Associations of glycemic measures in the normal range with all-cause mortality in the absence of traditional risk factors.

CONTEXT: The investigation of the association between blood glucose within normal range and all-cause mortality among individuals without traditional risk factors is limited. OBJECTIVE: To determine the associations of 3 glycemic measures (fasting plasma glucose [FPG], hemoglobin A1c [HbA1c], and 2-h glucose) in the normal range with all-cause mortality among individuals without traditional risk factors. DESIGN: Retrospective cohort study. SETTING: US National Health and Nutrition Examination Survey in 1988-1994 and 1999-2018. PARTICIPANTS: Non-pregnant adults who had a measurement of 2-h glucose, FPG, and HbA1c, and absence of traditional risk factors were included. MAIN OUTCOME MEASURES: Cox proportional hazard models were performed to examine the associations of normal FPG (n=5793), normal HbA1c (n=8179), and normal 2-h glucose (n=3404) with all-cause mortality. RESULTS: The significant association was found between 2-h glucose within the normal range and all-cause mortality among those without traditional risk factors. Compared to participants with 2-h glucose <80 mg/dL, participants with a higher normal 2-h glucose level had a higher risk of all-cause mortality (110-139 mg/dL: HR, 1.80 [95% CI, 1.03-3.15]). In the subgroup analysis, significant associations were also found among people aged ≥60 years and men. No significant associations were found between normal FPG and HbA1c levels and all-cause mortality. CONCLUSIONS: Among US adults without traditional risk factors, high normal 2-h glucose level was positively associated with all-cause mortality. This result highlights the potential importance of maintaining a lower normal level of 2-h glucose for preventing mortality in individuals who are conventionally considered to be cardiovascular healthy.

Evaluation of Cardiovascular Risk Factors and Their Association With Coronary Artery Disease in Pakistani Adults.

BACKGROUND: Cardiovascular diseases (CVDs), especially coronary artery disease (CAD), are a major health burden, and their incidence is rising in countries like Pakistan. OBJECTIVE: The objective of this research was to assess the prevalence and association of cardiovascular risk factors with CAD in Pakistani adults. METHODOLOGY: The research was carried out from January 2023 to December 2023 at the Pakistan Institute of Medical Sciences (PIMS) Islamabad and Shifa International Hospital Islamabad, Pakistan, using a cross-sectional design. Based on predefined criteria, 320 individuals who were Pakistani nationals and over the age of 18 years old were included. Those having a history of congenital heart disease, pregnancy, significant comorbidities, coronary artery bypass grafting (CABG), or percutaneous coronary intervention (PCI) were excluded. Medical, lifestyle, and demographic data were collected, and clinical evaluations were carried out by qualified healthcare workers. The data was analyzed using descriptive statistics and relevant statistical tests. A p<0.05 was statistically significant. RESULTS: The study investigated cardiovascular risk factors and demographic traits in 320 adult Pakistanis. The majority of participants (n=181; 56.56%) were male and aged between 18 and 45. University education was predominant (n=170; 53.13%). Specifically, 147 participants (45.94%) had dyslipidemia, 74 (23.12%) had diabetes mellitus, and 112 (35.0%) had hypertension. Diabetes mellitus (OR: 9.60, 95% CI: 4.52-20.38, p<0.001), dyslipidemia (OR: 1.88, 95% CI: 1.29-2.75, p=0.001), and hypertension (OR: 2.67, 95% CI: 1.72-4.15, p<0.001) showed significant correlations with CAD. Poor socioeconomic status (OR: 3.00, 95% CI: 1.31-6.89, p=0.009) and genetic propensity (OR: 2.00, 95% CI: 1.02-3.92, p=0.040) were also significantly associated with CAD. CONCLUSION: Our study highlights diabetes as strongly linked to CAD in Pakistani adults, while socioeconomic status emerges as a significant predictor.

The Prevalence and Factors Associated with Coronary Heart Disease in Patients with Gout.

