Risk Of Recurrent Cardiovascular Events Research Articles

Central and Branch Retinal Artery Occlusion-Do They Harbor the Same Risk of Further Ischemic Events?

Purpose: Retinal artery occlusion (RAO) is associated with an increased risk of cardiovascular events such as ischemic stroke and myocardial infarction, but whether different RAO subtypes such as central retinal artery occlusion (CRAO) or branch retinal artery occlusion (BRAO) carry similar risk of these events is unclear. Our aim was to determine whether the risk of cardiovascular events differs between CRAO and BRAO. Methods: This single-center, retrospective study included 131 patients hospitalized in our clinic in 2010–2020 with CRAO or BRAO confirmed by ophthalmic examination. Data on demographics, previous ischemic stroke and myocardial infarction, comorbidities, the results of echocardiographic and ultrasound carotid artery examinations and laboratory tests were assessed. Data on ischemic stroke, myocardial infarction, and all-cause mortality occurring after RAO were obtained from the Polish National Health Service, which collects data on all publicly funded hospitalizations. Using these data, Kaplan-Meier analyses and Cox proportional hazard regression were performed. Results: Ischemic stroke occurred in 9.9% of patients after RAO: 10.6% in the CRAO group and 8.1% in the BRAO group (p = 0.662). Myocardial infarction occurred in 2.3% of patients after RAO: 2.1% in the CRAO group and 2.7% in the BRAO group (p = 0.843). All-cause mortality occurred in 22.9% of patients after RAO: 25.5% in the CRAO group and 16.2% in the BRAO group (p = 0.253). The composite endpoint of ischemic stroke, myocardial infarction, and all-cause mortality after RAO occurred in 28.2% of patients: 30.9% in the CRAO group and 21.6% in the BRAO group (p = 0.338). There was no difference between CRAO and BRAO in median time to ischemic stroke (32 vs. 76.4 months; p = 0.352), all-cause mortality (35.9 vs. 36.3 months; p = 0.876) or composite endpoint (37.5 vs. 41.5 months; p = 0.912) after RAO. The Kaplan-Meier analysis showed no differences between CRAO and BRAO in ischemic stroke, myocardial infarction, all-cause mortality, or the composite endpoint; similar results were obtained in analyses of patients with and without cardiovascular events before RAO. Conclusions: The prognosis for ischemic stroke, myocardial infarction, and all-cause mortality is similar in patients with CRAO and BRAO. Ischemic strokes occur with a similar frequency before and after RAO. Myocardial infarctions are observed significantly more frequently before an episode of RAO than after. The results of our study indicate that both CRAO and BRAO require expanded diagnostics to assess the risk of recurrent cardiovascular events, especially ischemic strokes, to implement appropriate prophylaxis and reduce mortality.

Long-term risk of death and recurrent cardiovascular events following acute coronary syndromes.

Estimates of the risk of recurrent cardiovascular events (residual risk) among patients with acute coronary syndromes have largely been based on clinical trial populations. Our objective was to estimate the residual risk associated with common comorbidities in a large, unselected, population-based cohort of acute coronary syndrome patients. 31,056 ACS patients (49.5%-non-ST segment elevation myocardial infarction [NSTEMI], 34.0%-ST segment elevation myocardial infarction [STEMI] and 16.5%-unstable angina [UA]) hospitalised in Alberta between April 2010 and March 2016 were included. The primary composite outcome was major adverse cardiovascular events (MACE) including: death, stroke or recurrent myocardial infarction. The secondary outcome was death from any cause. Cox-proportional hazard models were used to identify the impact of ACS type and commonly observed comorbidities (heart failure, hypertension, peripheral vascular disease, renal disease, cerebrovascular disease and diabetes). At 3.0 +/- 3.7 years, rates of MACE were highest in the NSTEMI population followed by STEMI and UA (3.58, 2.41 and 1.68 per 10,000 person years respectively). Mortality was also highest in the NSTEMI population followed by STEMI and UA (2.23, 1.38 and 0.95 per 10,000 person years respectively). Increased burden of comorbidities was associated with an increased risk of MACE, most prominently seen with heart failure (adjusted HR 1.83; 95% CI 1.73-1.93), renal disease (adjusted HR 1.52; 95% CI 1.40-1.65) and diabetes (adjusted HR 1.51; 95% CI 1.44-1.59). The cumulative presence of each of examined comorbidities was associated with an incremental increase in the rate of MACE ranging from 1.7 to 9.98 per 10,000 person years. Rates of secondary prevention medications at discharge were high including: statin (89.5%), angiotensin converting enzyme inhibitor/angiotensin receptor blocker (84.1%) and beta-blockers (85.9%). Residual cardiovascular risk following an acute coronary syndrome remains high despite advances in secondary prevention. A higher burden of comorbidities is associated with increased residual risk that may benefit from aggressive or novel therapies.

