimated to evaluate CV events' predictive and discriminative ability through Harrell's C-statistics. Net reclassification improvement (NRI) and integrated discrimination index were used to reclassify the population. Multivariable Cox proportional hazard ratio (HR) analysis assessed the variables independently associated with CV events. C-statistic demonstrated that the discriminative value for CV event occurrence was 0.608 for SCORE2, increasing to 0.749 (P = 0.001) when CACS was added, and improved to 0.802 (P = 0.0008) with GRS, showing a better discriminative capacity for CV events. Continuous NRI reclassified >70% of the population. Cox proportional analysis showed that the highest categories of SCORE2, CACS, and GRS remained in the equation with an HR of 2.9 (P = 0.003), 5.0 (P < 0.0001), and 3.2 (P = 0.003), respectively, when compared with the lowest categories. CONCLUSION: In our population, CACS added to SCORE2 had better ability than GRS in CV event risk prediction, discrimination, and reclassification. However, adding the three scores can become clinically relevant, especially in intermediate-risk persons.

Our study highlights the impact of including coronary artery calcium score (CACS) and genetic risk score (GRS) alongside Systematic Coronary Risk Evaluation 2 (SCORE2) for enhancing cardiovascular (CV) risk assessment in primary prevention. In our population, adding CACS to SCORE2 exhibited a superior discriminative capacity for CV events compared with GRS alone in terms of risk prediction, discrimination, and reclassification. Our results emphasize the potential clinical relevance of using all three scores to identify high-risk individuals who would benefit from earlier and more stringent cardiovascular risk management strategies to prevent future cardiovascular events.

Epicardial Adipose Tissue: The Genetics Behind an Emerging Cardiovascular Risk Marker.

Evidence points epicardial adipose tissue (EAT) as an emerging cardiovascular risk marker. Whether genetic polymorphisms linked with atherosclerosis are associated with higher EAT is still unknown. We aim to assess the role of genetic burden of atherosclerosis and its association to EAT in a cohort of asymptomatic individuals without coronary disease. A total of 996 participants were prospectively enrolled in a single Portuguese center. EAT volume was measured by Cardiac Computed Tomography and participants were distributed into 2 groups, above and below median EAT. SNPs were genotyped and linked to their respective pathophysiological axes. A multiplicative genetic risk score (mGRS) was constructed, representing the genetic burden of the studied SNPs. To evaluate the association between genetics and EAT, we compared both groups by global mGRS, mGRS by functional axes, and SNPs individually. Individuals above-median EAT were older, had a higher body mass index (BMI) and higher prevalence of hypertension, metabolic syndrome, diabetes, and dyslipidemia. They presented higher GRS, that remained an independent predictor of higher EAT volumes. The group with more EAT consistently presented higher polymorphic burden across numerous pathways. After adjustment, age, BMI, and mGRS of each functional axis emerged as independently related to higher EAT volumes. Amongst the 33 SNPs, MTHFR677 polymorphism emerged as the only significant and independent predictor of higher EAT volumes. Patients with higher polymorphism burden for atherosclerosis present higher EAT volumes. We present the first study in a Portuguese population, evaluating the genetic profile of EAT through GWAS and GRS, casting further insight into this complicated matter.

KAsH: A new tool to predict in-hospital mortality in patients with myocardial infarction.

INTRODUCTION: Complex risk scores have limited applicability in the assessment of patients with myocardial infarction (MI). In this work, the authors aimed to develop a simple to use clinical score to stratify the in-hospital mortality risk of patients with MI at first medical contact. METHODS: In this single-center prospective registry assessing 1504 consecutively admitted patients with MI, the strongest predictors of in-hospital mortality were selected through multivariate logistic regression. The KAsH score was developed according to the following formula: KAsH=(Killip class×Age×Heart rate)/systolic blood pressure. Its predictive power was compared to previously validated scores using the DeLong test. The score was categorized and further compared to the Killip classification. RESULTS: The KAsH score displayed excellent predictive power for in-hospital mortality, superior to other well-validated risk scores (AUC: KAsH 0.861 vs. GRACE 0.773, p<0.001) and robust in subgroup analysis. KAsH maintained its predictive capacity after adjustment for multiple confounding factors such as diabetes, heart failure, mechanical complications and bleeding (OR 1.004, 95% CI 1.001-1.008, p=0.012) and reclassified 81.5% of patients into a better risk category compared to the Killip classification. KAsH's categorization displayed excellent mortality discrimination (KAsH 1: 1.0%, KAsH 2: 8.1%, KAsH 3: 20.4%, KAsH 4: 55.2%) and better mortality prediction than the Killip classification (AUC: KAsH 0.839 vs. Killip 0.775, p<0.0001). CONCLUSION: KAsH, an easy to use score calculated at first medical contact with patients with MI, displays better predictive power for in-hospital mortality than existing scores.

