Risk Of Cardiovascular Events In Patients Research Articles

Patient-specific multifactorial mortality risk assessment using classification and regression tree analysis in the context of ambulatory blood pressure monitoring.

Ambulatory blood pressure monitoring is essential for understanding blood pressure patterns beyond clinical visits, aiding in risk assessment, treatment evaluation, and managing hypertension. This retrospective cohort study aimed to identify risk factors for all-cause mortality and major cardiovascular events in patients who underwent ambulatory blood pressure monitoring. Eligible participants aged 18 or older, with an estimated glomerular filtration rate (eGFR) > 60ml/min/1.73m2, who underwent ambulatory blood pressure monitoring for various reasons, were included in the study. Data were gathered through telephone interviews, electronic health records, and the national health record system. Descriptive analysis and classification and regression tree modeling were used to uncover significant risk factors related to all-cause mortality and cardiovascular events, and to assess the model's performance compared to traditional Cox survival analysis. The study included 1291 patients, primarily male (51.8%) with a mean age of 61.1 ± 15.2years. During a mean follow-up of 46.9months, 76 (5.9%) patients died of any cause, and 195 (15.1%) had a cardiovascular event. The highest survival rates were observed in patients with a diastolic blood pressure (BP) dipping percentage between -2% and 29%, nighttime systolic BP variability below 32mmHg, and age below 72. Conversely, smokers with a diastolic BP dipping percentage below -10% showed the lowest survival rates. The best cardiovascular outcomes were observed in patients with diastolic BP dipping above -11%, nighttime mean systolic BP < 144mmHg, no statin use, normotensive status, and daytime mean heart rate ≥ 60bpm. Conversely, the worst outcomes were seen in patients with diastolic BP dipping below -11% and a morning surge ≥ 14mmHg. In all-cause mortality and cardiovascular event analysis, the combined model demonstrated excellent calibration and predictive power, like the classification and regression tree model and traditional analysis. These findings highlight the potential of a combined model for assessing mortality and cardiovascular event risk in patients who have undergone ambulatory blood pressure monitoring.

Integration of Diabetes Mellitus and Hypertension on Major Cardiovascular Events: An Experience From a 15-year Follow-up Cohort Study in EMR.

Patients with hypertension and diabetes are more susceptible to cardiovascular diseases (CVD) and mortality. This study aimed to evaluate the individual and combined effects of hypertension and diabetes on cardiovascular events and mortality in a Middle Eastern population-based cohort. Fifteen-year follow-up data were collected for 6323 adults aged 35 years and older who were free from CVD at baseline. The subjects were categorized into different groups according to hypertension and diabetes at baseline. Cox proportional hazards regression was implemented to estimate hazard ratios (HRs) of hypertension and diabetes for cardiovascular events (CVE), CVD mortality, and all-cause mortality. Population-attributable hazard fraction (PAHF) was used to assess the proportion of hazards of CVE and mortality attributable to hypertension or diabetes. The incidence rates (95% CI) of CVE, CVE mortality, and all-cause mortality in the total population were 13.77(12.84-14.77), 3.01(2.59-3.49), and 9.92(9.15-10.77) per 1000 persons per year respectively. The HR of hypertension for CVE in the diabetic population was 1.98 (1.47-2.66) with a PAHF of 27.65(15.49-39.3). When the HRs and PAHF of diabetes were evaluated in hypertensive patients, they were statistically significant for CVE, CVE mortality, and all-cause mortality. Our study indicated that the joint effect of diabetes and hypertension is the dramatic increased risk of CVE. A considerable fraction of the excess risk of CVE in patients with diabetes was attributable to hypertension, on the other hand, diabetes was associated with a substantial hazard fraction of CVE and mortality in hypertensive patients.

Efficacy and Safety of Bempedoic Acid in Patients with High Cardiovascular Risk: An Update.

Statins play a significant role in the prevention of cardiovascular (CV) diseases (CVDs); however, non-adherence with statin treatment or statin intolerance (mainly attributed to muscleassociated side effects) is not uncommon. New agents such as bempedoic acid (BA) can provide more treatment options. BA is administered orally, once daily, at a dose of 180 mg in current clinical practice. It can decrease circulating low-density lipoprotein cholesterol (LDL-C) levels by nearly 30% as monotherapy or by 20% as an add-on to statins. CV outcome studies have shown that BA decreases major adverse CV event risk in patients with established CVD or high CV risk by 13%. When patients with high CV risk were analyzed alone, the risk reduction was 30%. Its side effects include a rise in serum uric acid levels and liver enzyme activity, whereas it does not increase diabetes risk as statins do. BA can be used as adjunctive therapy to statins in patients at high CV risk in whom lipid targets cannot be achieved or as an alternative to statins in patients with statin intolerance.

