Quiet flames: inflammation without traditional risk factors.

Age-related Changes in Renal Arterio-Arteriolosclerosis in Kidney Disease: Renal Biopsy-based Study

Funding Acknowledgements Type of funding sources: None. Background Atherosclerosis is inherently an inflammatory process, with a complex interplay of inflammatory markers. It is established that these inflammatory markers play an important role in patients of Coronary Artery Disease(CAD) with traditional cardiovascular risk factors. However, the role of inflammation in the atherosclerotic process in patients of CAD without traditional risk factors is still not clearly known. Purpose Our purpose was to determine whether in patients of CAD without traditional risk factors, TLR4(Toll like receptor 4) expression as a marker of inflammation is similar to that in patients of CAD with traditional risk factors. Materials and Methods This observational cross sectional study was done between July’20 to Dec’21. Equal number of patients of CAD with and without traditional cardiovascular risk factors undergoing Coronary Artery Bypass Grafting (CABG) were enrolled. The risk factors considered were Hypertension, Diabetes, Dyslipidemia, Obesity and Addiction to Tobacco and/or Alcohol. A minimum of two punch biopsy samples of aortic tissue was taken from each subject undergoing CABG. Immunohistochemistry for TLR4, was done in Ventana BenchMark GX System. The primary TLR4 antibody was procured from reputed source. Results The presence or absence of TLR4 expression was associated significantly with the Syntax scores (37.40±4.74 vs 29.5±8.71; p value=0.036), total Cholesterol (187±35.06mg/dL vs 130±35.69 mg/dL ;p value 0.010) and LDL cholesterol (118.86±28.12mg/dL vs 64.21±25.61 mg/dL; p value 0.003). TLR4 expression, however, was not significantly associated with the number of coronary vessels involved (p=0.298). TLR4 expression was also not significantly associated with any other individual risk factors. However, when the traditional risk factors were considered in combination, TLR4 expression was associated significantly with the number of risk factors present(p=0.029) the strongest being in those having 4 traditional risk factors. The level of TLR4 expression gradually declined with the decrease in the number of risk factors, having mostly weak or negative expression in patients without any traditional risk factors. Conclusion Patients with CAD without any traditional risk factors, had a less severe coronary artery disease as manifested by lower Syntax scores, and had lower degree of TLR4 expression. Patients with CAD with traditional risk factors had more severe coronary artery disease as evidenced by higher Syntax scores, and had higher degree of TLR4 expression proportional to the number of traditional risk factors present. Thus, differential TLR4 expression in CAD patients with and without traditional risk factors indicated a difference in inflammatory state between the two groups and warrants further investigation.

Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort

With successful antiretroviral therapy, patients infected with the human immunodeficiency virus (HIV) are living longer; however, recent reports suggest increased rates of coronary heart disease (CHD) among HIV-infected patients,1 and cardiovascular disease has become an important cause of morbidity and mortality in this population.2 Increased CHD rates in the HIV population may relate to traditional risk factors, including advancing age, higher smoking rates, dyslipidemia, insulin resistance, and impaired glucose tolerance. Cardiovascular disease may also be due to nontraditional factors, including changes in body composition with loss of subcutaneous fat and/or accumulation of visceral fat in some patients, inflammation, and direct effects of the virus on the vasculature, as well as to direct effects of specific antiretroviral drugs. Important questions remain as to the pathogenesis, detection, and treatment of cardiovascular disease and related risk factors in HIV-infected patients. These questions concern, among other things, the design of adequate trials to determine CHD incidence and the utility of existing CHD guidelines for screening, prevention, treatment, and risk stratification. To ascertain the state of the science with respect to these and related questions, a multidisciplinary conference with interested HIV specialists, cardiologists, endocrinologists, primary care physicians, National Institutes of Health representatives, and patient advocates was convened June 28–30, 2007, in Chicago, Ill, and chaired by Drs Steven Grinspoon and Robert Eckel. The discussions focused on 6 areas of interest, each with its own working group, including the following: (1) the contribution of metabolic and anthropometric abnormalities to cardiovascular disease risk factors (chaired by Drs Carl Grunfeld and Donald Kotler); (2) the epidemiological evidence for cardiovascular disease and its relationship to highly active antiretroviral therapy (HAART; chaired by Drs Judy Currier and Jens Lundgren); (3) the effects of HIV infection and antiretroviral therapy on the heart and vasculature (chaired by Drs Michael Dube …