Diabetes e doença cardiovascular: prognóstico após cinco anos de revascularização percutânea / Diabetes and cardiovascular disease: prognosis five years after percutaneous revascularization

Fundamentos: O diabetes mellitus (DM) é reconhecidamente fator de risco cardiovascular. Sabendo-se que a intervenção coronariana percutânea (ICP) melhora o prognóstico da doença coronariana (DC), pretendemos verificar se esse efeito é similar em doentes diabéticos (D) e não diabéticos (ND). Objetivo: Analisar o prognóstico em longo prazo do DM em pacientes submetidos a ICP. Métodos: Estudo de coorte, unicêntrico, retrospectivo, envolvendo pacientes consecutivos submetidos à ICP, eletiva ou de urgência, entre janeiro 2002 e dezembro 2003. Definiram-se dois grupos: pacientes com DM (D) e sem DM (ND). compararam-se as variáveis clínicas e angiográficas da ICP com resultado clínico ao final de cinco anos. Definiram-se como eventos maiores cardiovasculares (EMC): morte, nova síndrome coronariana aguda, acidente vascular encefálico (AVE) e nova revascularização cirúrgica ou ICP. Foram ainda avaliadas as taxas de trombose de stent, revascularização do vaso-alvo (RVA) e revascularização da lesão-alvo (RLA). Resultados: O seguimento em cinco anos foi 94%. Foram realizadas 446 ICP em 406 pacientes, média de idade=63,0+-11 anos, 70,4% masculino. Destes, 128 (31,5%) eram do grupo D. Em cinco anos o valor de EMC foi 50,7% para D e 36,7% para N. Encontrou-se mortalidade global...

Independent association of the variant rs1333049 at the 9p21 locus and coronary heart disease.

INTRODUCTION: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. AIM: To investigate whether the SNP rs1333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. METHODS: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.71 +/- 8.9 years, 79.9% male and 683 controls without coronary disease (mean age 53.3 +/- 10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. RESULTS: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR = 1.33; p = 0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR = 1.34, p = 0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR = 1.05, p = 0.670). After logistic regression analysis, the CC genotype remained in the equation with OR = 1.7; p = 0.018 and CG with OR = 1.5, p = 0.048. CONCLUSION: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.

Cardiomiopatia dilatada por virus H1N1 / Dilated cardiomyopathy due to H1N1 virus

Mulher de 58 anos, sem antecedentes médicos relevantes, apresenta infecção respiratória pelo vírus H1N1, requerendo internação na Unidade de Cuidados Intensivos. Após a alta, refere progressiva astenia e dispneia, sendo internada nove meses depois por derrame pleural e infecção respiratória. Avaliação específica pela Cardiologia revela cardiomiopatia dilatada com má função sistólica do ventrículo esquerdo, compatível com miocardite. A ressonância magnética se apresenta compatível com miocardite. Dados os antecedentes e havendo sido descartada doença autoimune e tóxica, associou-se a doença ao vírus H1N1. O prognóstico é muito positivo, com recuperação quase total da função do ventrículo esquerdo.

A 58-year-old woman with no relevant prior medical conditions presented a respiratory infection caused by theH1N1 virus, requiring admittance to an Intensive Care Unit. After discharge, the patient complained of progressiveasthenia and dyspnea, being hospitalized nine months later with a diagnosis of pleural effusion and respiratory infection. Further evaluation by the Cardiology Unit revealed dilated cardiomyopathy with poor systolicfunction of the left ventrícle, compatible with myocarditis. A cardiac magnetic ressonance examination was compatible with myocarditis. Given her previousadmittance and having ruled out toxic aspects and autoimmune disease, the disease was associated with the H1N1 virus. The prognosis is very positive, with almost complete recovery of the left ventricular function.

Coronary artery bypass grafting in octogenarians: long-term results.