Role of Fenofibrate Use in Dyslipidemia and Related Comorbidities in the Asian Population: A Narrative Review.

Hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) persist despite statin therapy, contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk. Asian subjects are metabolically more susceptible to hypertriglyceridemia than other ethnicities. Fenofibrate regulates hypertriglyceridemia, raises HDL-C levels, and is a recommended treatment for dyslipidemia. However, data on fenofibrate use across different Asian regions are limited. This narrative review summarizes the efficacy and safety data of fenofibrate in Asian subjects with dyslipidemia and related comorbidities (diabetes, metabolic syndrome, diabetic retinopathy, and diabetic nephropathy). Long-term fenofibrate use resulted in fewer cardiovascular (CV) events and reduced the composite of heart failure hospitalizations or CV mortality in type 2 diabetes mellitus. Fenofibrate plays a significant role in improving irisin resistance and microalbuminuria, inhibiting inflammatory responses, and reducing retinopathy incidence. Fenofibrate plus statin combination significantly reduced composite CV events risk in patients with metabolic syndrome and demonstrated decreased triglyceride and increased HDL-C levels with an acceptable safety profile in those with high CV or ASCVD risk. Nevertheless, care is necessary with fenofibrate use due to possible hepatic and renal toxicities in vulnerable individuals. Long-term trials and real-world studies are needed to confirm the clinical benefits of fenofibrate in the heterogeneous Asian population with dyslipidemia.

Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes.

Elevated lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are both associated with adverse events in high-risk patients with established coronary artery disease (CAD). Currently, the association between Lp(a) levels and recurrent cardiovascular (CV) events (CVEs) remained undetermined in patients with different glucose status. Therefore, this study aimed to investigate the prognostic significance of Lp(a) levels for recurrent CVEs in high-risk CAD patients who suffered from first CVEs according to different glycemic metabolism. We recruited 5257 consecutive patients with prior CVEs and followed up for recurrent CVEs, including CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. Patients were assigned to low, medium, and high groups according to Lp(a) levels and further stratified by glucose status. During a median 37-month follow-up, 225 (4.28%) recurrent CVEs occurred. High Lp(a) was independently associated with recurrent CVEs [adjusted Hazard Ratio (HR), 1.57; 95% confidence interval (CI) 1.12-2.19; P = 0.008]. When participants were classified according to Lp(a) levels and glycemic status, high Lp(a) levels were associated with an increased risk of recurrent CVEs in pre-DM (adjusted HR, 2.96; 95% CI 1.24-7.05; P = 0.014). Meanwhile, medium and high Lp(a) levels were both associated with an increased risk for recurrent CVEs in DM (adjusted HR, 3.09; 95% CI 1.30-7.34; P = 0.010 and adjusted HR, 3.13, 95% CI 1.30-7.53; P = 0.011, respectively). This study demonstrated that elevated Lp(a) levels were associated with an increased recurrent CVE risk in patients with CAD, particularly among those with pre-DM and DM, indicating that Lp(a) may provide incremental value in risk stratification in this population.

Omega-3 supplementation effects on cardiovascular risk and inflammatory profile in chronic kidney disease patients in hemodialysis treatment: An intervention study

Chronic Kidney Disease (CKD) is characterized by slow, progressive, and irreversible kidney function loss and the disease itself and hemodialysis treatment can predispose an inflammatory state that increased cardiovascular complications, being one of major mortality causes in kidney patients. The study purpose was to evaluate nutritional profile and impacts of w-3 fatty acid supplementation on inflammatory parameters and cardiovascular events risk in patients with CKD undergoing hemodialysis treatment. Non-randomized clinical trial, patients with CKD were randomly grouped into a control (n=29) and supplemented (n=30) group. Supplemented group patients were instructed to consume two w-3 capsules a day (2g/day) for 8 weeks for further analysis of pre- and post-supplementation C-reactive protein (CRP) and other blood parameters. To nutritional status assessment, anthropometric and bioelectrical impedance data were measured, carried out close to supplementation start. 59 patients were evaluated, 49.1% (n=29) were overweight and 70.7% (n=41) had high percentage of body fat. Comparing control versus supplemented groups after supplementation serum CRP levels have reduced, no differences were observed (p=0.716) nevertheless there was reduction in cardiovascular events risk according to C-reactive protein classification (p=0.004). Ferritin levels have improved in all groups. Changes in the levels of other biochemical markers hemoglobin, hematocrit, urea, creatinine, and Kt/v have happened. However, group that received w-3 showed an improvement in serum albumin levels (p=0.014), in addition to demonstrating greater adequacy classification of albumin after supplementation (p=0.022). Omega-3 supplementation have caused an improvement in albumin plasma levels suitableness in Chronic Kidney Disease patients, however, it did not demonstrate statistical effects to reducing CRP levels, although this helped to reduce cardiovascular risk.