Are We There Yet? Pediatric Screening for Inflammatory Biomarkers and Low Cardiorespiratory Fitness to Identify Youth at Increased Risk of Cardiovascular Disease

Despite women having fewer traditional risk factors (eg, hypertension, diabetes), strokes are more common in women than men aged ≤45 years. This study examined the contributions of traditional and nontraditional risk factors (eg, migraine, thrombophilia) in the development of strokes among young adults. This retrospective case-control study used Colorado's All Payer Claims Database (2012-2019). We identified index stroke events in young adults (aged 18-55 years), matched 1:3 to stroke-free controls, by (1) sex, (2) age±2 years, (3) insurance type, and (4) prestroke period. All traditional and nontraditional risk factors were identified from enrollment until a stroke or proxy-stroke date (defined as the prestroke period). Conditional logistic regression models stratified by sex and age group first assessed the association of stroke with counts of risk factors by type and then computed their individual and aggregated population attributable risks. We included 2618 cases (52% women; 73.3% ischemic strokes) and 7827 controls. Each additional traditional and nontraditional risk factors were associated with an increased risk of stroke in all sex and age groups. In adults aged 18 to 34 years, more strokes were associated with nontraditional (population attributable risk: 31.4% men and 42.7% women) than traditional risk factors (25.3% men and 33.3% women). The contribution of nontraditional risk factors declined with age (19.4% men and 27.9% women aged 45-55 years). The contribution of traditional risk factors peaked among patients aged 35 to 44 years (32.8% men and 39.7% women). Hypertension was the most important traditional risk factor and increased in contribution with age (population attributable risk: 27.8% men and 26.7% women aged 45 to 55 years). Migraine was the most important nontraditional risk factor and decreased in contribution with age (population attributable risk: 20.1% men and 34.5% women aged 18-35 years). Nontraditional risk factors were as important as traditional risk factors in the development of strokes for both young men and women and have a stronger association with the development of strokes in adults younger than 35 years of age.

Highlights From the Circulation Family of Journals.

Usefulness of Brachial Artery Flow-Mediated Dilation to Predict Long-Term Cardiovascular Events in Subjects Without Heart Disease

BackgroundInflammation plays an important role in the pathogenesis of atherosclerosis. The link between rheumatoid arthritis (RA) and an increased risk of cardiovascular disease and mortality is well established; however, the association between inflammatory bowel disease (IBD) and cardiovascular risk is controversial. Arterial stiffness is both a marker and risk factor for atherosclerosis. Here we aimed to 1) compare circulating markers of inflammation and endothelial dysfunction, traditional cardiovascular risk factors, and arterial stiffness between RA and IBD to help to understand their different associations with cardiovascular disease; 2) assess the impacts of circulating markers of inflammation and endothelial dysfunction, and traditional risk factors on arterial stiffness.MethodsPatients with RA (n = 43) and IBD (n = 42), and control subjects (n = 73) were recruited. Plasma inflammatory markers and von Willebrand factor (vWF) were measured by Multiplex assays or ELISA. Arterial stiffness was determined by brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) was measured. Framingham Risk Score (FRS) was calculated, and other traditional risk factors were also documented.ResultsPlasma levels of several inflammatory markers and vWF were significantly but comparably elevated in RA and IBD compared with controls, except for a higher level of C-reactive protein (CRP) in RA than IBD. Compared to controls, FRS, body mass index, waist circumference, and triglycerides were increased in RA, but not in IBD. baPWV did not significantly differ among 3 groups, while ABI was modestly but significantly lower in IBD than controls. Circulating markers (macrophage migration inhibitory factor, tumour necrosis factor-α, CRP, and vWF) were significantly associated with baPWV. However, traditional risk factors (age, systolic blood pressure, body mass index, diabetes and triglycerides) were the parameters associated with baPWV in multiple regression analyses (overall r = 0.866, p < 0.001).ConclusionsRA has a higher level of CRP and more pronounced traditional cardiovascular risk factors than IBD, which may contribute to the difference in their associations with cardiovascular disease and mortality. Traditional risk factors, rather than inflammation markers, are major predictors of arterial stiffness even in subjects with inflammatory disorders. Our results point to the importance of modifying traditional risk factors in patients with inflammatory disorders.