INTRODUCTION: As surgical revascularization is becoming more frequent in octogenarians, we reviewed our data to analyze the impact of coronary artery bypass grafting on short- and long-term morbidity and mortality. METHODS: We performed a retrospective study of 101 consecutive patients aged 80 years or older, who underwent coronary artery bypass in a single cardiac center between January 2002 and December 2007. The patients were divided into two groups: off-pump (64.4%) and on-pump (35.6%), depending on whether the surgery was performed with cardiopulmonary bypass. Early results and those up to 6 years after surgery were assessed. RESULTS: Baseline characteristics were similar between the groups and follow-up was 90% complete. There were no significant differences between groups in mean age (off-pump = 82.7 +/- 18 years vs. on-pump = 82.2 +/- 2.2 years; p = NS) or in logistic EuroSCORE (off-pump = 11.2 +/- 12.3 vs. on-pump = 8.5 +/- 5.1; p = NS). However, the off-pump group had less complete revascularization (off-pump = 43.1% vs. on-pump = 83.3%, p = 0.0001) and shorter mean hospital stay (off-pump = 9.3 +/- 5.4 days vs. on-pump = 11.5 +/- 7.3 days; p = 0.09). Both groups showed low hospital mortality (off-pump = 1.5% vs. on-pump = 2.8%, p = NS). At 6-year follow-up, off-pump surgery patients had the same late prognosis (total survival: off-pump = 80% vs. on-pump = 77.4%, p = NS; cardiovascular mortality: off-pump = 15% vs. on-pump = 16.1%, p = NS). CONCLUSION: In octogenarians coronary artery bypass grafting had excellent results. The off-pump technique, even though it can mean less complete revascularization, leads to shorter hospital stay and has the same 6-year results as in patients operated under cardiopulmonary bypass.

Gene-gene interaction affects coronary artery disease risk.

INTRODUCTION: Various studies have compared coronary artery disease (CAD) patients with controls in order to determine which polymorphisms are associated with a higher risk of disease. The results have often been contradictory. Moreover, these studies evaluated polymorphisms in isolation and not in association, which is the way they occur in nature. OBJECTIVE: Our purpose was to evaluate the risk of CAD in patients with associated polymorphisms in the same gene or in differen genes. METHODS: We evaluated the risk associated with ACE DD, ACE 8 CC, ACT 174MM, AGT 235TT, MTHFR 677TT, MTHFR 1298AA, PON1 192RR and PON1 55MM in 298 CAD patients and 298 healthy individuals. We then evaluated the risk of associated polymorphisms in the same gene (ACE DD + ACE 8GG; AGT 174MM + AGT 235TT; MTHFR 677TT + MTHFR 1298AA). Finally, for the isolated polymorphisms which were significant, we evaluated the risk of polymorphism associations at different functional levels (ACE + AGT; ACE + MTHFR; ACE + PON1). Multiple logistic regression was used to identify independent risk factors for CAD. RESULTS: Isolated polymorphisms including ACE DD(p < 0.0001), ACE 8 gg (p=0.023), and MTHFR 1298AA (p = 0.049) presented with a significantly higher frequency in the CAD group. An association of polymorphisms in the same gene did not have an additive or synergistic effect, nor did it increase the risk of CAD. Polymorphic associations in different genes increased the risk of CAD, compared with the isolated polymorphisms. The association of ACE DD or ACE 8 GG with PON1 192RR increased the risk of CA fourfold (1.8 to 4.2). After logistic regression analysis, current smoking, family history, fibrinogen, diabetes, and the ACE DD or ACE 8 GG + MTHFR 1298AA and ACE DD or ACE 8 GG + PON1 192RR associations remained in the, model and proved to be independent predictors of CAD. CONCLUSIONS: The association of polymorphisms in the same gene did not increase the risk of the isolated polymorphism. The association of polymorphisms in genes belonging to different enzyme systems was always linked to increased risk compared to the isolated polymorphisms. This study may contribute to a better understanding of overall genetic risk for CAD rather than that associated with each polymorphism in isolation.

Clinical and angiographic profile of the diabetic patient: one-year follow-up.