Cardiovascular events risk in patients with systemic autoimmune diseases: a prognostic systematic review and meta-analysis.

Chronic inflammation is considered a risk factor for the development of atherosclerosis and cardiovascular (CV) events. We seek to assess the risk of CV events in patients with Systemic autoimmune diseases (SAD), such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Psoriasis (Ps) and Ankylosing Spondylitis (AS), compared with the general population. A systematic search of MEDLINE from inception up to May 2021 was performed. Observational studies including individuals with and without autoimmune diseases (SLE, RA, Ps, AS), which reported a measure of association and variability for the effect of SAD on CV events, were included. The random effects meta-analysis was performed using the Hartung-Knapp-Sidik-Jonkman approach to obtain the pooled estimates. Cardiovascular Events including CV mortality, non-fatal myocardial infarction (MI), non-fatal stroke and coronary revascularization were the main outcomes evaluated. Fifty-four studies were selected, with a total of 24,107,072 participants. The presence of SAD was associated with an increased risk of CV mortality (HR 1.49 [95% CI 1.10-2.03]), non-fatal MI (HR 1.42 [95% CI 1.23-1.62]), and non-fatal stroke (HR 1.47 [95% CI 1.28-1.70]). RA, SLE, and Ps (particularly with arthritis) were significantly associated with a higher risk of MI and stroke. SAD was also associated with an increased risk of Major Adverse Cardiovascular Events (MACE) (HR 1.45 [95% CI 1.16-1.83]). Patients with SAD present an increased risk of CV morbidity and mortality, which should be considered when establishing therapeutic strategies. These findings support the role of systemic inflammation in the development of atherosclerosis-driven disease.

Clinical factors for predicting cardiovascular risk, need for renal replacement therapy, and mortality in patients with non–dialysis-dependent stage 3–5 chronic kidney disease from the Salford Kidney Study

BackgroundEstablished cardiovascular risk assessment tools lack chronic kidney disease–specific clinical factors and may underestimate cardiovascular risk in non–dialysis-dependent chronic kidney disease (CKD) patients.MethodsA retrospective analysis of a cohort of patients with stage 3–5 non–dialysis-dependent chronic kidney disease in the Salford Kidney Study (UK, 2002–2016) was performed. Multivariable Cox regression models with backward selection and repeated measures joint models were used to evaluate clinical risk factors associated with cardiovascular events (individual and composite cardiovascular major adverse cardiovascular events), mortality (all-cause and cardiovascular-specific), and need for renal replacement therapy. Models were established using 70% of the cohort and validated on the remaining 30%. Hazard ratios ([95% CIs]) were reported.ResultsAmong 2192 patients, mean follow-up was 5.6 years. Cardiovascular major adverse cardiovascular events occurred in 422 (19.3%) patients; predictors included prior history of diabetes (1.39 [1.13–1.71]; P = 0.002) and serum albumin reduction of 5 g/L (1.20 [1.05–1.36]; P = 0.006). All-cause mortality occurred in 740 (33.4%) patients, median time to death was 3.8 years; predictors included reduction of estimated glomerular filtration of 5 mL/min/1.73 m2 (1.05 [1.01–1.08]; P = 0.011) and increase of phosphate of 0.1 mmol/L (1.04 [1.01–1.08]; P = 0.021), whereas a 10 g/L hemoglobin increase was protective (0.90 [0.85–0.95]; P < 0.001). In 394 (18.0%) patients who received renal replacement therapy, median time to event was 2.3 years; predictors included halving of estimated glomerular filtration rate (3.40 [2.65–4.35]; P < 0.001) and antihypertensive use (1.23 [1.12–1.34]; P < 0.001). Increasing age, albumin reduction, and prior history of diabetes or cardiovascular disease were risk factors for all outcomes except renal replacement therapy.ConclusionsSeveral chronic kidney disease–specific cardiovascular risk factors were associated with increased mortality and cardiovascular event risk in patients with non–dialysis-dependent chronic kidney disease.Graphical abstract

A higher resting heart rate is associated with cardiovascular event risk in patients with type 2 diabetes mellitus without known cardiovascular disease.