Association of triglyceride-rich lipoprotein-cholesterol with recurrent cardiovascular events in statin-treated patients according to different inflammatory status

Background and aimsThe association of triglyceride-rich lipoprotein-cholesterol (TRL-C) with recurrent cardiovascular events (RCVEs) has not been studied. Moreover, whether inflammation can affect TRL-C-associated cardiovascular risk is unknown. This study sought to examine the association between TRL-C and RCVEs, and whether this relationship is modulated by systemic inflammation in statin-treated patients with coronary artery disease (CAD) and nearly normal triglyceride. MethodsIn this study, 6723 CAD patients were consecutively enrolled, following a first CVE with triglyceride <2.3 mmol/L. Baseline lipid profile and high-sensitivity C-reactive protein (hsCRP) levels were determined. All patients were searched for RCVEs. The risk of RCVEs was assessed across quartiles (Q) of baseline TRL-C and further stratified by the median of hsCRP. ResultsOver a mean follow-up of 58.91 ± 17.79 months, 538 RCVEs were recorded. After adjustment for potential confounders, Q4 of TRL-C was significantly associated with the risk of RCVEs, which remained unchanged after hsCRP stratification. When subjects were grouped according to both TRL-C and hsCRP levels, patients with Q4 of TRL-C and hsCRP had the highest increase of the risk of RCVEs compared with the reference group (TRL-C Q1-3 and hsCRP Q1-3; HR, 1.90; 95%CI: 1.27–2.87). Furthermore, adding TRL-C to the original predicting model led to a slight but significant improvement. ConclusionsThe present analysis firstly showed that elevated TRL-C was associated with an increased RCVEs risk in statin-treated patients with CAD independent of systemic inflammation, suggesting that it might be a useful marker for risk stratification and a treatment target in this patient population.

The effects of polymorphisms in CYP2C19, ATP-binding cassette transporter B1, and paraoxonase-1 on clopidogrel treatment of Uygur patients following percutaneous coronary intervention.

Acute coronary syndrome (ACS) carries a high mortality in Uygur populations. Percutaneous coronary intervention (PCI) is a safe treatment for patients with ACS. Clopidogrel reduces the risk for recurrent cardiovascular events after PCI; however, its activity is influenced by cytochrome P450 (CYP450), ATP-binding cassette transporter B1 (ABCB1), and paraoxonase-1 (PON1). To assess the effects of genetic polymorphisms CYP2C19*2, *3, *17, ABCB1 C3435T, and PON1 Q192R along with clinical and demographic factors on variations in responses in Uygur patients following PCI. We enrolled 281 patients with PCI who were treated with clopidogrel and aspirin for at least 12months and recorded major adverse cardiovascular events (MACE) or bleeding within 1year. Approximately, 2mL of peripheral venous blood samples were used for genotype detection. Binary logistic regression with likelihood ratio forward stepwise analysis and redundancy analysis were carried out to identify factors associated with MACE. We analyzed risk factors including age, body mass index, smoking, hypertension, dyslipidemia, gender, alcohol consumption, diabetes mellitus, carriers of ABCB1 C3435T T allele, carriers of PON1 Q192R A allele, metabolizer phenotype of CYP2C19, number of targeted vessels, and number of stents. The CYP2C19 IMs (OR 3.546, 95% CI 1.972-6.375, P = 0.001), CYP2C19 PMs (OR 7.038, 95% CI 1.658-29.880, P = 0.008), and number of targeted vessels (OR 2.033, 95% CI 1.078-3.648, P = 0.026) were significantly associated with MACE. The CYP2C19 IMs, PMs, and the number of targeted vessels are essential factors associated with MACE risk in dual clopidogrel-treated Uygur population with ACS following PCI. These data provide valuable insights into the genetic polymorphisms affecting clopidogrel response among minority groups in China.

Changes over time in the prevention of recurrent coronary artery disease in everyday practice.

Patients with coronary artery disease (CAD) are at high risk of recurrent cardiovascular events, and risk factor control is crucial in this population. The aim of the study was to compare the implementation of the European Society of Cardiology guidelines regarding prevention of recurrent CAD in 2011 to 2013 with 2016 to 2017. The study included 5 hospitals with cardiology departments serving the city of Kraków and its surrounding districts. Consecutive patients with established CAD were interviewed 6 to 18 months after hospitalization in the years 2011 to 2013 and 2016 to 2017. We examined 616 patients in 2011 to 2013 and 388 in 2016 to 2017 (mean [SD] age, 64.7 [8.8] years vs 66.4 [8.4] years; P <0.01). After adjusting for covariates, the proportion of patients with high blood pressure decreased by 8.9% (95% CI, -15.6% to -2.1%) and the proportion of patients with high level of low‑ density lipoprotein cholesterol declined by 9.5% (95% CI, -16.7% to -2.2%) in 2016 to 2017 compared with 2011 to 2013, whereas the proportion of smoking patients (-0.2% [95% CI, -6% to 5.5%]) and those with high glucose levels (3.9% [95% CI, -2.2% to 10%]) and a body mass index of 25 kg/m2 or greater (3.8% [95% CI, -3.9% to 11.6%]) did not change. More patients were prescribed antiplatelets, β‑ blockers, angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, calcium antagonists, and anticoagulants in the second period. We observed an increase in the proportion of patients with CAD who were prescribed cardiovascular drugs, and consequently a slight improvement in the control of their blood pressure and low‑ density lipoprotein cholesterol. No changes were found regarding other main risk factors.

