Risk Of Future Cardiovascular Events Research Articles

Hydroxychloroquine as a Preventive and Therapeutic Option in Preeclampsia - a Literature Review.

Preeclampsia is one of the most feared complications of pregnancy and puerperium and represents a serious threat to mother and child. In addition, a history of preeclampsia increases the risk of future cardiovascular events. New diagnostic and therapeutic approaches are needed. New therapeutic options are currently being discussed, one of which is the administration of hydroxychloroquine. It is an antimalarial drug which is also used to treat rheumatological disease and its use in pregnancy is considered safe. A reduced incidence of preeclampsia in patients with selected rheumatological disorders after administration of hydroxychloroquine has already been shown; however, the case numbers are very low. Neither the full pathogenesis of preeclampsia nor the exact modes of action of hydroxychloroquine have been completely elucidated, but there are several common features which make hydroxychloroquine a promising option for the prevention and treatment of preeclampsia. Further research, especially prospective, randomized controlled trials, is needed to prove its efficacy. This review discusses the pathogenesis of preeclampsia and gives an overview of new options for its prevention and treatment, including the administration of hydroxychloroquine in pregnancy.

The Relationship Between Coronary Calcification And The Natural History Of Coronary Artery Disease

Introduction: Coronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and increases in response to medical therapy. The aim of the current study is to explore the impact of plaque calcification at a lesion and patient level on the natural history of coronary artery disease.

P1252ASSOCIATIONS OF SERUM SCLEROSTIN AND DKK-1 PROTEIN WITH FUTURE CARDIOVASCULAR EVENTS AND MORTALITY IN HEMODIALYSIS PATIENTS; A PROSPECTIVE COHORT STUDY

Abstract Background and Aims Sclerostin and Dickkopf-1 (Dkk-1) protein are inhibitors of the canonical Wnt/β-catenin bone pathway. Sclerostin but not Dkk-1 is associated with increased arterial stiffness. This study examined the prognostic significance of serum sclerostin and Dickkopf-related protein-1 (Dkk-1) levels for cardiovascular outcomes and mortality in hemodialysis patients. Method Serum sclerostin and Dkk-1 levels were measured with ELISA in 80 hemodialysis patients that were followed-up for a median of 45 months. Several factors that could interfere in the association of sclerostin and Dkk-1 with outcomes (including carotid-femoral pulse-wave-velocity (PWV), parathyroid hormone, calcium-phospate product and others) were assessed at baseline The primary end-point was a combination of all-cause death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, hospitalization for decompensated heart failure and new-onset atrial fibrillation. Secondary end-points included cardiovascular and all-cause mortality. Results Cumulative freedom from the primary endpoint was significantly lower for higher tertiles of sclerostin (77.8%, 69.2%, and 40.7% for tertiles 1 to 3 respectively; log-rank-p=0.004). The corresponding risk for the primary outcome was gradually increasing for higher tertiles of sclerostin (Tertile 3: HR: 3.847, 95%CI: 1.502-9.851). No significant association was evident between sclerostin and all-cause mortality, whereas higher sclerostin levels presented a trend towards higher risk for cardiovascular mortality. Dkk-1 levels exhibited no association with the risk of the primary or the secondary endpoints. In stepwise Cox regression modeled analysis, sclerostin levels were associated with the primary outcome, independently of PTH, calcium-phosphate product, serum albumin, CRP and PWV levels (HR: 2.921, 95%CI: 1.401–6.090; p=0.004). Conclusion High serum sclerostin levels are associated with lower cumulative freedom and higher risk for a composite cardiovascular endpoint but not for all-cause mortality. Dkk-1 protein exhibited no association with the future risk of cardiovascular events.

404-P: Cardiovascular Risk Scoring and Stratification in Patients with Type 2 Diabetes Enrolled in a Medicare Advantage Plan