A higher resting heart rate (RHR) is associated with an increased risk of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The aim of this study was to investigate the association between RHR and cardiovascular events in T2DM patients with diabetic retinopathy and without known cardiovascular disease. We analyzed the association between RHR and cardiovascular events, including coronary, cerebral, renal and vascular events or cardiovascular death in T2DM patients with retinopathy and hyperlipidemia without prior cardiovascular events who were enrolled in the EMPATHY study. Data from 4746 patients were analyzed. The median RHR was 76 bpm. Patients were divided into four groups based on their baseline RHR ( < 60, 60-69, 70-79, and ≥80 bpm). Patients with a higher RHR were more likely to be younger and had a higher body mass index, blood pressure value, HbA1c value, and estimated glomerular filtration rate and a lower B-type natriuretic peptide value; they also had a higher proportion of current smoking status, neuropathy, and nephropathy. After adjusting for confounders, including the aforementioned risk factors, a RHR of 70-79 bpm and a RHR ≥ 80 bpm were significantly associated with cardiovascular events (hazard ratio 1.50, 95% CI 1.03-2.20; and hazard ratio 1.62, 95% CI 1.11-2.36; respectively) compared to a RHR of 60-69 bpm. The analysis using restricted cubic splines indicated that the cardiovascular risk seemed to be similarly high when the RHR range was ≥70 bpm. In conclusion, in T2DM patients with diabetic retinopathy and without known cardiovascular disease, a high RHR, particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to a RHR of 60-69 bpm. High resting heart rate (RHR), particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to RHR 60-69 bpm in patients with type 2 diabetes mellitus (T2DM), diabetic retinopathy, and hyperlipidemia, but without known cardiovascular disease.

Effect of Integrative Chinese and Western Medicine Therapy on Long-Term Clinical Outcomes in Patients with Heart Failure: A Real-World Study Including 394 Patients.

Objective To explore the effect of integrative Chinese and Western medicine therapy on the clinical outcomes of patients with heart failure. Methods This is a retrospective cohort study in the real world. Patients were divided into “conventional therapy” and “integrative therapy” groups according to treatment modality. The occurrence of cardiovascular events (CVE) was determined during follow-up. Survival curves were plotted, and survival analysis was performed using Cox regression to report survival in both groups. Further subgroup tests were performed as sensitivity analyses. A Markov model was constructed to predict patients with distant heart failure conditions based on real follow-up data. Results Based on diagnostic criteria, 394 patients with heart failure were included. The integrative therapy group had (N = 181) older patients (P=0.005), higher proportion of renal insufficiency (P < 0.001), higher creatinine (P=0.040), hypersensitive C-reactive protein (P=0.007), N-terminal pro-B type natriuretic peptide (P=0.019) levels, more patients in cardiac function class IV (P=0.004), and longer hospital days (P=0.003) than the conventional therapy group (N = 213). Survival was better in the integrative therapy group than in the conventional therapy group (log-rank P < 0.001). Multifactorial Cox regression identified “conventional therapy” or “integrative therapy” as an independent factor affecting the risk of CVE in patients with heart failure, with the risk of CVE being lower in the integrative therapy group (HR = 0.322, 95% CI = 0.185–0.561). A subgroup analysis found no significant association between therapy modality and risk of CVE in older patients (age ≥65 years, P=0.210) and those who had renal insufficiency (P=0.062). The Markov model predicted better cardiac function in the integrative therapy group than in the conventional therapy group at all time points (all P < 0.001). Conclusion In patients with heart failure, integrative therapy of Chinese and Western medicine had better long-term outcomes than conventional therapy. However, patients with advanced age and renal insufficiency had no significant advantage. Trials Registration. This trial is registered with China Clinical Trials Registry, ChiCTR2100050927, registered 8 September 2021, https://www.chictr.org.cn/showproj.aspx?proj=133451.

ANGPTL3 and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome and Obstructive Sleep Apnea.