Temporal changes in the implementation of secondary prevention of coronary artery disease in every day practice

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf - Introduction Patients with coronary artery disease (CAD) are at high risk of recurrent cardiovascular events and control of their risk factors is crucial. Objectives Comparison of risk factors control in patients with CAD in 2016–2017 and 2011–2013. Patients and methods Five hospitals with cardiology departments serving the city and surrounding districts participated in the study. Consecutive patients hospitalized due to an acute coronary syndrome or a myocardial revascularization procedure were interviewed 6–18 months after hospitalization. The surveys were carried out in 2011–2013 and 2016–2017. Results We examined 616 patients in 2011–2013 and 388 in 2016–2017 (mean age: 64.7 ± 8.8 vs. 66.4 ± 8.4, P &amp;lt;0.01). After adjusting for covariates the proportion of patients with high blood pressure decreased by 8.9% (95% confidence intervals: -2.1% – -15.6%) and proportion of patients with high LDL cholesterol decreased by 9.5% (-2.2% – -16.7%) in 2016/2017 compared to 2011/2013, whereas the proportion of smoking patients (-0.2% [-6.0% – 5.5%]) and those with high glucose level (3.9% [-2.2% - 10.0%]) and with body mass index ≥25 kg/m2 (3.8% [-3.9% – 11.6%]) did not change significantly. The proportion of patients prescribed antiplatelets (6.5% [2.6% - 10.3%]), β-blockers (7.4% [2.2% - 12.6%]), angiotensin converting enzyme inhibitors or sartans (8.6% [2.9% – 14.3%]), calcium antagonists (8.1% [1.3 – 15.0]) and anticoagulants (5.5% [0.7% - 10.2%]) increased significantly. Conclusions In CAD patients, there was an increase of the proportion of patients with cardiovascular drugs prescribed and a slight improvement in the control of blood pressure and LDL cholesterol between 2011–2013 and 2016–2017. However, no significant changes were found for the other main risk factors. Patients who do not reach treatment goal Survey Smoking, % BP not at goal, %a BP ≥140/90 mmHg, % LDL cholesterol ≥1.8 mmol/l, % HbA1c ≥7.0%b, % Fasting glucose ≥7.0 mmol/l, % BMI≥25 kg/m2, % BMI≥30 kg/m2, % 2011-2013 19.0 50.3 43.0 71.9 14.1 15.9 81.2 33.8 2016-2017 16.2 40.7 39.2 60.3 14.9 20.2 83.4 38.3 P value 0.26 &amp;lt;0.01 0.24 &amp;lt;0.001 0.76 0.09 0.37 0.14 Differences adjusted for age, sex, index diagnosis, duration of education, professional activity (95% confidence intervals) 2016-2017 vs 2011-2013 -0.2(-6.0 - 5.5) -8.9(-15.6 - -2.1) -6.7(-14.3 - 1.0) -9.5(-16.7 - -2.2) 2.0(-3.4 - 7.4) 3.9(-2.2 - 10.0) 3.8(-3.9 - 11.6) 1.6 (-5.8 - 9.0) Abbreviations BMI, body mass index; BP, blood pressure; LDL, low-density lipoprotein a BP goal of &amp;lt;140/90mmHg (&amp;lt;130/80 mmHg in diabetics) in 2011–2013 and &amp;lt;140/90 mmHg (&amp;lt;140/85 mmHg in diabetics) in 2016–2017 b available for 362 patients in 2011-2013 and 383 patients in 2016-2017

Apparent treatment resistant hypertension and the risk of recurrent cardiovascular events and mortality in patients with established vascular disease