Current tools to identify patients at risk for cardiovascular (CV) disease or events are variable, limiting their utility and generalizability. The purpose of this study was to develop a predictive model to identify patients with type 2 diabetes (T2D) who are ≥65 years of age, enrolled in a Medicare Advantage Prescription Drug (MAPD) plan and at risk for future CV events. This retrospective cohort study used administrative claims, laboratory and enrollment data from 1/2011-12/2018. Patients with T2D were identified from 1/2012-12/2013 using diagnosis codes and/or claims for antihyperglycemic medications. The dependent variable was the first composite CV event defined as ≥1 inpatient hospitalization for myocardial infarction, ischemic stroke, unstable angina, or heart failure or any evidence of revascularization. Independent variables for the prediction survival model included baseline demographic and clinical characteristics prognostic for the dependent variable. C-statistic, accuracy, sensitivity, and specificity were used to assess model performance. Risk ranking was conducted, whereby patients were classified as low, medium or at high risk of an event based on probability distribution derived cut-points. A total of 362,791 patients with T2D were identified. The proportion of patients with ≥1 CV event was 18.0% up to 5 years after T2D identification. The final model included 42 demographic and clinical variables. The C-statistic was 0.68, and accuracy, sensitivity and specificity were 0.63. Results were consistent across the training, test and holdout datasets suggesting internal validity. Up to 5 years after identification, 11% of patients classified as low, 27% as medium, and 51% as high risk had a future CV event. A predictive model for composite CV events utilizing administrative claims to identify and risk stratify patients may be used to scale focused interventions to high-risk T2D patients in a MAPD population to prevent future CVD events. Disclosure J.D. Hayden: Employee; Self; Humana. P. Pimple: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Employee; Spouse/Partner; CVS Caremark. R. Luthra: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. T.G. Prewitt: None. V. Chiguluri: None. M. Kattan: Consultant; Self; GlaxoSmithKline plc. Research Support; Self; Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Inc. R. Harvey: None. A.M. Goss: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. E.O. Caplan: Employee; Self; Humana. Funding Boehringer Ingelheim; Humana

Additional prognostic value of electrocardiographic left ventricular hypertrophy in traditional cardiovascular risk assessments in chronic kidney disease.

Left ventricular hypertrophy (LVH) is a common predictor of the cardiovascular prognosis in chronic kidney disease (CKD). However, whether or not electrocardiography-derived LVH (ECG-LVH) has prognostic value in patients with various degrees of CKD and improves the cardiovascular risk stratification based on traditional risk factors remains unclear. A total of 7206 participants at least 40 years of age who were free from cardiovascular events in a general population were followed for the incidence of cardiovascular events. CKD was confirmed by either the presence of a reduced estimated glomerular filtration rate (eGFR) (<60 ml/min per 1.73 m) or albuminuria, defined as a urinary albumin-to-creatinine ratio (UACR) of at least 30 mg/g Cr. A total of 1886 (26.2%) had CKD, of which 1471 (78.0%) had a preserved eGFR (CKD stage 1-2). After an average 11.3 years of follow-up, the adjusted hazard ratio for the incidence of cardiovascular events significantly increased for ECG-LVH according to the Sokolow--Lyon voltage, Cornell voltage, or Cornell voltage product among participants with CKD (hazard ratio 1.47, P = 0.002), in contrast to those without CKD (hazard ratio 1.15, P = 0.210). The inclusion of any ECG-LVH parameters improved the accuracy of reclassification in any risk prediction model based on the eGFR, UACR, or Framingham 10-year risk score in the CKD participants (net reclassification improvement = 0.13-0.32, all P values <0.040). In patients with CKD stage 1-5, ECG-LVH is useful for predicting the risk of future cardiovascular events and adds prognostic information to traditional cardiovascular risk assessments.

Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling and degradation of extracellular matrix (ECM) proteins. MMPs may modulate various cellular and signaling pathways in atherosclerosis responsible for progression and rupture of atherosclerotic plaques. The effect of MMPs polymorphisms and the expression of MMPs in both the atherosclerotic plaque and plasma was shown. They are independent predictors of atherosclerotic plaque instability in stable coronary heart disease (CHD) patients. Increased levels of MMPs in patients with advanced cardiovascular disease (CAD) and acute coronary syndrome (ACS) was associated with future risk of cardiovascular events. These data confirm that MMPs may be biomarkers in plaque instability as they target in potential drug therapies for atherosclerosis. They provide important prognostic information, independent of traditional risk factors, and may turn out to be useful in improving risk stratification.

Hypertension in children.

Hypertension is a common finding in children, and increases the risk for future cardiovascular events. This review focuses on recent advances in pediatric hypertension research including changes in hypertension guidelines, epidemiology, predictors of hypertension, blood pressure (BP) measurement, effects on target organs, and treatment of hypertension. Changes in the 2017 hypertension guidelines by the American Academy of Pediatrics (AAP) have resulted in increased prevalence of elevated BP and hypertension in the United States, and there is no international consensus on these changes. Despite rising pediatric overweight and obesity in China, hypertension prevalence is stable, suggesting multifactorial effects on childhood BP. Maternal diabetes and exposure to particulate matter are associated with higher childhood BP, and body size in infancy and early childhood is a determinant of adult high BP. Children with elevated BP have evidence of target organ damage with altered retinal vasculature and pulse wave velocity parameters compared to normotensive patients. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be the best antihypertensive medications for the pediatric population even for African-American patients. Research continues to illuminate contributors to pediatric hypertension and demonstrates opportunities for further study on the effects of hypertension and its management in children.