Gout is associated with increased risk of cardiovascular disease (CVD) morbidity and mortality. Therefore, an association between coronary heart disease (CHD) and gout deserves careful examination. AIM: . The aim of this study was to determine the prevalence of CHD and factors associated with CHD in patients (pts) with gout. MATERIALS AND METHODS: . The study involved 286 male patients with gout, age 51.2 [42.8; 59.4] years (ys), disease duration 6.2 [3.8; 12.1] ys. All patients underwent standard clinical examination screening traditional risk factors (TRFs) of CVDs. We estimated the adjusted odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: . CHD was found in 111 out of the 286 pts (38.8%), MI had a history in 29.7%. Compared to individuals with CHD, participants without CHD were older (56.7[52.1; 61.1] vs 46.2[40.6; 53.4] ys), had longer duration of gout (9.3[4.7; 15.1] vs 5.6[3.3; 9.7] ys) (for all p < 0.05). Abdominal obesity (OR, 3.6; 95% CI, 1.2-10.9), family history of CHD (OR, 2.2; 95% CI, 1.3-3.7), disease duration of gout more 10 ys (OR, 2.8; 95% CI, 1.6-4.7), age of gout onset < 35 ys (OR, 5.5; 95% CI, 2.6-11.7), intraosseous tophi (OR, 3.03; 95% CI, 1.8-5.01), nephrolithiasis (OR, 1.7; 95% CI, 1.04-3.04), renal failure (OR, 5.6; 95% CI, 2.7-11.4), serum total cholesterol (TC), (OR, 1.6; 95% CI, 1.0-2.8), serum creatinine (OR, 2.5; 95% CI, 1.2-5.1), increased the risk for CHD in patients with a gout. CONCLUSIONS: . The prevalence of CHD was 38.8% among individuals with gout (one-third of patients had a history of MI 29.7%). Our study showed that both TRFs of CVD and the severity of gout and a history of renal failure contribute to the development of CHD in patients with gout.

[Subclinical atherosclerosis of the carotid arteries in patients with rheumatoid arthritis with low cardiovascular risk].

AIM: To evaluate the detection rate of subclinical carotid atherosclerosis in rheumatoid arthritis (RA) patients with low cardiovascular risk (CVR). MATERIALS AND METHODS: The study included 182 RA patients with low CVR (mSCORE<1%) and no established cardiovascular diseases and a control group comprising 100 people. Atherosclerotic lesion of the carotid arteries was assessed using Doppler ultrasound of the carotid arteries and was determined by the detection of atherosclerotic plaque (ASP) - the local increase in the thickness of the intima-media complex (IMT) >1.5 mm. RESULTS: Carotid ASP were observed more frequently in RA patients with low CVR than in the control group (17% versus 8%; p=0.02). The frequency of ASP in RA patients with low CVR did not depend on the disease's stage or activity and ongoing therapy. In RA, the detection of subclinical atherosclerosis was associated with traditional risk factors: carotid ASP were detected 4 times more often in men than in women (48% versus 12%, p<0.01); carotid IMT correlated with age (R=0.46), body mass index (R=0.17), LDL-C level (R=0.20), systolic blood pressure (R=0.17); p<0.05 in all cases. According to a multivariate model, in RA, the risk of developing ASP increased in the presence of dyslipidemia (odds ratio - OR 2.97; 95% confidence interval - CI 1.36-6.49; p=0.006) and arterial hypertension (OR 2.16; 95% CI 1.03-4.54; p=0.04). In RA patients with carotid ASP, sCD40L level was associated with carotid IMT (R=0.32; p=0.04) and cholesterol concentration (R=0.39; p=0.01). CONCLUSION: Subclinical atherosclerotic lesions of the carotid arteries were observed in 24% of RA patients with low cardiovascular risk and were detected almost 2 times more often than in the control group. In RA patients with low CVR, the risk of developing carotid ASP increased by 2-3 times with concomitant hypertension and dyslipidemia. The carotid IMT was associated with traditional risk factors - age, gender, lipid levels and blood pressure indicators, in cases of detection of ASP - with an immunoinflammatory marker - sCD40L.

Comorbidities and clinical symptoms can modify myocardial function: a cross-sectional study with PET/CT / Comorbilidades y síntomas clínicos que pueden modificar la función miocárdica: estudio transversal con PET/TC