AimTo quantify the relation between apparent treatment resistant hypertension (aTRH) and the risk of recurrent major adverse cardiovascular events (MACE including stroke, myocardial infarction and vascular death) and mortality in patients with stable vascular disease. Methods7455 hypertensive patients with symptomatic vascular disease were included from the ongoing UCC-SMART cohort between 1996 and 2019. aTRH was defined as an office blood pressure ≥140/90 mmHg despite treatment with ≥3 antihypertensive drugs including a diuretic. Cox proportional hazard models were used to quantify the relation between aTRH and the risk of recurrent MACE and all-cause mortality. In addition, survival for patients with aTRH was assessed, taking competing risk of non-vascular mortality into account. ResultsA total of 1557 MACE and 1882 deaths occurred during a median follow-up of 9.0 years (interquartile range 4.8–13.1 years). Compared to patients with non-aTRH, the 614 patients (8%) with aTRH were at increased risk of cardiovascular mortality (HR 1.27; 95% CI 1.03–1.56) and death from any cause (HR 1.25; 95% CI 1.07–1.45) but not recurrent MACE (HR 1.13; 95% CI 0.95–1.34). At the age of 50 years, patients with aTRH after a first cardiovascular event on average had a 6.4 year shorter median life expectancy free of recurrent MACE than patients with non-aTRH. ConclusionIn hypertensive patients with clinically manifest vascular disease, aTRH is related to a higher risk of vascular death and death from any cause. Moreover, patients with aTRH after a first cardiovascular event have a 6.4 year shorter median life expectancy free of recurrent cardiovascular disease.

POS-259 MHR status as marker of 10-year risk and lifetime risk of recurrent Cardiovascular events in patients with CKD and Diabetes Mellitus

Patients with Chronic kidney disease (CKD) and Diabetes Mellitus are more exposed to atherosclerosis injury and have a higher risk of premature death from cardiovascular disease (CVD). Cardiovascular events are worsened by inflammation, oxidative stress, lipid accumulation and high-density lipoprotein cholesterol (HDL) reduction: individuals with perturbed lipid metabolism more frequently present monocyte profile changes, with an altered pro-inflammatory phenotype leading to a major risk of plaque formation and atherosclerosis. The alteration of the balance between monocyte and HDL, represented by the Monocyte/HDL ratio (MHR), is an easy way to evaluate the inflammatory status and to study appropriate strategies to treat high-risk patients. We evaluated 150 consecutive diabetic patients with CKD hospitalized in the Unit of Nephrology and Dialysis of the Policlinic G. Martino of Messina, Italy, with a history of CVD. We used the SMART-REACH SCORE, a model created to estimate life expectancy without recurrent cardiovascular events for individuals with a history of CVD. We performed a retrospective analysis of the MHR status of our patients to study its correlations with the 10-year risk and lifetime risk for myocardial infarction, stroke or vascular death, recurrent event and free life-expectancy if standard care is provided. In the entire cohort of patients, MHR appeared to be positively correlated with ten-year risk (ρ=0.469; P <0.0001) and lifetime risk of myocardial infarction, stroke, or CV death (ρ=0.428; P <0.0001). Furthermore, patients with higher MHR levels had a significantly smaller number of years of CVD-free life expectancy (ρ=-0.364; P <0.0001) (Figure 1). MHR can represent a valid tool to predict the recurrence of CVD in CKD patients with diabetes. This easy-to-perform marker of oxidative stress and cardiovascular risk can be used alone or in a multiple biomarker approach, improving the stratification and management of patients with comorbidities and risk of life- threatening conditions.

Predictive value of growth differentiation factor-15 in patients with myocardial infarction

Aim. To evaluate the prognostic value of growth differentiation factor-15 (GDF-15) in patients with acute myocardial infarction (MI).Material and methods. The study included 118 patients under the age of 70 with STand non-ST segment elevation myocardial infarction, who, in addition to routine examination, were tested for GDF-15 by enzyme-linked immunosorbent assay in the first 48 hours from the onset. The statistical significance of the differences in quantitative indicators was assessed by the Student’s t-test for a normal distribution and by the nonparametric U Mann-Whitney test for a non-normal distribution, while in qualitative indicators — by Pearson’s chisquared test. Pearson’s correlation coefficient and Spearman’s rank correlation coefficient were used as an indicator of strength of relationship between quantitative indicators.Results. The average GDF-15 level in patients with MI was 2,25±1,0 ng/ml. For 6 months of follow-up, 15,25% of patients were rehospitalized for unstable angina or recurrent myocardial infarction. The GDF-15 level in 82,6% of cases was in the third and fourth quartiles (≥2,07 ng/ml). All patients with recurrent MI had GDF-15 levels in the upper quartile (≥2б73 ng/ml). Patients with GDF-15 levels in the upper quartile had a significantly higher risk of rehospitalization (hazard ratio, 3,3 (95% CI, 1,65-6,76), p&lt;0,05) compared with patients with GDF-15 levels in other quartiles. The potential for the combined use of GDF-15 and N-terminal probrain natriuretic peptide (NT-proBNP) levels to assess the risk of readmission has been evaluated. Patients who had both GDF-15 and NT-proBNP levels in the upper quartiles (GDF-15&gt;2,73 ng/ml, NT-proBNP&gt;1418 pg/ml) had 4,8 times higher risk of rehospitalizations for unstable angina or recurrent myocardial infarction.Conclusion. In patients with MI, the determination of the GDF-15 level has prognostic value and may serve as an additional marker of the risk of recurrent cardiovascular events.