Impact of smoking on cardiovascular outcomes in patients with stable coronary artery disease.

Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the 'smoker's paradox' suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease. The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers. Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p < 0.0001). There were more men among current or former smokers compared with never-smokers. Compared with never-smokers, both current and former smokers were at higher risk of all-cause death (hazard ratio = 1.96 and 1.37) and cardiovascular death (hazard ratio = 1.92 and 1.38) within five years (all p < 0.05). Similarly graded and increased risks were present for myocardial infarction and the composite of cardiovascular death, myocardial infarction and stroke (all p < 0.05). In contrast to the 'smoker's paradox', current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564).

10-year risk for cardiovascular diseases using WHO prediction chart: findings from the civil servants in South-western Nigeria

BackgroundGlobally, cardiovascular diseases (CVDs) have continued to ravage the human existence through the premature deaths of its workforce. Despite this burden, many studies in Nigeria have focused on determining the prevalence of risk factors which alone are insufficient to assess the risk of future cardiovascular events. Therefore, we determined the pattern and predictors of 10-year risk for CVDs in South-western Nigeria.MethodsWe conducted a cross-sectional study among workers at the local government areas (LGAs) of Oyo State. Using a multi-stage sampling technique, we recruited 260 respondents from the LGA secretariats. A pre-tested, interviewer-administered questionnaire was administered to obtain information on the socio-demographics and behavioural attributes. Lipid analysis, anthropometric, blood pressure, fasting blood glucose measurements were done using standard protocols. The respondents’ CVD risk was assessed using WHO prediction chart. Data were analyzed using IBM SPSS version 25; bivariate analysis was done using Chi-square and binary logistic regression was used to identify the predictors of 10-year risk for CVDs at 5% level of significance.ResultsThe mean age of respondents was 46.0 + 6.7 years. The proportion of respondents with good knowledge of risk factors was 57.7%. The prevalence of CVD risk factors were as follows: systolic hypertension (29.6%), visceral obesity (35.8%), diabetes mellitus (18.8%), smoking (5.8%), elevated total cholesterol (55.4%) and physical inactivity (84.6%). The proportion of respondents with low, moderate and high risk of developing CVDs within 10 years was 76.9, 8.5 and 14.6% respectively. Respondents with age ≥ 40 years (aOR = 2.6, 95% CI = 1.3–8.5), management cadre (aOR = 3.8, 95% CI = 1.6–9.6), obesity (aOR = 4.8, 95% CI = 1.2–120), abnormal waist circumference (aOR = 2.8, 95% CI = 1.3–5.2) and physical inactivity (aOR = 2.4, 95% CI = 1.2–4.7) were associated with the higher likelihood of developing CVDs.ConclusionAbout one-sixth of the respondents had high risk of developing CVDs within the next 10 years and it is likely that it will reduce the productivity of the State. Lifestyle modification and early detection of risk factors through regular screening programmes for those with high CVD risk is therefore recommended.

Peptide hormones and risk for future cardiovascular events among prediabetics: a 20-year follow-up in the OPERA study

Background: Prediabetes has proven to have many unfavourable impacts on the cardiovascular system.Methods: The OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study included 1045 middle-aged subjects followed from the years 1990–1993 to 2014. The focus was on peptide hormones.Results: Plasma resistin levels were higher among prediabetics (p = .001), particularly impaired glucose tolerance (IGT) (p < .001), but not impaired fasting glucose (IFG) patients than among normal glucose tolerance (NGT) or diabetes groups. Diabetics showed lower resistin levels than IGT subjects (p < .001). IGT or diabetes groups showed lower adiponectin and higher leptin levels compared to the NGT group (p < .001). The IFG group had the highest blood pressure and left ventricular mass index, even higher than the diabetic group. Diabetics had the highest, prediabetics (IFG + IGT) intermediate and NGT the lowest risk for CVD events during follow-up (p < .001). Among prediabetics, high plasma ghrelin was an independent predictor of CVD events (p < .05) in the Cox regression analysis although it did not significantly improve either classification or discrimination of the patients.Conclusions: Among glucose tolerance groups, patients with IGT had the highest resistin, but equally high leptin and low adiponectin levels as diabetics. Among prediabetics, ghrelin seems to predict independently cardiovascular events in the long term.KEY MESSAGEAmong glucose tolerance groups, patients with IGT had the highest resistin, but equally high leptin and low adiponectin levels as diabetics.Among prediabetics, ghrelin seems to predict independently cardiovascular events in the long term.

