Prospective Comparison of Plasma Biomarker and Traditional Risk Factor Profiles for Incident Isolated Atherosclerotic Disease and Incident Isolated Abdominal Aortic Aneurysm

Background: Traditional risk factors for atherosclerotic disease (AD) are well-known, of which some are relevant also for abdominal aortic aneurysms (AAA). The present study compares the importance of plasma biomarkers and traditional risk factor profiles for incident AD without concomitant AAA (isolated AD) and AAA without concomitant AD (isolated AAA) during long-term follow-up.Methods: In the Malmö Diet and Cancer Study—cardiovascular cohort, 5,381 participants were free from atrial fibrillation or flutter, AD (coronary artery disease, atherothrombotic ischemic stroke, carotid artery disease, or peripheral artery disease), and AAA underwent blood sampling under standardized fasting conditions between 1991 and 1994. Cox proportional hazards regression analysis was used to calculate hazard ratios (HR) with 95% CIs.Results: During a median follow-up of 23.1 years, 1,152 participants developed isolated AD, and 44 developed isolated AAA. Adjusted HR for lipoprotein-associated phospholipase A2 (mass) (HR 1.53, 95% CI 1.14–2.04 vs. HR 1.05, 95% CI.99–1.12) was higher for incident isolated AAA compared to incident isolated AD, respectively. Mid-regional pro-adrenomedullin (MR-proADM) was associated with incident isolated AD (HR 1.17, 95% CI 1.1–1.25) and incident isolated AAA (HR 1.47, 95% CI 1.15–1.88). MR-proADM was correlated (r = 0.32; p < 0.001) to body mass index (BMI), and BMI was associated with increased risk of incident isolated AAA (HR 1.43, 95% CI 1.02–2). No participant with diabetes mellitus (DM) at baseline developed isolated AAA (0/44), whereas DM was associated with an increased risk of isolated AD (HR 2.57, 95% CI 2.08–3.18). Adjusted HR for male sex (HR 4.8, 95% CI 2.42–9.48, vs. HR 1.76, 95% CI 1.56–1.98) and current smoking (HR 4.79, 95% CI 2.42–9.47 vs. HR 1.97, 95% CI 1.73–2.23) were higher in the incident isolated AAA group compared to the incident isolated AD group, respectively.Conclusions: The data supports the view that components of vascular inflammation and cardiovascular stress drives AAA development, whereas glycated cross-links in abdominal aortic wall tissue may have a plausible role in reducing AAA risk in individuals with DM.

A STUDY OF RHEUMATOID FACTOR AND ITS RELATION TO ISCHEMIC HEART DISEASE

INTRODUCTION : Ischemic heart disease (IHD) is a leading cause of death in the world. Most of the subjects with IHD may have traditional risk factors including diabetes,smoking, hypertension,obesity. Rheumatoid Factor (RF) has been associated with an increased likelihood of developing IHD.Presence of RF in general population may identify the subjects with a similar immune pathology to patients with RA, who may also share an increased likelihood of developing IHD and that RF may have special role in the pathogenisis of IHD . MATERIALS AND METHODS: Cross sectional observational study done from September 2020 to August 2021 in Kamineni institute of medical sciences Narketpally, included 100 patients, who were all RF positive.During the study period they were evaluated for IHD by E CG and ECHO.Those who are included in the study were evaluated for traditional risk factors h/o Diabetes, smoking,family h/o IHD and hypertension,BMI for Obesity and features of RA. A resting 12 lead ECG was carried out for features of IHD.The following ch anges in the ECG were taken as marker of ischemia: 1)The combination of ST elevation in a set of leads and reciprocal ST depression in a set of leads.2) Inversion of T with ST still being elevated.3) Presence of pathological Q waves RESULTS : Of the 100 patients with RF positivity, there were 65 females and 35 males. Ischemic changes in ECG in presence of RF with traditional risk factor is n=12 (75%) M 8(50%) F-- 4(25%) and RF without traditional risk factor is n=4 (25%) M-4(25%) F-0.In the present study there were 16 patients who had RF positivity with Ischemic changes in ECG. 12 were males and 4 were females. CONCLUSIONS: RF per se can be considered as one of the risk factor for Ischemic heart disease in males. Ÿ RF associated with traditional risk factors increase the prevalence of IHD. Ÿ Though more female patients have positive RF, they are not vulnerable to IHD.