Lipid Management and 2-Year Clinical Outcomes in Japanese Patients with Acute Coronary Syndrome: EXPLORE-J.

Aim: The prevalence of atherosclerotic cardiovascular (CV) disease has risen in Japan due to increasing metabolic risk factors, including dyslipidemia. A positive linear correlation between low-density lipoprotein cholesterol (LDL-C) levels, incidence of CV events, and preventive effects of lipid-lowering therapy (LLT) is well established; however, data in Japan are limited. This analysis evaluated current lipid management practices and risk of recurrent CV events in Japanese post-acute coronary syndrome (ACS) patients. Methods: EXPLORE-J is a multicenter, 2-year observational study of hospitalized ACS patients in Japan. Results: At 2-year follow-up ( n =1944, mean age 66 years, 80.3% male), the cumulative incidence of major adverse cardiovascular events (MACE; death associated with myocardial infarction/cerebrovascular accident [CVA] and other CV death, non-fatal ACS, and non-fatal CVA requiring hospitalization during the observation period) was 6.2%; respective incidences of CV death, non-fatal ACS, and CVA were 0.7%, 4.5%, and 1.7%. Statin, intensive statin, and ezetimibe were prescribed for 93.6%, 8.2%, and 3.9% at visit (V)1 (Day[D]1＋14), and 92.3%, 10.5%, and 11.6% of patients at V5 (D730±30 days), respectively. Mean LDL-C was reduced from first post-ACS measurement (121.3 mg/dL) to V5 (79.8 mg/dL). A limited number of patients achieved LDL-C ＜70 mg/dL from V1–V5 (14.4%–34.6%); those with a greater LDL-C reduction by V1 had a lower probability of MACE, indicating the benefits of early LDL-C reduction post ACS. Conclusions: Guideline-recommended LDL-C target achievement post ACS in Japan is suboptimal, suggesting the need for LLT intensification. Additional analyses by risk stratification of the study population and the benefits of lipid management are planned.

The Biomarker-Based Prediction Rule for Risk Stratification in Patients with Acute Coronary Syndromes: A Development and Validation Study: Results from BIPass Registry

Background: Patients with acute coronary syndromes (ACS), the acute and severe manifestation of coronary artery disease, are highly heterogeneous in their risk for recurrent cardiovascular events. Several biomarkers carry prognostic information for cardiovascular events. However, instruments integrating clinical characteristics and biomarkers to accurately predict the occurrence of cardiovascular events, thus facilitating individualization of ACS care are lacking. Methods: Using data from 4,407 ACS patients enrolled in a prospective and multicenter Chinese cohort, BIomarker-based Prognostic Assessment for Patients with Stable Angina and Acute Coronary Syndromes (BIPass) registry, we developed a risk model to predict the major adverse cardiovascular events (MACE, defined as the composite of cardiac death, myocardial infarction [MI] and ischemic stroke) within 12 months after hospital admission. Validation was performed in 1,409 patients from an independent cohort. Findings: Over 12 months, MACE occurred in 196 patients (incidence rate 5·07 per 100 person- years, 95% CI [4·42-5·81]/100 person-years). Predictors of MACE included N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) biomarkers, and clinical variables of age, hypertension, previous MI, previous stroke, Killip class, and heart rate. The developed BIPass risk model displayed excellent discriminative capability (C statistic 0·82, 95% CI 0·78-0·86) and calibration, outperformed GRACE and TIMI risk scores. Similar discrimination, calibration and clinical decision curves were confirmed in the validation cohort. Cumulative rates for MACE demonstrated good separation in BIPass predicted low, intermediate and high-risk groups in both the development and validation cohorts. The BIPass risk model consistently provided enhanced predictions of MACE over a broad-spectrum of ACS and across clinically important subgroups (i.e. age, diagnosis, coronary revascularization, medications). Interpretation: BIPass risk model integrating clinical variables and biomarkers measured at admission is useful to predict risk of 12-month cardiovascular events in ACS, which offers the potential to identify higher-risk patients as candidates for early aggressive treatments. Trial Registration: NCT04044066 Funding Statement: National Key R＆D Program of China (2017YFC0908700, 2017YFC0908703), National S&T Fundamental Resources Investigation Project (2018FY100600, 2018FY100602), Taishan Pandeng Scholar Program of Shandong Province (tspd20181220), Taishan Young Scholar Program of Shandong Province (tsqn20161065, tsqn201812129). Declaration of Interests: None. Ethics Approval Statement: The BIPass study was approved by the research ethics committee of Qilu Hospital, Shandong University which was accepted by all the collaborating hospitals.