Background The aim of this prospective study was to determine the impact of elevated ANGPTL3 (angiopoietin-like protein 3) on cardiovascular events (CVEs) following acute coronary syndrome (ACS) in patients with or without obstructive sleep apnea (OSA). Methods and Results A total of 1174 patients with ACS underwent successful percutaneous coronary intervention were included in this prospective cohort study (NCT03362385). Patients were categorized according to the apnea-hypopnea index (≥15 events/h, OSA) and further classified by ANGPTL3 levels. We analyzed the incidence of CVEs in patients with ACS according to the status of OSA and ANGPTL3. During a median of 3.1 years of follow-up, 217 (18.48%) CVEs occurred. The patients with ACS with OSA had higher ANGPTL3 levels than those without OSA (30.4 [20.9-43.2] versus 27.80 [19.1-41.5]ng/mL; P<0.001). In all patients with ACS, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with an increased risk of CVEs with hazard ratios (HRs) of 1.555 (95% CI, 1.010-2.498) and 2.489 (95% CI 1.613-3.840), respectively. When the status of OSA or not was incorporated in stratifying factors, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with a significantly higher risk of CVEs in patients with ACS with OSA (HR, 1.916 [95% CI, 1.019-3.601] and HR, 2.692 [95% CI, 1.379-4.503]) but not without OSA. Moreover, adding ANGPTL3 to the Cox model increased C-statistic values by 0.035 and 0.029 in the OSA group and all patients with ACS, respectively, but was not statistically improved in patients with ACS without OSA. Conclusions In conclusion, our study demonstrates a predictive impact of plasma ANGPTL3 on cardiovascular risk in patients with ACS, especially in patients with ACS with OSA. It might be of clinical value in refining risk stratification and tailoring treatment of patients with ACS and OSA. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03362385.

Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease: the updated SMART2 algorithm.

AimsThe 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations.Methods and resultsIndividuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2–12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547–0.664] in BACS/BAMI to 0.772 (95% CI 0.659–0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options.ConclusionThe SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.

Association of Plasminogen Activator Inhibitor-1 and Cardiovascular Events Development in Patients with Prediabetes

Background. Plasminogen activator inhibitor-1(PAI-1) is a marker of endothelial dysfunction(ED) and a predictor of both the development of type 2 diabetes mellitus, and a cardiovascular event(CVE). Its role in the CVE development was sufficiently studied in patients without carbohydrate metabolism disorders, and understudied in patients with prediabetes.&#x0D; Aim: the research interest is the study of PAI-1 in patients with prediabetes and its effect on the CVE development.&#x0D; Materials and methods. The case-control study of 168 patients aged from 18 to 65 was carried out among the local population from January to December 2019.After clinical examination, patients were divided into 3 groups: group 1 (n=55)– patients with prediabetes and with CVE; group 2 (n=93) - patients with prediabetes and without CVE; the control group n=20.&#x0D; Results. Differences in PAI-1 level were found in groups 1 (Me=30718.6 pg/ml) and 2 (Me=24692.0 pg/ml; p≤0.001), even greater differences were found in both groups compared to the control one (p≤0.001).&#x0D; The correlation analysis has found in both group influence such IR indicators as fasting glucose, IR-HOMA index, glucagon, C-peptide to elevation of PAI-1. These findings indicate that with an elevation of the PAI-1 level, the concentration of fasting glucose, glucagon, C-peptide and scores of IR-HOMA index increase in both group.&#x0D; The Binary regression analysis has demonstrated, that an elevation of the PAI-1 biomarker increases the likelihood of CVE by 3.3 fold in patients with prediabetes (p≤0.01). In addition to, a model has been derived for assessing the risk of cardiovascular events in patients with prediabetes.&#x0D; Conclusions. Elevation of PAI-1 concentration is associated with insulin resistance which leads to ED, and further development risk of CVE in patients with prediabetes.

Expression of miR-1-3p, miR-16-5p and miR-122-5p as Possible Risk Factors of Secondary Cardiovascular Events.