Risk Stratification Tool for Ischemic Stroke: A Risk Assessment Model Based on Traditional Risk Factors Combined With White Matter Lesions and Retinal Vascular Caliber

Objective: This study aims to establish a risk assessment model based on traditional risk factors combined with the Fazekas classification of white matter lesions and retinal vascular caliber for screening the patients at high risk of ischemic stroke.Methods: This study included 296 patients (128 cases of ischemic stroke and 168 cases in the normal control group). The basic data of the patients were collected. Color fundus photography was performed after pupil dilation, and the retinal vascular caliber was measured using semiautomated vascular measurement software (IVAN Software, Sydney, Australia). The severity of white matter lesions (WML) on cranial nuclear magnetic fluid-attenuated inversion recovery images were assessed using the Fazekas scale. Moreover, logistic regression analysis was used to establish different risk assessment models for ischemic stroke. The effects of models were evaluated through the receiver operating characteristic (ROC) curve and the Delong test compared area under the curve.Results: The sensitivity and specificity of models 1 (the traditional risk factor model), 2 (the retinal vascular caliber model), 3 (the WML model), and 4 (the combined the traditional risk factor, WML and central retinal artery equivalent (CRAE) model) were 71 and 55%, 48 and 71%, 49 and 67%, and 68 and 68.5% with areas under the curve of 0.658, 0.586, 0.601, and 0.708, respectively. The area under the receiver operating characteristic curve in models 1, 2, 3, and 4 showed statistically significant differences. Moreover, no statistical significance exists in the pairwise comparison of other models.Conclusion: The risk assessment model of ischemic stroke combined with Fazekas grade of WML and CRAE is superior to the traditional risk factor and the single-index model. This model is helpful for risk stratification of high-risk stroke patients.

The association between longevity associated FOXO3 allele and heart disease in Septuagenarians and Octogenarians: The SONIC study

The G allele of FOXO3 gene (Single nucleotide polymorphism – SNP; rs2802292) is strongly associated with human longevity. However, knowledge of the effect of FOXO3 in older populations, men or women, with heart disease is limited. This cross-sectional study in Japan included 1836 older adults in the 70 and 80-year-old groups. DNA samples isolated from buffy coat samples of peripheral blood were used to genotype FOXO3 (rs2802292). Self-reports were used to obtain heart disease data according to physician diagnosis. Multiple logistic regression was used to test the association by adjusting for the traditional risk factor of heart disease. The prevalence of heart disease in women FOXO3 G allele carriers was higher than non-carriers (16.7 vs. 11.6%, p=.022). The prevalence of coronary heart disease was lower for FOXO3 G carriers in the 70-year-old group for both sexes (men: 9.3 vs. 4.3%, p=.042, and women: 10 vs. 9%, p=.079, respectively). The G allele was negatively associated with heart disease after adjusting for diabetes, hypertension, dyslipidemia, and smoking in men (odds ratio (OR)= 0.70, 95%confidence intervals (CI), 0.49-0.99, p=.046), although the association was weaker after full adjustment. In contrast, women carriers of the FOXO3 G allele showed a positive association with heart disease after total adjustment (OR= 1.49, 95%CI, 1.00-2.21, p=.049). In conclusion, the longevity associated G allele of FOXO3 was observed to have contrasting associations with heart disease prevalence according to sex in older Japanese. To further confirm this association, a longitudinal study and a large sample size will be required.