Antiplatelet therapy in patients with myocardial infarction without obstructive coronary artery disease

ObjectiveApproximately 10% of patients with myocardial infarction (MI) have no obstructive coronary artery disease. The prognosis and role of intensified antiplatelet therapy in those patients were evaluated.MethodsWe analysed data from...

Obesity in patients with established coronary artery disease over a 20-year period (1997-2017).

Body mass reduction in overweight and obese people so as to reduce blood pressure, low‑density lipoprotein cholesterol level, and the risk of type 2 diabetes as well as to lower the risk of recurrent cardiovascular events is strongly recommended in current guidelines. To evaluate changes in body mass index (BMI) and waist circumference in patients with established coronary artery disease over a 20‑year period (1997-2017). Consecutive patients younger than 71 years of age and hospitalized for acute coronary syndrome or myocardial revascularization procedures were recruited and interviewed 6 to 18 months after their discharge from hospital. Weight, height, and waist circumference were measured in 1997 to 1998, 1999 to 2000, 2006 to 2007, 2011 to 2013, and 2016 to 2017. The same 5 hospitals took part in the surveys each time. We examined 412 patients in 1997 to 1998 (survey 1), 427 in 1999 to 2000 (survey 2), 422 in 2006 to 2007 (survey 3), 462 in 2011 to 2013 (survey 4), and 272 in 2016 to 2017 (survey 5). The proportion of obese patients was 24.5% in survey 1, 27.2% in survey 2, 34.1% in survey 3, 35.9% in survey 4, and 40.4% in survey 5 (P <0.001). The proportion of patients with central obesity also increased significantly (32.5% in survey 1, 40.5% in survey 2, 51.4% in survey 3, 48.6% in survey 4, and 61.3% in survey 5; P <0.001). BMI increased significantly in men, but not in women, whereas the mean waist circumference increased in both sexes. BMI and waist circumference increased irrespective of age and education. The analysis of 5 multicenter surveys showed a gradual increase in BMI and waist circumference in patients with established coronary artery disease over the course of 2 decades.

Alarmin-activated B cells accelerate murine atherosclerosis after myocardial infarction via plasma cell-immunoglobulin-dependent mechanisms.

Myocardial infarction (MI) accelerates atherosclerosis and greatly increases the risk of recurrent cardiovascular events for many years, in particular, strokes and MIs. Because B cell-derived autoantibodies produced in response to MI also persist for years, we investigated the role of B cells in adaptive immune responses to MI. We used an apolipoprotein-E-deficient (ApoE-/-) mouse model of MI-accelerated atherosclerosis to assess the importance of B cells. One week after inducing MI in atherosclerotic mice, we depleted B cells using an anti-CD20 antibody. This treatment prevented subsequent immunoglobulin G accumulation in plaques and MI-induced accelerated atherosclerosis. In gain of function experiments, we purified spleen B cells from mice 1 week after inducing MI and transferred these cells into atherosclerotic ApoE-/- mice, which greatly increasedimmunoglobulin G (IgG) accumulation in plaque and accelerated atherosclerosis. These B cells expressed many cytokines that promote humoural immunity and in addition, they formed germinal centres within the spleen where they differentiated into antibody-producing plasma cells. Specifically deleting Blimp-1 in B cells, the transcriptional regulator that drives their terminal differentiation into antibody-producing plasma cells prevented MI-accelerated atherosclerosis. Alarmins released from infarcted hearts were responsible for activating B cells via toll-like receptors and deleting MyD88, the canonical adaptor protein for inflammatory signalling downstream of toll-like receptors, prevented B-cell activation and MI-accelerated atherosclerosis. Our data implicate early B-cell activation and autoantibodies as a central cause for accelerated atherosclerosis post-MI and identifies novel therapeutic strategies towards preventing recurrent cardiovascular events such as MI and stroke.

Abstract 16276: Lipoprotein (a) Predicts Recurrent Worse Outcomes in Type 2 Diabetes Mellitus Patients With Prior Cardiovascular Events: A Prospective, Observational Cohort Study

Introduction: Merging studies have reported the association of lipoprotein(a) [Lp(a)] with poor outcomes of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, the prognostic importance of Lp(a) for recurrent cardiovascular events (CVEs) is currently undetermined in patients with T2DM and prior CVEs. Methods: From April 2011 to March 2017, we consecutively recruited 2,284 T2DM patients with prior CVEs. Patients were categorized into low, medium, and high groups by Lp(a) levels and followed up for hard, recurrent CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Caplan-Meier, Cox regression and C-statistic analyses were performed. Results: During 7,613 patient-years’ follow-up, 153 recurrent CVEs occurred. Lp(a) levels were significantly higher in patients with recurrent CVEs than counterparts (20.44 vs. 14.71 mg/dL, p=0.002). Kaplan-Meier analysis revealed that the event-free survival rate was dramatically lower in high and medium Lp(a) groups than that in low group irrespective of HBA1c status (&lt;7.0%; ≥7.0%, both p&lt;0.05). Furthermore, multivariate Cox regression models indicated that Lp(a) was independently associated with high risk of recurrent CVEs [HR(95% CI): 2.049(1.308-3.212)], such data remains in different HBA1c status (HR(95% CI): &lt;7.0%, 2.009(1.051-3.840); ≥7.0%, 2.162(1.148-4.073)). Moreover, the results of C-statistic were significantly improved by 0.029 when added Lp(a) to the Cox model. Conclusions: Our data, for the first time, confirmed that Lp(a) was an independent predictor for recurrent CVEs in T2DM patients with prior CVEs, suggesting that Lp(a) measurement may help to further risk stratification for T2DM patients after they suffered a first CVE.