Ischemic event in one arterial territory increases the risk of a subsequent ischemic event. Circulating microRNAs (miRs) emerge as a potential clinical tool to assess risk of subsequent atherothrombotic events such as cardiovascular death (CVD), myocardial infarction (MI) and ischemic stroke (IS). In this prospective study, we searched for athero-specific miRs related to cardiovascular event risk in patients with symptomatic coronary, carotid lesion, or both territories involvements. The choice of particular miRs was based on database research (Pub-Med, Bethesda, MD, USA) taking into consideration the relationship with development of atherosclerosis and potential prognostic value. Levels of circulating miRs (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were compared in 142 patients with an acute ischemic event resulting from carotid and/or coronary artery stenosis, who underwent revascularization for symptomatic lesion. A 6-year prospective evaluation of CVD/MI/IS risk was performed. Patients with two-territory as compared to single-territory involvement differed in levels of miR-1-3p (p = 0.016), miR-16-5p (p < 0.001), miR-34a-5p (p = 0.018), miR-122-5p (p = 0.007), miR-124-3p (p < 0.001) and miR-499-5p (p < 0.001). During follow-up, 62 (43.7%) episodes of CVD/MI/IS occurred. In multivariate Cox analysis, miR-122-5p (HR = 1.0006, 95%CI = 1.0001–1.0011) and peripheral artery disease (PAD) (HR = 2.16, 95%CI = 1.26–3.70) were associated with CVD/MI/IS risk; miR-1-3p (HR = 2.73, 95%CI = 1.22–6.12) and PAD (HR = 3.47, 95%CI = 1.88–6.41) with CVD; miR-122-5p (HR = 1.0001, 95%CI = 1.000–1.0002) and creatinine level (HR = 1.02, 95%CI = 1.01–1.04) with IS, and miR-16-5p (HR = 1.0004, 95%CI = 1.0001–1.0008) with MI. Expression of miR-1-3p, miR-16-5p and miR-122-5p during incident ischemia may be possible risk factors of secondary cardiovascular event(s).

Higher levels of anti-phosphorylcholine autoantibodies in early rheumatoid arthritis indicate lower risk of incident cardiovascular events

BackgroundThe increased risk of cardiovascular events (CVE) in rheumatoid arthritis (RA) is not fully explained by traditional risk factors. Immuno-inflammatory mechanisms and autoantibodies could be involved in the pathogenesis of atherosclerotic disease. It has been suggested that anti-phosphorylcholine antibodies (anti-PC) of the IgM subclass may have atheroprotective effects. Here, we aimed to investigate the association between levels of IgM anti-PC antibodies with CVE in patients with early RA.MethodsThe study population was derived from the BARFOT early RA cohort, recruited in 1994–1999. The outcome of incident CVE (AMI, angina pectoris, coronary intervention, ischemic stroke, TIA) was tracked through the Swedish Hospital Discharge and the National Cause of Death Registries. Sera collected at inclusion and the 2-year visit were analyzed with ELISA to determine levels of anti-PC IgM. The Kaplan-Meier estimates and Cox proportional hazards regression models were used to compare CV outcome in the groups categorized by baseline median level of IgM anti-PC.ResultsIn all, 653 patients with early RA, 68% women, mean (SD) age 54.8 (14.7) years, DAS28 5.2 (1.3), 68% seropositive, and without prevalent CVD, were included. During the follow-up of mean 11.7 years, 141 incident CVE were recorded.Baseline IgM anti-PC above median was associated with a reduction in risk of incident CVE in patients aged below 55 years at inclusion, HR 0.360 (95% CI, 0.142–0.916); in males, HR 0.558 (0.325–0.958); in patients with BMI above 30 kg/m2, HR 0.235 (0.065–0.842); and in those who did not achieve DAS28 remission at 1 year, HR 0.592 (0.379–0.924). The pattern of associations was confirmed in the models with AUC IgM anti-PC over 2 years.ConclusionProtective effects of higher levels of innate IgM anti-PC autoantibodies on CVE were detected in younger patients with RA and those at high risk of CVE: males, presence of obesity, and non-remission at 1 year.

Subclinical depression and anxiety as an additional risk factor for cardiovascular events in low- and moderate-risk patients: data from 10-year follow-up

Aim. To assess the contribution of anxiety (A) and depression (D) to the increased risk of cardiovascular events (CVEs) in patients with Systematic Coronary Risk Evaluation (SCORE) &lt;5% according to 10-year follow-up.Material and methods. The work included 190 patients with SCORErisk &lt;5%, examined in 2009-2010. In addition to the standard examination, a questionnaire was carried out using Hospital Anxiety and Depression Scale (HADS). In 2019, we contacted participants by telephone to identify CVEs over the past time: death from cardiovascular diseases (CVDs), acute myocardial infarction (MI), unstable angina, stroke, revascularization. The response was 86,3%.Results. CVEs occurred in 17 (10,2%) patients and included following outcomes: 3 deaths from CVDs, 6 acute MIs, 4 cases of unstable angina, 12 revascularizations. Patients with and without CVEs differed only in the depression level — 7 (5; 7) vs 5.0 (4; 5) points (p=0,0001). HADS-D score &gt;6 increased the probability of CVEs — odds ratio (OR) 2,9 (1,1-7,7). In individuals with HADS-D score &gt;6 and/or HADS-A score &gt;7, the probability of CVEs increased — OR 4,9 (1,4-17,9). A combination of impaired two or more parameters of the lipid profile, systolic blood pressure &gt;130 mm Hg and HADS-D score &gt;6 and/or HADS-A score &gt;7 increased the risk of CVE — OR 7,3 (2,48-21,36).Conclusion. Depression, including subclinical depression, is associated with an increased risk of CVEs in patients with a SCORE risk &lt;5%.