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.

Background Exercise improves cardiovascular health, but recent studies have found high-volume high-intensity exercise is associated with increased coronary artery calcification (CAC). While traditional risk factors are predictors of CAC, these are less common in athletes. Therefore, CAC in athletes may be driven by a different pathophysiology, related to factors such as exercise characteristics, diet, calcium homeostasis and inflammation. Since increased CAC scores are also prevalent in athletes without traditional risk factors, the standard risk prediction algorithms may not be appropriate for athletes. Purpose We aimed to identify predictors of CAC, by assessing the association of traditional cardiovascular and non-traditional risk factors with CAC in middle-aged and older athletes. Methods Participants of the Measuring Athlete’s Risk of Cardiovascular events 2 (MARC-2) study were included. CAC was assessed by computed tomography. Questionnaires including food frequency and stress questionnaires, blood biomarkers (cardiac biomarkers, mineral concentrations, inflammation and lipids) and blood pressure were collected. We assessed the association of risk factors with CAC using linear and logistic regression. Results We included 289 male athletes (60.0 [Q1–3 56.3–66.0] years old) with a lifelong weekly training load of 26 [17–35] MET-hours, BMI of 24.5 [22.9–26.6] kg/m2, systolic blood pressure of 139±18 mmHg, and reported 0.0 [0.0–8.0] smoking pack years. Twenty-nine % of athletes had a CAC score of 0, 40% 1–100, 18% 101–400, and 13% &amp;gt;400. Among traditional cardiovascular risk factors, higher age, systolic blood pressure, smoking pack years, and family history of coronary artery disease independently predicted greater CAC scores. Family history was the most important traditional risk factor. Among non-traditional risk factors, higher training loads, serum calcium and phosphate, and lower adjusted energy intake and fat percentage of energy intake independently predicted greater CAC scores. Lower proportion of fat in diet was the strongest predictor of greater CAC scores. The full model had higher accuracy in predicting CAC&amp;gt;100 (ROC-AUC 0.75, 95%CI [0.69–0.81]) and CAC&amp;gt;400 (0.83 [0.76–0.91]) than both traditional cardiovascular risk factors alone (0.71 [0.64–0.78], p=0.014, and 0.78 [0.69–0.87], p=0.018, respectively) and the cardiovascular risk algorithm SCORE2 (0.65 [0.58–0.72], p&amp;lt;0.001, and 0.72 [0.63–0.80], p=0.002, respectively). Conclusions Traditional cardiovascular risk factors and risk algorithms have low accuracy in predicting CAC in aging athletes. Non-traditional risk factors training load, energy intake, proportion of fat intake, serum calcium and serum phosphate were associated with CAC scores. The addition of these variables increased the accuracy of the prediction model, and the full model outperformed both traditional risk factors and SCORE2 in the prediction of CAC in athletes.

Background. Coronary artery disease (CAD) is a complex, multifactorial disease in which personality seems to play a role but with no definition in combination with other risk factors. Objective. To explore the nonlinear and simultaneous pathways between traditional and personality traits risk factors and coronary stenosis by Artificial Neural Networks (ANN) data mining analysis. Method. Seventy-five subjects were examined for traditional cardiac risk factors and personality traits. Analyses were based on a new data mining method using a particular artificial adaptive system, the autocontractive map (AutoCM). Results. Several traditional Cardiovascular Risk Factors (CRF) present significant relations with coronary artery plaque (CAP) presence or severity. Moreover, anger turns out to be the main factor of personality for CAP in connection with numbers of traditional risk factors. Hidden connection map showed that anger, hostility, and the Type D personality subscale social inhibition are the core factors related to the traditional cardiovascular risk factors (CRF) specifically by hypertension. Discussion. This study shows a nonlinear and simultaneous pathway between traditional risk factors and personality traits associated with coronary stenosis in CAD patients without history of cardiovascular disease. In particular, anger seems to be the main personality factor for CAP in addition to traditional risk factors.