Discontinuation of Secondary-Prevention Medications Is Common After Stroke or TIA

Antihypertensive, antithrombotic, and lipid-lowering agents are effective at reducing the risk for recurrent cardiovascular events after stroke or

Apparent resistant hypertension and the risk of recurrent cardiovascular events and mortality after a first manifestation of vascular disease

Abstract Background Previous studies have shown that patients with resistant hypertension carry a higher risk of developing cardiovascular disease than patients with non-resistant hypertension. However, little is known about the prognosis of apparent resistant hypertension in patients with symptomatic vascular disease. Purpose The aim of this study was to examine the relation between different stages of hypertension and the risk of recurrent cardiovascular events and mortality in a cohort of hypertensive patients with symptomatic vascular disease. Methods Hypertensive patients (n=7280) with symptomatic vascular disease (cerebrovascular disease, coronary heart disease, peripheral artery disease or abdominal aortic aneurysm) were included from the ongoing SMART cohort between 1996 and 2018. Patients were classified into three groups according to baseline office blood pressure (BP): controlled (BP &amp;lt;140/90 mmHg and a hypertension diagnosis or on 1 to 3 antihypertensive drugs), uncontrolled (BP ≥140/90 mmHg on ≤2 drugs) and apparent resistant (BP ≥140/90 mmHg despite treatment with three or more antihypertensive drugs including a diuretic or treatment with four or more antihypertensive medications irrespective of BP status). Cox proportional hazard models were used to quantify the relation between the different stages of hypertension and the risk of recurrent major adverse cardiovascular events (MACE including stroke, myocardial infarction and vascular death) and death from any cause. Models were adjusted for age, sex, current smoking, body mass index, renal function and diabetes. In addition, survival according to the different stages of hypertension was plotted, taking competing risk of non-vascular mortality into account by using the Fine and Gray method. Results In total 3123 patients (43%) had controlled hypertension, 3354 patients (46%) had uncontrolled hypertension and 803 (11%) had apparent resistant hypertension. A total of 1498 MACE and 1762 deaths occurred in 64,469 person-years (median follow-up of 8.6 years, IQR 4.6–12.7 years). Compared to patients with controlled hypertension patients with apparent resistant hypertension were at increased risk of recurrent MACE (HR 1.32; 95% CI 1.11–1.58) and death from any cause (HR 1.46; 95% CI 1.25–1.72). At the age of 60 years, patients with apparent resistant hypertension after a first cardiovascular event on average had a recurrent cardiovascular event 10 years earlier than patients with controlled or uncontrolled hypertension (Figure 1). Conclusions Irrespective of age at first cardiovascular event, apparent resistant hypertension is related to a higher risk of recurrent vascular events and death from any cause. These findings support the need for greater efforts toward improving blood pressure control and treatment of other cardiovascular risk factors among patients with apparent resistant hypertension. Figure 1 Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): UMC Utrecht

Risk for recurrent cardiovascular events and expected risk reduction with optimal treatment one year after an acute coronary syndrome

Abstract Background According to the latest ESC Guidelines for chronic coronary syndromes (CCS), patients who suffered an acute coronary syndrome (ACS) pass to a chronic stable phase after one year. In these patients the estimated 10-year risk for recurrent cardiovascular (CV) events varies considerably. We estimated this risk and the expected risk reduction after optimal control. Methods We applied the SMART risk score in 211 patients one year after an ACS to estimate the 10-year risk for recurrent CV events (subsequent non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death). We assessed the distribution of the estimated risk and the potential risk reduction that might be achieved with an optimal guideline-directed management of modifiable risk factors (systolic blood pressure, low-density lipoprotein cholesterol, smoking and body mass index). Results In our cohort, the median SMART score was 16% [interquartile range (IQR), 9.5–26]. If all modifiable risk factors met guideline-recommended targets, median SMART risk score would be 9.4% (IQR, 5.9–17.1), with 52% of the patients at a 10-year risk &amp;lt;10%, while 10% and 11% at 20–30% and &amp;gt;30% risk respectively. The total median reducible risk was 4.7% (IQR, 1.7–8.8). Conclusions The SMART score had a wide distribution among patients with CCS. Noteworthy, one out of five patients will remain at a &amp;gt;20% 10-year risk, even with optimal risk factors management, clearly underlining that residual risk is an unmet clinical issue, which demands individualized patient care. Baseline and total residual risk score Funding Acknowledgement Type of funding source: None