MON-193 Glucocorticoid Excess and Its Association with Metabolic and Cardiovascular Complications in Primary Aldosteronism

Objective: To investigate autonomous cortisol secretion in patients with primary aldosteronism and its effect on metabolism and cardiovascular events (CVE) in patients with primary aldosteronism (PA). Methods: This study included 163 patients with PA and 105 sex- and age-matched patients with essential hypertension (EH). Clinical and laboratory data were collected. The expression of cortisol synthase (CYP11B1) and aldosterone synthase (CYP11B2) was investigated in adenoma tissues from 44 patients with aldosterone-producing adenoma (APA) by employing immunohistochemistry. Results: 1) CYP11B2 was expressed in 36 patients with APA and was absent in 8 patients, while CYP11B1 immunoreactivity was detected in all tested patients with APA; 2) Compared with patients with EH, midnight cortisol concentration (104.81±90.86 vs 76.87±65.86), 24-h urine free cortisol level (726.04±309.87 vs 630.65±168.2), and cortisol level after 1mg-DST [35.6(27.6,75.73)vs 27.6(27.60,29.27)]were all significantly increased in patients with PA(all P<0.01); 3) Midnight cortisol concentration is positively associated with systolic blood pressure (SBP) (r=0.147 P<0.05), LDL-C (r=0.194 P<0.05), HOMA-IR (r=0.262 P<0.05), HOMA-β (r=0.313 P<0.05) and fasting insulin level (r=0.329 P<0.05) in patients with PA. In multiple linear regression analysis, midnight cortisol concentration was a postitive predictor for SBP (β=0.185 P<0.05), HOMA-IR (β=0.331 P<0.05) and HOMA-β (β=0.390 P<0.05); 4) Of the 163 patients with PA, 35 had a history of CVE, including 22 with stroke, eight with myocardial infarction, three with atrial fibrillation, and two with heart failure. The multivariate logistic-regression analyses revealed older age (OR 1.160 95%CI 1.041-1.294 P <0.001) and higher serum aldosterone level (OR 1.013 95%CI 1.000-1.026 P <0.05) were independent risk factors of CVE, serum cortisol level was not associated with the increased risk of CVE in patients with PA (OR 0.997 95%CI 0.985-1.009 P =0.570). Conclusion: Excess cortisol secretion was common in PA. Cortisol excretion is correlated with metabolic disorders, but not associated with increased risk of CVE in patients with PA.

The association between biologic agents and the risk of cardiovascular events in patients with psoriasis and psoriatic arthritis: A protocol for a systematic review and meta-analysis.

Background:Psoriasis (Pso) is a chronic, recurrent, and inflammatory disease involving genetic and immune factors. Psoriatic arthritis (PsA), accounting for 30% of Pso, is an inflammatory arthropathy. Pso and PsA are associated with increased cardiovascular events (CVEs). Biologic therapies for Pso and PsA are drawing arising attention for its therapeutic effects. Large evidences have shown that biologic agents could lower the risk of CVEs in patients with Pso and PsA. However, not all studies support this point. A systematic review is needed.Methods:Four databases (PubMed, Web of Science, The Cochrane Library, and EMBASE) will be searched from the inception to July 1st, 2019. Randomized controlled trials and observational studies (including case-control studies and cohort studies) reporting CVEs in patients with Pso and PsA treated with biologic agents will be included. The primary outcome is the incidence of CVEs. The secondary outcome is the incidence of each individually reported cardiovascular event. Study selection, data extraction, and assessment of quality will be conducted independently by 2 reviewers. RevMan5.3.5 software will be used for data synthesis.Results:The results of this study will provide evidence for the effect of biologic agents on the risk of CVEs in patients with Pso and PsA, so as to further provide guidance for clinical management.Conclusion:The findings of this study will be published in a peer-reviewed journal.PROSPERO registration number:CRD42019142778