Stroke risk in arthritis: A systematic review and meta-analysis of cohort studies

Background and objective Stroke is a major contributor to the global burden of disease. Although numerous modifiable risk factors (RF) for stroke have been identified, some remain unexplained. Increasing studies have investigated stroke risk in arthritis, but their results are inconsistent. We aimed to synthesize, quantify, and compare the risk of stroke for the major types of arthritis in cohort studies by using a systematic review and meta-analysis approach. Methods We searched Chinese and English databases to identify relevant studies from inception to April 30, 2020. Only studies adjusting at least for age and sex were included. We calculated pooled effect estimates for relative risk (RR) and 95% confidence interval (CI) and identified potential sources of heterogeneity and publication bias. Results A total of 1,348 articles were retrieved, and after an preliminary screening of titles and abstracts, 69 were reviewed for full text, and finally, 32 met the criteria for meta-analysis. Stroke risk in arthritis was significantly increased in studies adjusting for age and sex (RR = 1.36, 95% CI: 1.27–1.46) and for at least one traditional risk factor (RR = 1.40, 95% CI: 1.28–1.54). The results of studies stratified by stroke subtype were consistent with the main finding (ischemic stroke: RR = 1.53, 95% CI: 1.32–1.78; hemorrhagic stroke: RR = 1.45, 95% CI: 1.15–1.84). In subgroup analysis by arthritis type, stroke risk was significantly increased in rheumatoid arthritis (RR = 1.38, 95% CI: 1.29–1.48), ankylosing spondylitis (RR = 1.49, 95% CI: 1.25–1.77), psoriatic arthritis (RR = 1.33, 95% CI: 1.22–1.45), and gout (RR = 1.40, 95% CI: 1.13–1.73) but not osteoarthritis (RR = 1.03, 95% CI: 0.91–1.16). Age and sex subgroup analyses indicated that stroke risk was similar by sex (women: RR = 1.47, 95% CI: 1.31–1.66; men: RR = 1.44, 95% CI: 1.28–1.61); risk was higher with younger age (<45 years) (RR = 1.46, 95% CI: 1.17–1.82) than older age (≥65 years) (RR = 1.17, 95% CI: 1.08–1.26). Conclusions Stroke risk was increased in multiple arthritis and similar between ischemic and hemorrhagic stroke. Young patients with arthritis had the highest risk.

V1a and V1b Vasopressin Receptors Within the Paraventricular Nucleus Contribute to Hypertension in Male Rats Exposed to Chronic Mild Unpredictable Stress

Depression is an independent non-traditional risk factor for cardiovascular disease and mortality. The chronic unpredictable mild stress (CMS) rat model is a validated model of depression. Within the paraventricular nucleus (PVN), vasopressin (VP) via V1aR and V1bR have been implicated in stress and neurocardiovascular dysregulation. We hypothesized that in conscious, unrestrained CMS rats vs control, unstressed rats, PVN VP results in elevated arterial pressure (MAP), heart rate and renal sympathetic nerve activity (RSNA) via activation of V1aR and/or V1bR. Male rats underwent four weeks of CMS or control conditions. They were then equipped with hemodynamic telemetry transmitters, PVN cannula, and left renal nerve electrode. V1aR or V1bR antagonism dose-dependently inhibited MAP after VP injection. V1aR or V1bR blockers at their ED50 doses did not alter baseline parameters in either control or CMS rats, but attenuated the pressor response to VP microinjected into PVN by ~50%. Combined V­1aR and V1bR inhibition completely blocked the pressor response to PVN VP in control but not CMS rats. CMS rats required combined maximally inhibitory doses to block either endogenous VP within the PVN or responses to microinjected VP. Compared with unstressed control rats, CMS rats had higher plasma VP levels and greater abundance of V1aR and V1bR transcripts within PVN. Thus, the CMS rat model of depression results in higher resting MAP, heart rate and RSNA which can be mitigated by inhibition of vasopressinergic mechanisms involving both V1aR and V1bR within the PVN. Circulating VP may also play a role in the pressor response.

Acute Coronary Syndrome in Well Trained Young Adult: A Rare Cases

Acute Coronary Syndrome (ACS) has been observed in the older population (>40 years old), sedentary lifestyle and unhealthy behaviour. Recently, there is an increase of ACS reported in the younger population even without a sedentary lifestyle.We report a case of awell-trained 25-years old man thatcame with late presentation of ST elevation myocardial infarction (STEMI) occurred 10 minutes after vigorous exercise. His traditional risk factor was a smoker.Electrocardiogram (ECG) showed a pathological Q wave in V1-V3 and T wave inversion in V1-V6 with elevated cardiac biomarker. Primary percutaneous coronary intervention (PPCI) was performed due to prolonged chest pain and it showed subtotal occlusion in mid left anterior descending artery (LAD) with high thrombus burden. One drug eluting stent (DES) was implanted at mid LAD and GPIIb/IIIa inhibitor and low molecule weight heparin was given with good clinical result.