Electrocardiographic Left Atrial Abnormality and B-Type Natriuretic Peptide in a General Japanese Population: NIPPON DATA2010.

Aims: P-wave terminal force in lead V1 (PTFV1) is an electrocardiogram marker of increased left atrial pressure and may be a noninvasive and early detectable marker for future cardiovascular events in the general population compared to serum B-type natriuretic peptide (BNP) concentration. The clinical significance of PTFV1 in the contemporary general population is an area of unmet need. We aimed to demonstrate the correlation between PTFV1 and BNP concentrations in a contemporary representative Japanese population.Methods: Among 2,898 adult men and women from 300 randomly selected districts throughout Japan (NIPPON DATA2010), we analyzed 2,556 participants without cardiovascular disease (stroke, myocardial infarction, and atrial fibrillation). Elevated BNP was defined as a value of ≥ 20 pg/mL based on the definition from the Japanese Circulation Society guidelines.Results: In total, 125 (4.9%) participants had PTFV1. Participants with PTFV1 were older with a higher prevalence of hypertension, major electrocardiographic findings, and elevated BNP concentrations (13.5 [6.9, 22.8] versus 7.8 [4.4, 14.5] pg/mL; P < 0.001). After adjustment for confounders, PTFV1 was correlated with elevated BNP (odds ratio, 1.66; 95% confidence interval, 1.05–2.62; P = 0.030). This correlation was consistent among various subgroups and was particularly evident in those aged < 65 years or those without a history of hypertension.Conclusions: In the contemporary general population cohort, PTFV1 was independently related to high BNP concentration. PTFV1 may be an alternative marker to BNP in identifying individuals at a higher risk of future cardiovascular events in the East Asian population.

Rationale and Best Practices for Pediatric Cardiology Prevention Programs

Atherosclerotic cardiovascular diseases are the most common cause of death in North America, and a significant number of children have conditions such as inherited dyslipidemias, overweight/obesity, and hypertension, placing them at increased risk for future cardiovascular events and other comorbidities. Training in cardiovascular prevention is an important tool to help pediatric cardiologists address these issues in children. We describe a model for training pediatric cardiologists in primary and secondary prevention strategies. A multidisciplinary team approach is needed for robust training in dyslipidemias, hypertension, insulin resistance and type 2 diabetes mellitus, and other obesity-related comorbidities. Research is a significant component of training and necessary for translating science into practice. Ongoing education is also necessary, and certification is available through associations such as the National Lipid Association, the American Diabetes Association, The Obesity Society, and the American Hypertension Specialist Certification Program. Knowledge of primordial, primary, and secondary cardiovascular prevention strategies is essential for pediatric cardiologists to accomplish the goal of helping children lead healthier lives long into adulthood.

SUN-101 PREVALENCE AND CORRELATES OF CARDIOVASCULAR CALCIFICATION AND ITS PROGNOSTIC EFFECTS AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE: RESULTS FROM THE C-STRIDE STUDY