Abstract Objective: Associating comorbidities and cardiac symptoms that alter myocardial mechanical function could help clinicians to correctly identify at-risk population. Methods: We conducted a functional open population cross-sectional study of patients referred to a positron emission tomography/computed tomography unit in Mexico City for evaluation of myocardial function, perfusion, and coronary circulation. Ischemia was defined as a sum difference score ≥ 2. Association between comorbidities and cardiac symptoms was tested using logistic regression models and trend analysis. We performed an interaction analysis to evaluate the addition of any accompanying symptoms to comorbid conditions on impairment of myocardial function. Results: One thousand two hundred and seventy-three patients were enrolled, 66.1% male, with a mean age of 62.4 (± 12.7) years, 360 (28.7%) with ischemia, 925 (72.7%) with at least one comorbidity, and 676 (53.1%) had at least one associated cardiac symptom. Patients without ischemia, type 2 diabetes, arterial hypertension, and adverse cardiac symptoms were associated with adverse mechanical, perfusion, and coronary flow parameters. We observed a trend of a cumulative number of comorbidities and cardiac symptoms with increased ischemia and decreased coronary flow. Only in decreased left ventricular ejection fraction, we demonstrated an interaction effect between increased comorbidities and adverse symptoms. Conclusion: The high burden of comorbidities and symptoms in our population alters myocardial function regardless of the level of ischemia.

Resumen Objetivo: La asociación de comorbilidades y síntomas cardíacos que alteran la función miocárdica podría ayudar a los médicos a identificar correctamente a poblaciones de riesgo. Métodos: Se realizó un estudio transversal en población abierta de pacientes referidos a una unidad de PET/CT en la Ciudad de México para evaluación de la función miocárdica, perfusión y circulación coronaria. La isquemia se definió como una suma de diferencia de puntuación (SDS) ≥ 2. La asociación entre las comorbilidades y los síntomas cardíacos se fundamentó mediante modelos de regresión logística y análisis de tendencias. Realizamos un análisis de interacción para evaluar la adición de cualquier síntoma acompañante a condiciones comórbidas en el deterioro de la función miocárdica. Resultados: Se incluyeron 1.273 pacientes, 66,1% del sexo masculino, con una edad media de 62,4 (± 12.7) años, 360 (28,7%) con isquemia, 925 (72,7%) con al menos una comorbilidad y 676 (53,1%) con al menos una menos un síntoma cardíaco asociado. En pacientes sin isquemia, la diabetes mellitus tipo 2, la hipertensión arterial y los síntomas cardíacos adversos se asociaron con parámetros mecánicos, de perfusión y de flujo coronario adversos. Se observó una tendencia con el número acumulado de comorbilidades y síntomas cardíacos con aumento de la isquemia y disminución del flujo coronario. Solo en la disminución de la FEVI se demostró un efecto de interacción entre el aumento de las comorbilidades y los síntomas adversos. Conclusión: La alta carga de comorbilidades y síntomas en nuestra población altera la función miocárdica independientemente del nivel de isquemia.

Prevalence of Traditional Risk Factors in First-Degree Relatives of Patients With Established Cardiovascular Disease.

INTRODUCTION: World Health Organization (WHO)/International Society of Hypertension (ISH) risk prediction charts are useful for predicting 10-year combined myocardial infarction and stroke risk (fatal and non-fatal). Hence the current study was conducted to assess the 10-year risk of cardiovascular disease among adults in Ahmedabad, India. AIMS: The primary aim of the study was to assess the cardiovascular risk among first-degree relatives of patients attending the outpatient clinic. Also, to create awareness regarding assessment of cardiovascular risk among the studied group. METHODS AND MATERIALS: A cross-sectional study was carried out among 372 first-degree relatives of patients at an out-patient cardiology clinic present in Vadaj, Ahmedabad. The WHO/ISH risk prediction chart for South-East Asia Region D (SEAR D) was used for calculating the 10-year cardiovascular risk. RESULTS: A maximum (80.10%) of the study participants were in the low-risk (<10%) category followed by 8.33% for moderate-risk (10-20%), 7.25% for moderately high-risk (20-30%), 2.42% for high-risk (30-40%) and 1.88% for very high-risk (>40%). CONCLUSION: WHO/ISH risk prediction charts provide a quick and effective way to assess and categorize the population in a low-resource setting which in turn helps in delivering focused intervention to the high-risk groups.