UNLABELLED: Diabetes mellitus is associated with significant cardiovascular morbidity and mortality. The authors describe the clinical and angiographic profile of a diabetic population undergoing percutaneous coronary intervention, with one-year follow-up. METHODS: We retrospectively studied 769 patients (241 diabetic [D] and 528 nondiabetic [ND]) in terms of clinical and demographic characteristics, angiography and angioplasty data, and medical therapy, and analyzed the composite endpoint of adverse cardiac events at one month and one year. RESULTS: Women, older mean age, hypertension, dyslipidemia, previous stroke and renal insufficiency were more prevalent in the D group. It also had more patients with left ventricular dysfunction, multivessel disease and complex coronary lesions. A significantly higher number of stents per patient and more drug-eluting stents were implanted in this group. Occurrence of the composite endpoint at one-year follow-up was significantly higher in diabetic patients (D = 23.6% vs. ND = 15.9%; p = 0.012), and one-year total mortality was 5.8% in the D group vs. 2.3% in the ND group (p = 0.012). CONCLUSION: Even with aggressive percutaneous and pharmacological management, diabetes mellitus still has an adverse long-term prognosis.

Acute myocardial infarction after thrombolytic treatment of acute ischemic stroke.

Thrombolytic treatment in patients with acute ischemic stroke improves their clinical prognosis when administered within three hours of symptom onset. We report the case of a 57-year-old patient with a history of paroxysmal atrial fibrillation and hypertension who developed an anterior acute myocardial infarction after systemic thrombolytic treatment for acute ischemic stroke. Embolization of a pre-existing cardiac thrombus or in situ formation of a thrombus in a coronary artery has to be considered as a potential adverse effect of thrombolytic therapy in stroke patients.

Transient cardiomyopathy secondary to carbon monoxide poisoning.

A 4-year-old boy was found unconscious due to carbon monoxide poisoning, and required cardiopulmonary resuscitation, mechanical ventilation and inotropic support. Examination revealed cerebral edema, myocardial injury with left ventricular dilatation, depressed contractility and positive biomarkers. Complete recovery was seen at 4-month follow-up.

Human paraoxonase gene polymorphisms and coronary artery disease risk.

BACKGROUND: Complex diseases such as coronary artery disease (CAD), hypertension and diabetes are usually caused by individual susceptibility to multiple genes, environmental factors, and the interaction between them. The paraoxonase 1 (PON1) enzyme has been implicated in the pathogenesis of atherosclerosis and CAD. Two common polymorphisms in the coding region of the PON1 gene, which lead to a glutamine (Q)/arginine (R) substitution at position 192 and a leucine (L)/methionine (M) substitution at position 55, influence PON1 activity. Studies have investigated the association between these polymorphisms and CAD, but with conflicting results. AIMS: 1) To evaluate the association between PON1 polymorphisms and CAD risk; and 2) to study the interaction between PON1 polymorphisms and others in different candidate genes. METHODS: We evaluated the risk of CAD associated with PON1 Q192R and L55M polymorphisms in 298 CAD patients and 298 healthy individuals. We then evaluated the risk associated with the interaction of the PON1 polymorphisms with ACE DD, ACE 8 GG and MTHFR 1298AA. Finally, using a logistic regression model, we evaluated which variables (genetic, biochemical and environmental) were linked significantly and independently with CAD. RESULTS: We found that the PON1 55MM genotype was more common in the CAD population, but this did not reach statistical significance as a risk factor for CAD, while PON1 192RR presented an 80% higher relative risk compared to the population without this polymorphism. The interaction between PON1 192RR and MTHFR 1298AA, sited in different genes, increased the risk for CAD, compared with the polymorphisms in isolation (OR=2.76; 95% CI=1.20-6.47; p=0.009), as did the association of PON1 192RR with ACE DD, which presented a 337% higher risk compared to the population without this polymorphic association (OR=4.37; 95% CI=1.47-13.87; p=0.002). Similarly, the association between PON1 192RR and ACE 8 GG was linked to an even higher risk (OR=6.23; 95% CI=1.67-27.37; p<0.001). After logistic regression, smoking, family history, fibrinogen, diabetes, Lp(a) and the association of PON1 192RR + ACE 8 GG remained in the regression model and proved to be significant and independent risk factors for CAD. In the regression model the latter association had OR=14.113; p=0.018. CONCLUSION: When analyzed separately, the PON1 192RR genotype presented a relative risk for CAD 80% higher than in the population without this genotype. Its association with other genetic polymorphisms sited in different genes, coding for different enzymes and belonging to different physiological systems, always increased the risk for CAD. After correction for other conventional and biochemical risk factors, the PON1 192RR + ACE 8 GG association remained a significant and independent risk factor for CAD.