Cardiovascular calcification is highly prevalent in patients with chronic kidney disease (CKD) and is predictive of cardiovascular disease (CVD). To date, most studies have focused on Abdominal aortic calcification (AAC) and cardiac valve calcification (CVC) found in dialysis patients. However, information regarding AAC and CVC in non-dialysis CKD patients is limited. We hypothesized that there is a close association between vascular calcification and the prognosis of non-dialysis CKD patients. To test this hypothesis, we conducted a multicenter prospective study to identify the characteristics and risk factors associated with cardiovascular calcification, and its relationship to prognosis, in patients with CKD stages 1 to 4. The C-STRIDE is an ongoing multicenter prospective study lead by the Peking University First Hospital that includes 39 clinical centers located in 28 cities in 22 provinces of China. It strictly adhered to the Helsinki declaration, and all participants signed written informed consent. Cardiovascular calcification was evaluated at baseline by lateral abdominal radiography to detect aortic calcifications, and by echocardiogram to detect valvular calcifications, respectively. We prospectively followed up over more than five years with 3168 CKD patients in the C-STRIDE study. Demographic and laboratory data were collected and analyzed. Among 3168 patients from the C-STRIDE study, a subgroup of 2235 patientswas selected to undergolateral abdominal radiography and a second subgroup of 2756 patients was selected toundergoechocardiography. AAC was present in 206 patients (9.22%) and CVC was present in 163 patients (5.91%). Age, gender, history of CVD, smoking, hypertension, diabetes, levels of hemoglobin, low-density lipoprotein cholesterol and uric acid were associated with presence of AAC, while only age, history of CVD, levels of serum albumin and low-density lipoprotein cholesterol were associated with presence of CVC (all p-values<0.05) (Table 1 & 2). Survival analyses showed that cardiovascular events and all-cause mortality were significantly greater in patients with AAC or with CVC (all p-values for log-rank tests<0.05) (Table 3 & 4). However, there is no significant associations between presence of AAC or CVC and the outcomes in the multivariable Cox regression analysis after adjustment for age and sex. Demographic and traditional cardiovascular risk factors were associated with cardiovascular calcification, especially AAC. However, the presence of cardiovascular calcification cannot predict the future risk of cardiovascular events in the current study.

Association between perivascular inflammation and downstream myocardial perfusion in patients with suspected coronary artery disease.

To investigate the association between pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation derived from coronary computed tomography angiography (CTA) and coronary flow reserve (CFR) by positron emission tomography (PET) in patients with suspected coronary artery disease (CAD). PCAT CT attenuation was measured in proximal segments of all major epicardial coronary vessels of 105 patients with suspected CAD. We evaluated the relationship between PCAT CT attenuation and other quantitative/qualitative CT-derived anatomic parameters with CFR by PET. Overall, the mean age was 60 ± 12 years and 93% had intermediate pre-test probability of obstructive CAD. Obstructive CAD (≥50% stenosis) was detected in 37 (35.2%) patients and impaired CFR (<2.0) in 32 (30.5%) patients. On a per-vessel analysis (315 vessels), obstructive CAD, non-calcified plaque volume, and PCAT CT attenuation were independently associated with CFR. In patients with coronary calcium score (CCS) <100, those with high-PCAT CT attenuation presented significantly lower CFR values than those with low-PCAT CT attenuation (2.47 ± 0.95 vs. 3.13 ± 0.89, P = 0.003). Among those without obstructive CAD, CFR was significantly lower in patients with high-PCAT CT attenuation (2.51 ± 0.95 vs. 3.02 ± 0.84, P = 0.021). Coronary perivascular inflammation by CTA was independently associated with downstream myocardial perfusion by PET. In patients with low CCS or without obstructive CAD, CFR was lower in the presence of higher perivascular inflammation. PCAT CT attenuation might help identifying myocardial ischaemia particularly among patients who are traditionally considered non-high risk for future cardiovascular events.

Early Systolic Lengthening in Patients With ST-Segment-Elevation Myocardial Infarction: A Novel Predictor of Cardiovascular Events.

BackgroundEarly systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force. We sought to evaluate the prognostic potential of ESL in patients with ST‐segment–elevation myocardial infarction treated with primary percutaneous coronary intervention.Methods and ResultsWe prospectively enrolled 373 patients with ST‐segment–elevation myocardial infarction treated with primary percutaneous coronary intervention. All patients underwent a speckle tracking echocardiographic examination a median of 2 days (interquartile range, 1–3 days) after the percutaneous coronary intervention. We assessed a novel viability index, the ESL index, defined as follows: [−100×(peak positive systolic strain/peak negative strain in cardiac cycle)]. We also calculated ESL duration, defined as time from onset of QRS complex on the ECG to time of peak positive systolic strain. Both parameters were averaged from 18 myocardial segments. During a median follow‐up of 5.3 years (interquartile range, 2.5–6.0 years), 145 (39%) experienced major adverse cardiovascular events, a composite of incident heart failure, new myocardial infarction, and all‐cause mortality. The ESL index and ESL duration were significantly increased in culprit lesion areas (6.7±6.2% versus 5.0±4.1% and 43±33 ms versus 33±24 ms, respectively; P<0.001 for both). In Cox proportional hazard models, the ESL index (hazard ratio, 1.27 per 1% increase; 95% CI, 1.13–1.43; P<0.001) and ESL duration (hazard ratio, 1.49 per 1‐ms increase; 95% CI, 1.15–1.92; P=0.002) yielded prognostic information on major adverse cardiovascular events. Both associations remained significant after adjusting for clinical, echocardiographic, and invasive confounders.ConclusionsAssessment of ESL after primary percutaneous coronary intervention in patients with ST‐segment–elevation myocardial infarction yields independent and significant prognostic information on the future risk of cardiovascular events.