Precipitating factors in patients with spontaneous coronary artery dissection: Clinical, laboratoristic and prognostic implications.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) often presents with acute coronary syndrome and underlying pathophysiology involves the interplay between predisposing factors and precipitating stressors, such as emotional and physical triggers. In our study we sought to compare clinical, angiographic and prognostic features in a cohort of patients with SCAD according to the presence and type of precipitating stressors. METHODS: Consecutive patients with angiographic evidence of SCAD were divided into three groups: patients with emotional stressors, patients with physical stressors and those without any stressor. Clinical, laboratoristic and angiographic features were collected for each patient. The incidence of major adverse cardiovascular events, recurrent SCAD and recurrent angina was assessed at follow-up. RESULTS: Among the total population (64 subjects), 41 [64.0%] patients presented with precipitating stressors, including emotional triggers (31 [48.4%] subjects) and physical efforts (10 [15.6%] subjects). As compared with the other groups, patients with emotional triggers were more frequently female (p = 0.009), had a lower prevalence of hypertension (p = 0.039] and dyslipidemia (p = 0.039), were more likely to suffer from chronic stress (p = 0.022) and presented with higher levels of C-reactive protein (p = 0.037) and circulating eosinophils cells (p = 0.012). At a median follow-up of 21 [7; 44] months, patients with emotional stressors experienced higher prevalence of recurrent angina (p = 0.025), as compared to the other groups. CONCLUSIONS: Our study shows that emotional stressors leading to SCAD may identify a SCAD subtype with specific features and a trend towards a worse clinical outcome.

Coronary Artery Disease Risk Prediction in Young Adults: How Can We Overcome the Dominant Effect of Age?

PURPOSE OF REVIEW: We review the limitations of current approaches for predicting Coronary Artery Disease (CAD) in young adults and explore the alternative approaches identify high-risk individuals in this population. RECENT FINDINGS: Atherosclerosis begins in childhood, and young individuals with genetic predisposition and individuals with early exposure to traditional and non-traditional risk factors have an increased lifetime risk of CAD. However, most risk prediction models have been developed and validated in middle and older age groups and focus on short-term risk. Therefore, alternative approaches are needed in younger individuals. Genetic scores, biomarkers, imaging studies, and multi-omics data all have the potential to be used and help identify high-risk individuals.

Impact of genetic information on coronary disease risk in Madeira: The GENEMACOR study.

INTRODUCTION: Coronary artery disease (CAD), characterized by an atherogenic process in the coronary arteries, is one of the leading causes of death in Madeira. The GENEMACOR (GENEs in MAdeira and CORonary Disease) study sought to investigate the main risk factors - environmental and genetic - and estimate whether a genetic risk score (GRS) improves CAD prediction, discrimination and reclassification. METHODS: Traditional risk factors and 33 CAD genetic variants were considered in a case-control study with 3139 individuals (1723 patients and 1416 controls). The multivariate analysis assessed the likelihood of CAD. A multiplicative GRS (mGRS) was created, and two models (with and without mGRS) were prepared. Two areas under receiver operating characteristic curve (area under curve (AUC)) were analyzed and compared to discriminate CAD likelihood. Net reclassification improvement (NRI) and integrated discrimination index (IDI) were used to reclassify the population. RESULTS: All traditional risk factors were strong and independent predictors of CAD, with smoking being the most significant (OR 3.25; p<0.0001). LPA rs3798220 showed a higher CAD likelihood (odds ratio 1.45; p<0.0001). Individuals in the fourth mGRS quartile had an increased CAD probability of 136% (p<0.0001). A traditional risk factor-based model estimated an AUC of 0.73, rising to 0.75 after mGRS inclusion (p<0.0001), revealing a better fit. Continuous NRI better reclassified 28.1% of the population, and categorical NRI mainly improved the reclassification of the intermediate risk group. CONCLUSIONS: CAD likelihood was influenced by traditional risk factors and genetic variants. Incorporating GRS into the traditional model improved CAD predictive capacity, discrimination and reclassification. These approaches may provide helpful diagnostic and therapeutic advances, especially in the intermediate risk group.

Comorbidities and cardiac symptoms can modify myocardial function regardless of ischemia: a cross-sectional study with PET/CT.

Objective: Associating comorbidities and cardiac symptoms that alter myocardial mechanical function could help clinicians to correctly identify at-risk population. Methods: We conducted a functional open population cross-sectional study of patients referred to a positron emission computed tomography/computed tomography unit in Mexico City for evaluation of myocardial function, perfusion, and coronary circulation. Ischemia was defined as a sum difference score (SDS) > 2. Association between comorbidities and cardiac symptoms was tested using logistic regression models and trend analysis. We performed an interaction analysis to evaluate the addition of any accompanying symptoms to comorbid conditions on impairment of myocardial function. Results: One thousand two hundred and seventy-three patients were enrolled, 66.1% male, with a mean age of 62.4 (± 12.7) years, 360 (28.7%) with ischemia, 925 (72.7%) with at least one comorbidity, and 676 (53.1%) had at least one associated cardiac symptom. Patients without ischemia, type 2 diabetes, arterial hypertension, and adverse cardiac symptoms were associated with adverse function, perfusion, and coronary flow parameters. We observed a trend of a cumulative number of comorbidities and cardiac symptoms with increased ischemia and decreased coronary flow. Only in decreased LVEF, we demonstrated an interaction effect between increased comorbidities and adverse symptoms. Conclusions: The high burden of comorbidities and symptoms in our population alter myocardial function regardless of the level of ischemia.