Baseline and on-statin treatment lipoprotein(a) levels for predicting cardiovascular events in patients with familial hypercholesterolemia

Background and aimsLipoprotein(a) [Lp(a)] has been considered as a causal risk factor for cardiovascular disease (CVD) in the general population and levels vary in different ethnicities. However, no systemic analysis is currently available regarding the relation of plasma Lp(a) levels to cardiovascular events (CVEs) in Chinese patients with heterozygous familial hypercholesterolemia (HeFH). MethodsThree hundred and ninety-three patients with HeFH undergoing Lp(a) measurement at baseline were consecutively enrolled and followed prospectively for an average of 36.5 months. Lp(a) levels were determined using an immunoturbidimetry assay. Cox regression analysis with adjusted hazard ratios (HRs) and Kaplan-Meier analysis were used to evaluate the prognostic value of Lp(a) on CVEs. ResultsThirty-five events occurred during follow-up. Lp(a) was significantly higher in patients with CVEs (53.3 mg/dL versus 31.7 mg/dL, p < 0.001). In Kaplan-Meier analysis, patients with upper tertile of Lp(a) had a significant lower event-free survival (p = 0.004). After adjusting for confounding risk factors, per log unit increase in baseline Lp(a) was independently associated with CVEs [HR: 2.03(1.28–3.21), p = 0.002]. HRs remained unchanged after accounting for hard endpoints and did not vary too much in several relevant subgroups. Adding Lp(a) to the Cox model led to a significant improvement in C-statistic, net reclassification and integrated discrimination. Moreover, HR for upper versus lower tertile of change in Lp(a) was 2.68 (1.11–6.48) for CVEs after one year. ConclusionsBoth baseline and on-statin treatment Lp(a) levels were associated with an increased risk of CVEs in patients with HeFH, suggesting that Lp(a) measurement might clinically help further risk stratification of FH patients.

P3645Prognosis in relation to high-sensitivity C-reactive protein levels in patients with non-obstructive coronary artery disease

Abstract Background It has been reported that coronary artery disease (CAD) is characterized by inflammation and non-obstructive CAD (NOCAD) increases the risk of cardiovascular events (CVEs) compared with ones with normal or near-normal coronary arteries (NNCA), even is similar to obstructive CAD (OCAD). We hypothesized that elevated high-sensitivity C-reactive protein (hs-CRP) may be linked to CVEs in those patients with NOCAD. Purpose To investigate the predictive role of hs-CRP in patients with NOCAD. Methods Of 7,746 consecutive patients with angina-like chest pain admissions, 4,662 eligible patients were enrolled who received coronary artery angiography (CAG) and followed up for the CVEs comprising all-cause mortality, myocardial infarction, stroke and late revascularization. According to the results of CAG, the patients were classified as NNCA group (&lt;20% stenosis, n=698, 15.0%), NOCAD group (20–49% stenosis, n=639, 14.3%), and OCAD group (≥50% stenosis, n=3325, 70.7%). They were further subdivided into 3 groups according to baseline hs-CRP levels (&lt;1, 1–3 and &gt;3 mg/L). Proportional hazards models were used to assess the risk of CVEs in all patients enrolled. Results A total of 338 patients (7.3%) experienced CVEs during an average of 13403 person-years follow-up. Patients with NOCAD and OCAD had higher rates of CVEs compared to those with NNCA (p&lt;0.05, respectively). In Cox's models after adjustment of confounders, the risk of CVEs elevated with the increasing degrees of CAD with hazard ratio of 2.01 [95% confidence interval (95% CI): 1.07–3.79, p=0.03] for patients with NOCAD and 2.81 (95% CI: 1.60–4.93, p&lt;0.001) for patients with OCAD compared with the NNCA group. Moreover, elevated hs-CRP levels were associated with the severity of coronary lesions and an elevated increased risk of CVEs in patients with NOCAD and OCAD compared those with NNCA (p&lt;0.05, respectively). Conclusions Patients with NOCAD had indeed worse outcomes and hs-CRP levels were positively in relation to the CVEs in those with NOCAD, which may help to the risk assessment in ones with NOCAD. Acknowledgement/Funding This study was partly supported by Capital Health Development Fund (201614035) and CAMS Innovation Fund for Medical Sciences (2016-I2M-1-011) awarded