Interleukin-1Beta and risk of premature death and MACE in patients with myocardial infarction

Abstract Background Inhibition of the interleukin-1β (IL-1β) innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high sensitivity C-reactive protein (hs-CRP). However, the prognosis value of IL-1β level in acute myocardial infarction patients has never been evaluated. We aim to assess the association between IL-1β level with all-cause mortality in patients with acute ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death. Methods IL-1β concentration was measured among 1398 STEMI patients enrolled in a prospective cohort study. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90-days and one-year using a multivariate-cox proportional regression analysis. Major cardiovascular events (MACE) were also analyzed. Results In a STEMI population, IL-1β concentration measured at admission was independently associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR], 1.43 per 1SD increase; 95% CI, 1.12 to 1.83; p&amp;lt;0.005). The relation was nonlinear, and we identified a threshold of IL-1β &amp;gt;10 pg/mL that was markedly associated with higher mortality rates at 90 days (adjHR: 2.80; 95% CI: 1.63–4.80, p=0.0002) and one-year (adjHR: 1.75; 95% CI: 1.09–2.78, p=0.019), regardless of the hs-CRP concentration. The relationship was even stronger when considering cardiovascular mortality and MACE at 90 days (adjHR: 2.31; 95% CI: 1.30–4.10, p=0.004 and 2.17; 95% CI: 1.24–3.80, p=0.006) and at one year (adjHR: 2.26; 95% CI: 1.31–3.87, p=0.03 and 2.25; 95% CI: 1.33–3.79, p=0.004). Conclusion IL-1β measured at admission in acute MI patients is associated with the risk of mortality and recurrent major cardiovascular events, regardless of the CRP level. A threshold of 10 pg/mL identifies patients at higher risk of events. Survival Funding Acknowledgement Type of funding source: None

Cardiovascular family history increases the risk of disease recurrence after a first myocardial infarction

Abstract Background Despite recent advances in secondary prevention, recurrent cardiovascular events are common after a myocardial infarction (MI). It has been reported that genetic risk scores may predict the risk of recurrent cardiovascular events. Although patient-derived family history is a composite of both genetic and environmental heritability of atherosclerotic cardiovascular disease (ASCVD), it is an easily accessible information compared to genetically based risk models but the association with recurrent events is unknown. Purpose To evaluate whether a register-verified family history of ASCVD is associated with recurrent cardiovascular events (rASCVD) in patients after a first-time MI. Methods We included patients with a first-time MI during 2005 – 2014, registered in the SWEDEHEART SEPHIA registry and without prior ASCVD. Follow-up was available until Dec 31st, 2018. Data on relatives, diagnoses and prescriptions were extracted from national registers. A family history of ASCVD was defined as a register-verified hospitalisation due to MI, angina with coronary revascularization procedures, stroke or cardiovascular death in any parent. Early history was defined as such an event before the age of 55 years in fathers and 65 years in mothers. The association between family history and a composite outcome including recurrent MI, angina requiring acute revascularization, ischaemic stroke and cardiovascular death during follow-up was studied with Cox proportional hazard regression with time from SEPHIA registry completion as underlying time-scale, adjusted for age with splines, gender and year of SEPHIA registry. Regression models were then further adjusted for hypertension, diabetes, smoking and for a subset of patients, LDL-cholesterol (LDL_C) at time of first event. Results Of 25,615 patients, 2.5% and 32.1% had an early and ever-occurring family history of ASCVD, respectively. Patients with early family history were significantly younger than other patients and were more likely to be current smokers and have a higher LDL-C (Median (IQR) 3.5 (1.1) vs 3.3 (1.1) mmol/L). In total, 3,971 (15.5%) patients experienced the outcome. Early family history of ASCVD was significantly associated with rASCVD (Hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.23–1.87), and the effect was sustained when adjusted for cardiovascular risk factors (HR 1.48, 95% CI 1.20–1.83) and LDL-C (HR 1.35, 95% CI 1.04–1.74). Ever-occurring family history was weakly associated with ASCVD (HR 1.09, 95% CI 1.02 – 1.17) and the association remained unchanged with adjustments for risk factors. Conclusions Early family history of cardiovascular disease is a potent risk factor for recurrent cardiovascular events in a secondary prevention setting, independent of traditional risk factors including LDL-C. This is a novel finding and these patients may potentially benefit from intensified secondary preventive measures after a first-time MI. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This work was funded by grants from The Swedish Heart and Lung Association