A review of the risk and precipitating factors for spontaneous coronary artery dissection.

Introduction: Spontaneous coronary artery dissection (SCAD) accounts for 1%-4% of cases of acute coronary syndrome (ACS). SCAD is caused by separation occurring within or between any of the three tunics of the coronary artery wall. This leads to intramural hematoma and/or formation of false lumen in the artery, which leads to ischemic changes or infarction of the myocardium. The incidence of SCAD is higher in women than in men, with a ratio of approximately 9:1. It is estimated that SCAD is responsible for 35% of ACS cases in women under the age of 60. The high frequency is particularly observed during pregnancy and in the peripartum period (first week). Traditional risk factors are rare in patients with SCAD, except for hypertension. Patients diagnosed with SCAD have different combinations of risk factors compared with patients who have atherosclerotic changes in their coronary arteries. We presented the most common so-called "non-traditional" risk factors associated with SCAD patients. Risk factors and precipitating disorders which are associated with SCAD: In the literature, there are few diseases frequently associated with SCAD, and they are identified as predisposing factors. The predominant cause is fibromuscular dysplasia, followed by inherited connective tissue disorders, systemic inflammatory diseases, pregnancy, use of sex hormones or steroids, use of cocaine or amphetamines, thyroid disorders, migraine, and tinnitus. In recent years, the genetic predisposition for SCAD is also recognized as a predisposing factor. The precipitating factors are also different in women (emotional stress) compared with those in men (physical stress). Women experiencing SCAD frequently describe symptoms of anxiety and depression. These conditions could increase shear stress on the arterial wall and dissection of the coronary artery wall. Despite the advancement of SCAD, we can find significant differences in the clinical presentation between women and men. Conclusion: When evaluating patients with chest pain or other ACS symptoms who have a low cardiovascular risk, particularly female patients, it is important to consider the possibility of ACS due to SCAD, particularly in conditions often associated with SCAD. This will increase the recognition of SCAD and the timely treatment of affected patients.

Essential Thrombocytosis in Patients <40 Years Old With Acute Coronary Syndromes: A Not So Uncommon Underlying Diagnosis Often Overlooked.

BACKGROUND: In patients under <40 years, traditional cardiovascular (CV)-risk factors are a less likely cause of acute coronary syndromes (ACS) compared to older counterparts. AIMS: To estimate the prevalence of essential thrombocytosis (ET), a hematological disorder and less-prevalent risk factor, in young patients presenting with ACS. METHODS: We constructed a retrospective database of all patients <40 years (n=271) that had consecutively undergone coronary angiography (CAG) after their first ACS within our hospital within the last ten years (2010-2020) and had known thrombocyte counts (n=241). Patients with thrombocytes >450x10*9/L were screened for this hematological disorder. RESULTS: In our database, we identified 15 subjects with thrombocytosis. One was previously known as ET. Of the remaining 14 patients, five were considered reactive/secondary thrombocytosis, and four were lost to follow-up, four were eventually diagnosed with ET, one remains uncertain. The diagnosis was newly established before the initiation of this study in two patients (average delay: six years). Two patients were identified as a result of this study.  Conclusion: With a prevalence of at least 2.1%, ET appears not uncommon in patients <40 years with ACS. Moreover, screening patients with ACS and elevated thrombocytes yielded a novel diagnosis of ET in 27% of patients. The diagnosis was initially missed in all cases. Since the timing of revascularization should be adjusted to thrombocyte count/initiation of ET therapy to prevent thrombotic complications, cardiologists should know, recognize and screen for this pathology in ACS-patients, notably in those with absent traditional CV-risk factors: an 'ACS-protocol' aimed at less-prevalent risk factors could support this.

A Less than Provocative Approach for the Primary Prevention of CAD.