People living with HIV (PLWH) have increased risks of non-communicable diseases, especially cardiovascular diseases. Current HIV clinical management guidelines recommend regular cardiovascular risk screening, but the risk equation models are not specific for PLWH. Better tools are needed to assess cardiovascular risk among PLWH accurately. We performed a prospective study to determine the performance of automatic retinal image analysis in assessing coronary artery disease (CAD) in PLWH. We enrolled PLWH with ≥1 cardiovascular risk factor. All participants had computerized tomography (CT) coronary angiogram and digital fundus photographs. The primary outcome was coronary atherosclerosis; secondary outcomes included obstructive CAD. In addition, we compared the performances of three models (traditional cardiovascular risk factors alone; retinal characteristics alone; and both traditional and retinal characteristics) by comparing the area under the curve (AUC) of receiver operating characteristic curves. Among the 115 participants included in the analyses, with a mean age of 54 years, 89% were male, 95% had undetectable HIV RNA, 45% had hypertension, 40% had diabetes, 45% had dyslipidemia, and 55% had obesity, 71 (61.7%) had coronary atherosclerosis, and 23 (20.0%) had obstructive CAD. The machine-learning models, including retinal characteristics with and without traditional cardiovascular risk factors, had AUC of 0.987 and 0.979, respectively and had significantly better performance than the model including traditional cardiovascular risk factors alone (AUC 0.746) in assessing coronary artery disease atherosclerosis. The sensitivity and specificity for risk of coronary atherosclerosis in the combined model were 93.0% and 93.2%, respectively. For the assessment of obstructive CAD, models using retinal characteristics alone (AUC 0.986) or in combination with traditional risk factors (AUC 0.991) performed significantly better than traditional risk factors alone (AUC 0.777). The sensitivity and specificity for risk of obstructive CAD in the combined model were 95.7% and 97.8%, respectively. In this cohort of Asian PLWH at risk of cardiovascular diseases, retinal characteristics, either alone or combined with traditional risk factors, had superior performance in assessing coronary atherosclerosis and obstructive CAD. People living with HIV in an Asian cohort with risk factors for cardiovascular disease had a high prevalence of coronary artery disease (CAD). A machine-learning-based retinal image analysis could increase the accuracy in assessing the risk of coronary atherosclerosis and obstructive CAD.

Background:Well-developed coronary collateral circulation usually results in fewer infarct size, improved cardiac function, and fewer mortality. Traditional coronary risk factors (diabetes, hypertension, and smoking) have some effects on coronary collateral circulation. However, the association between these risk factors and coronary collateral circulation are controversial. Given the confusing evidences regarding traditional cardiovascular risk factors on coronary collateral circulation, we performed this meta-analysis protocol to investigate the relationship between traditional risk factors of coronary artery disease and coronary collateral circulation.Methods:MEDINE, EMBASE, and Science Citation Index will be searched to identify relevant studies. The primary outcomes of this meta-analysis are well-developed coronary collateral circulation. Meta-analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) of traditional coronary risk factors (diabetes, smoking, hypertriton). Pooled ORs were computed as the Mantel–Haenszel-weighted average of the ORs for all included studies. Sensitivity analysis, quality assessment, publication bias analysis, and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) will be performed to ensure the reliability of our results.Results:This study will provide a high-quality synthesis of current evidence of traditional risk factors on collateral circulation.Conclusion:This conclusion of our systematic review and meta-analysis will provide evidence to judge whether traditional risk factors affects coronary collateral circulation.Ethics and dissemination: Ethical approval is not required because our systematic review and meta-analysis will be based on published data without interventions on patients. The findings of this study will be published in a peer-reviewed journal.

Association of Lipoprotein Subfractions and Coronary Artery Calcium In Patient at Intermediate Cardiovascular Risk