Predictive Value of Coronary Artery Calcium Score Categories for Coronary Events Versus Strokes: Impact of Sex and Race

Background: Coronary artery calcium (CAC) predicts atherosclerotic cardiovascular disease (ASCVD) events, inclusive of coronary heart disease (CHD) and stroke, and is a decision-making aid for primary prevention. The predictive value of CAC categories for CHD and stroke separately and across sex and race groups of an asymptomatic population is unclear. Methods: White, Black, and Hispanic participants of MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) underwent CAC measurement at enrollment and were followed for incident ASCVD events. Ten-year CHD-to-stroke incidence ratios across CAC score categories 0, 1 to 99, and ≥100 were assessed. Associations of CAC with incident CHD and stroke events were evaluated using multivariable-adjusted Cox models and multiplicative interactions of CAC with sex/race were tested. Results: Among 7042 participants (mean age, 57 years, 54% women, 36% Black, 23% Hispanic, 49% CAC=0, 19% CAC ≥100), 574 incident ASCVD events (333 CHD and 241 stroke) were observed over 12.3-year follow-up. Ten-year CHD-to-stroke incidence ratio increased significantly across CAC categories in men, women, Whites, Blacks, and Hispanics (all P <0.001). High CAC burden (score ≥100) was independently associated with ASCVD and CHD risk in all groups and with stroke risk in the overall cohort and Blacks. No sex- or race-based CAC interactions for ASCVD, CHD, and stroke events were observed. Adding CAC to a traditional risk factor model improved risk discrimination and reclassification for CHD but not for stroke events. Conclusions: In 2 population-based cohorts of asymptomatic individuals, 10-year CHD-to-stroke incidence ratio was higher with increasing CAC score categories across sex and race groups, and CAC was consistently a better predictor of CHD than stroke. High CAC burden comparably associated with ASCVD risk across sex and race groups.

Life-threatening hypertriglyceridemia-induced pancreatitis related to alectinib successfully treated by plasmapheresis: A review of the literature on metabolic toxicities associated with anaplastic lymphoma kinase inhibitors

Introduction Actionable mutations are tested as standard of care for all new metastatic non-small cell lung cancers. Tumors harboring an anaplastic lymphoma kinase mutation respond to tyrosine kinase inhibitors targeting anaplastic lymphoma kinase pathway. Patients are monitored for common adverse effects, although we occasionally encounter unexpected side effects. Case report A 52-year-old male presented with a right hilar lung mass, and workup revealed a stage IIIA adenocarcinoma. He underwent treatment with concurrent chemoradiation; however, disease recurred one year later with a right hilar mass and contralateral mediastinal lymphadenopathy, biopsy of which resulted positive for adenocarcinoma. Molecular analysis showed anaplastic lymphoma kinase rearrangement and alectinib was started. Six months into therapy, he presented with hematochezia, nausea, and epigastric pain and was diagnosed with acute pancreatitis. Triglyceride level resulted above the measurable level at >5680mg/dL, thought to be the inciting event of pancreatitis. Management and outcome: Despite treatment with intravenous hydration, insulin infusion, and antibiotics, he decompensated with development of respiratory failure, shock requiring intensive care. Therapeutic plasmapheresis was initiated due to persistently elevated triglyceride. Following the third plasmapheresis, triglyceride level decreased to 359 mg/dL. With aggressive multidisciplinary management, he made a complete recovery. Follow-up imaging studies at three and six months show a stable mass-like abnormality in the right hilum without evidence of disease progression. Discussion Prior to starting alectinib, our patient’s triglyceride level was 420 mg/dL. While he consumed alcohol, he had no other traditional risk factor. To our knowledge, this is the first reported case of hypertriglyceridemia-induced acute pancreatitis related to treatment with an anaplastic lymphoma kinase inhibitor.