Coronary artery disease (CAD) risk increases in proportion to the magnitude and duration of exposure to plasma low-density lipoprotein cholesterol (LDL-C), doubling every additional decade of exposure. Early primary prevention is three times more effective than initiated later. Several clinical trials show plasma LDL-C of 15-40 mg/dL is more effective and equally safe as the Current Cardiovascular Clinical Practice Guidelines (CCCPG) recommended target of 70mg/dL. The cholesterol in the blood is the excess synthesized by the cells and secreted into the blood for disposal in the liver. The CCCPG is inadequate since traditional risk factors (TRF) are not detectable until the sixth and seventh decade. The genetic risk score (GRS) evaluated in 1 million individuals as a risk stratifier for CAD is superior to TRF. Genetic risk for CAD was reduced by 30-50% by statin therapy, PCSK9 inhibitors, and lifestyle changes. The GRS does not change during one's lifetime and is inexpensive. Incorporating genetic risk stratification into CCCPG would induce a paradigm shift in the primary prevention of CAD.

Traditional risk factors and cancer-related factors associated with cardiovascular disease risk in head and neck cancer patients.

Background: Risk of incident cardiovascular disease (CVD) in head and neck squamous cell carcinoma (HNSCC) patients is under-reported. We assessed the association of HNSCC-related factors and traditional risk factors with 1- and 5-year CVD risk in HNSCC patients without prevalent CVD at cancer diagnosis. Methods: A clinical cohort of 1,829 HNSCC patients diagnosed between 2012 and 2018, at a National Cancer Institute (NCI)-designated cancer center was included. Information on HNSCC-related factors [HNSCC anatomical subsite, stage at diagnosis, treatment, and tumor human papillomavirus (HPV) status] were extracted from the tumor registry. Data on traditional risk factors (hypertension, dyslipidemia, diabetes, tobacco smoking status, and obesity) were extracted from the electronic health records system (EHR) at baseline (HNSCC diagnosis). A composite of ischemic heart disease, heart failure, and ischemic stroke was the outcome of interest in time to event analysis. Hazard ratio (HR) (95% CI) were reported with death as a competing risk. Results: In patients diagnosed with HNSCC, 10.61% developed incident CVD events by 1-year post cancer diagnosis. One-year CVD risk was lower in patients using antihypertensive medications at baseline, compared to patients without baseline hypertension [HR (95% CI): 0.41 (0.24-0.61)]. One-year CVD risk was high in patients receiving HNSCC surgery. Patients receiving radiation therapy had a higher 5-year CVD risk than surgery patients [HR (95% CI): 2.17 (1.31-3.04)]. Patients using antihypertensive medications had a lower 5-year CVD risk than patients without baseline hypertension [HR (95% CI): 0.45 (0.22-0.75)]. Older age and diabetes were associated with increased 1- and 5-year CVD risk. HPV-negative patients were older (p 0.006) and had a higher 5-year cumulative incidence of CVD (p 0.013) than HPV-positive patients. Conclusion: Traditional risk factors and cancer-related factors are associated with CVD risk in HNSCC patients. Future research should investigate the role of antihypertensive medications in reducing CVD risk in HNSCC patients.

Accelerated atherosclerosis and cardiovascular disease in systemic lupus erythematosus / Aterosclerosis acelerada y enfermedad cardiovascular en el lupus eritematoso sistémico

ABSTRACT Cardiovascular disease (CVD), particularly coronary heart disease and stroke, is one of the most important causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). The increased prevalence of CVD and subclinical atherosclerosis, even after adjustment for traditional risk factors, are well established. Several associations with disease-related clinical, genetic and immunological features have been identified. The SLE-specific stratification algorithms with emphasis on composite risk-assessment scores including both traditional risk factors and novel biomarkers is recommended. The clinical complexity of accelerated atherosclerosis will most likely require an integrated approach for the identification, treatment, and intensive study into this aspect of SLE that will ultimately lead to improved cardiovascular outcomes for these patients.

RESUMEN La enfermedad cardiovascular (ECV), en particular la enfermedad coronaria y el ictus, es una de las causas más importantes de morbimortalidad en pacientes con lupus eritematoso sistémico (LES). El aumento en la prevalencia de la ECV y de la aterosclerosis subclínica, aun después del ajuste de los factores de riesgo tradicionales, está claramente establecida. Se han identificado diversas asociaciones con características clínicas, genéticas e inmunológicas relacionadas con la enfermedad. Se recomienda el uso de los algoritmos de estratificación específicos para el LES, con énfasis en los puntajes compuestos de evaluación de riesgo, incluyendo tanto los factores de riesgo tradicionales como los nuevos biomarcadores. La complejidad clínica de la aterosclerosis acelerada muy probablemente requerirá un abordaje integral para la identificación, el tratamiento y el estudio intensivo de este aspecto del LES, que en última instancia permita obtener mejores desenlaces cardiovasculares en estos pacientes.

Ischemic Heart Disease and Rheumatoid Arthritis-Two Conditions, the Same Background.

Rheumatoid arthritis (RA) is one of the most frequent inflammatory rheumatic diseases, having a considerably increased prevalence of mortality and morbidity due to cardiovascular disease (CVD). RA patients have an augmented risk for ischemic and non-ischemic heart disease. Increased cardiovascular (CV) risk is related to disease activity and chronic inflammation. Traditional risk factors and RA-related characteristics participate in vascular involvement, inducing subclinical changes in coronary microcirculation. RA is considered an independent risk factor for coronary artery disease (CAD). Endothelial dysfunction is a precocious marker of atherosclerosis (ATS). Pro-inflammatory cytokines (such as TNFα, IL-1, and IL-6) play an important role in synovial inflammation and ATS progression. Therefore, targeting inflammation is essential to controlling RA and preventing CVD. Present guidelines emphasize the importance of disease control, but studies show that RA- treatment has a different influence on CV risk. Based on the excessive risk for CV events in RA, permanent evaluation of CVD in these patients is critical. CVD risk calculators, designed for the general population, do not use RA-related predictive determinants; also, new scores that take into account RA-derived factors have restricted validity, with none of them encompassing imaging modalities or specific biomarkers involved in RA activity.

Framing Cause-Effect Relationship of Acute Coronary Syndrome in Patients with Chronic Kidney Disease.

The main causes of death in patients with chronic kidney disease (CKD) are of cardiovascular nature. The interaction between traditional cardiovascular risk factors (CVRF) and non-traditional risk factors (RF) triggers various complex pathophysiological mechanisms that will lead to accelerated atherosclerosis in the context of decreased renal function. In terms of mortality, CKD should be considered equivalent to ischemic coronary artery disease (CAD) and properly monitored. Vascular calcification, endothelial dysfunction, oxidative stress, anemia, and inflammatory syndrome represents the main uremic RF triggered by accumulation of the uremic toxins in CKD subjects. Proteinuria that appears due to kidney function decline may initiate an inflammatory status and alteration of the coagulation-fibrinolysis systems, favorizing acute coronary syndromes (ACS) occurrence. All these factors represent potential targets for future therapy that may improve CKD patient's survival and prevention of CV events. Once installed, the CAD in CKD population is associated with negative outcome and increased mortality rate, that is the reason why discovering the complex pathophysiological connections between the two conditions and a proper control of the uremic RF are crucial and may represent the solutions for influencing the prognostic. Exclusion of CKD subjects from the important trials dealing with ACS and improper use of the therapeutical options because of the declined kidney functioned are issues that need to be surpassed. New ongoing trials with CKD subjects and platelets reactivity studies offers new perspectives for a better clinical approach and the expected results will clarify many aspects.

Thromboembolic and atherosclerotic cardiovascular events in inflammatory bowel disease: epidemiology, pathogenesis and clinical management.

Inflammatory bowel disease (IBD) is associated with an increased risk of cardiovascular disease (CVD). The increased risk of CVD concerns an increased risk of venous thromboembolism (VTE), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), at corresponding relative risks of 2.5, 1.2 and 2.0, respectively, as compared with the general population. Especially young patients under the age of 40 years run a relatively high risk of these complications when compared with the general population. Chronic systemic inflammation causes a hypercoagulable state leading to the prothrombotic tendency characteristic of VTE, and accelerates all stages involved during atherogenesis in ASCVD. Increased awareness of VTE risk is warranted in patients with extensive colonic disease in both ulcerative colitis and Crohn's disease, as well as during hospitalization, especially when patients are scheduled for surgery. Similarly, critical periods for ASCVD events are the 3 months prior to and 3 months after an IBD-related hospital admission. The increased ASCVD risk is not fully explained by an increased prevalence of traditional risk factors and includes pro-atherogenc lipid profiles with high levels of small dense low-density lipoprotein cholesterol particles and dysfunctional high-density lipoprotein cholesterol. Risk factors associated with HF are location and extent of inflammation, female sex, and age exceeding 40 years. A dose-dependent increase of overall CVD risk has been reported for corticosteroids. Immunomodulating maintenance therapy might reduce CVD risk in IBD, not only by a direct reduction of chronic systemic inflammation but possibly also by a direct effect of IBD medication on platelet aggregation, endothelial function and lipid and glucose metabolism. More data are needed to define these effects accurately. Despite accumulating evidence on the increased CVD risk in IBD, congruent recommendations to develop preventive strategies are lacking. This literature review provides an overview of current knowledge and identifies gaps in evidence regarding CVD risk in IBD, by discussing epidemiology, pathogenesis, and clinical management.

Traditional risk factors and combined genetic markers of recurrent ischemic stroke in adults.

BACKGROUND: The involvement of traditional risk factors and combined genetic markers of recurrent arterial ischemic stroke (AIS) in adults remains unclear. OBJECTIVE: This study aims to determine significant clinical and genetic factors of AIS recurrence, and to investigate the combined effect of genotypes on the occurrence of a second cerebral ischemic attack. METHODS: We investigated a cohort study of AIS patients (18-50 years old) followed in the neurology department over 5 years. Traditional and genetic risk factors were carried through a multivariable logistic regression model. We used a Cox proportional hazard model for identifying predictors of recurrence. RESULTS: Two hundred and seventy patients were enrolled in our study. The risk of AIS recurrence was 36.2% within 5 years. The potential risk of recurrence of AIS increased with traditional and genetic risk factors such as hypertension, diabetes mellitus, heart failure, and family history of cerebrovascular diseases. This risk increased with increasing number of genetic factors. The hazard ratio (HR) was 0.66 (95% confidence interval [CI] 0.97-2.67) for the subject with one genetic factor, 1.61 (95% CI 0.97-2.25) for combined methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and 2.57 (95% CI 1.32-4.99) for combined factor V Leiden (FVL) and MTHFR polymorphisms (677 or 1298). The HR for the three polymorphisms combined was 6.04 (95% CI 2.40-15.16). CONCLUSIONS: Our findings suggest that cumulative effect of both traditional and common genetic risk factors was associated with recurrence of ischemic stroke. We demonstrated for the first time that a combined genotype FVL/MTHFR profile increase the risk of a second cerebral ischemic attack.

Prediction of HF-Related Mortality Risk Using Genetic Risk Score Alone and in Combination With Traditional Risk Factors.

Background: Common variants may contribute to the variation of prognosis of heart failure (HF) among individual patients, but no systematical analysis was conducted using transcriptomic and whole exome sequencing (WES) data. We aimed to construct a genetic risk score (GRS) and estimate its potential as a predictive tool for HF-related mortality risk alone and in combination with traditional risk factors (TRFs). Methods and Results: We reanalyzed the transcriptomic data of 177 failing hearts and 136 healthy donors. Differentially expressed genes (fold change >1.5 or <0.68 and adjusted P < 0.05) were selected for prognosis analysis using our whole exome sequencing and follow-up data with 998 HF patients. Statistically significant variants in these genes were prepared for GRS construction. Traditional risk variables were in combination with GRS for the construct of the composite risk score. Kaplan-Meier curves and receiver operating characteristic (ROC) analysis were used to assess the effect of GRS and the composite risk score on the prognosis of HF and discriminant power, respectively. We found 157 upregulated and 173 downregulated genes. In these genes, 31 variants that were associated with the prognosis of HF were finally identified to develop GRS. Compared with individuals with low risk score, patients with medium- and high-risk score showed 2.78 (95%CI = 1.82-4.24, P = 2 × 10-6) and 6.54 (95%CI = 4.42-9.71, P = 6 × 10-21) -fold mortality risk, respectively. The composite risk score combining GRS and TRF predicted mortality risk with an HR = 5.41 (95% CI = 2.72-10.64, P = 1 × 10-6) for medium vs. low risk and HR = 22.72 (95% CI = 11.9-43.48, P = 5 × 10-21) for high vs. low risk. The discriminant power of GRS is excellent with a C statistic of 0.739, which is comparable to that of TRF (C statistic = 0.791). The combination of GRS and TRF could significantly increase the predictive ability (C statistic = 0.853). Conclusions: The 31-SNP GRS could well distinguish those HF patients with poor prognosis from those with better prognosis and provide clinician with reference for the intensive therapy, especially when combined with TRF. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier: NCT03461107.