Estimation of the increased risk associated with recurrent events or polyvascular atherosclerotic cardiovascular disease in the United Kingdom.

The aims of this study were to re-estimate the international REduction of Atherothrombosis for Continued Health (REACH) risk equation using United Kingdom data and to distinguish different relative hazards for specific atherosclerotic cardiovascular disease event histories. Patients in the UK Clinical Research Practice Datalink (CPRD) were included as of 1 January 2005 if they were 40 years or older, had 2 or more years of prior data, received one or more moderate or high-intensity statin in the previous year, and had a history of myocardial infarction, ischemic stroke, or other atherosclerotic cardiovascular disease. Patients were followed until a composite endpoint of myocardial infarction, ischemic stroke or cardiovascular death, loss to follow-up, or end of observation. We re-estimated the REACH risk equation hazard ratios (HRs) using CPRD data (re-estimated REACH model). Our event history model replaced the REACH vascular bed variables with more specific event histories. There were 60,838 patients with 5.25 years of mean follow-up. In the validation model, HRs were in the same direction, and generally greater than REACH. In the event history model, HRs compared to other atherosclerotic cardiovascular disease alone included: recurrent myocardial infarction (HR 1.19, 95% confidence interval (CI) 1.05-1.34), recurrent ischemic stroke (HR 1.36, 95% CI 1.03-1.80), myocardial infarction and other atherosclerotic cardiovascular disease (HR 1.31, 95% CI 1.23-1.38), ischemic stroke and other atherosclerotic cardiovascular disease (HR 1.40, 95% CI 1.23-1.60), myocardial infarction and ischemic stroke (HR 1.94, 95% CI 1.23-3.04), and myocardial infarction, ischemic stroke and other atherosclerotic cardiovascular disease (HR 1.93, 95% CI 1.47-2.54). A detailed cardiovascular event history may be useful for estimating the relative risk of future cardiovascular events.

Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

BackgroundIndividuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778).MethodsIn DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies.ResultsThis analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls.ConclusionsAmong individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated.Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015

Long-term Prognostic Value of Estimated Plasma Volume in Heart Failure with Preserved Ejection Fraction

Plasma volume, estimated by several indirect methods, has been viewed as a biological surrogate for intravascular fluid status. The clinical implication of estimated plasma volume status (ePVS) for long term outcomes in heart failure with preserved ejection fraction (HFpEF) remains unclear. We investigate the prognostic value of ePVS calculated by Strauss formula and its association with cardiovascular events and mortality in a prospective HFpEF cohort. There were 449 individuals met the inclusion criteria of our cohort. Estimated plasma volume variation (ΔePVS) and its instantaneous derivatives were calculated by the Strauss formula. Our study endpoints were events of heart failure hospitalization and mortality. Kaplan–Meier estimates and Cox regression analysis were applied to determine the power of ΔePVS and baseline ePVS in predicting long term cardiovascular outcomes. Both baseline ePVS and ΔePVS were independent predictors of heart failure hospitalization and mortality. Kaplan-Meier estimates of these outcomes stratified by optimal cut-off value showed that HFpEF individuals with higher baseline ePVS and ΔePVS were associated with elevated risk of composite endpoint of heart failure hospitalization and mortality. This study demonstrated the prognostic value of a novel biological surrogate, instantaneous derivatives ePVS, in predicting long term cardiovascular outcomes in HFpEF population. Monitoring instantaneous plasma volume may assist in identifying patients at high risk for future cardiovascular events. Further prospective studies validating the role of ePVS in predicting long-term prognosis in patients with HFpEF are warranted.

5 Conservative treatment for PAD - Risk factor management.

5 Conservative treatment for PAD - Risk factor management.

1270Early systolic lengthening in patients with ST-segment elevation myocardial infarction: a novel predictor of cardiovascular events

Abstract Background Early systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force. We sought to evaluate the prognostic potential of ESL in patients with ST-segment elevated myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Methods We prospectively enrolled 372 patients with STEMI who were treated with primary PCI. All patients underwent a speckle tracking echocardiographic examination with a median of 2 days (interquartile range 1, 3 days) after the PCI. We assessed a novel viability index, the ESL index, defined as: (100 x [peak positive systolic strain/peak negative global strain]), obtained as the average value from all 18 segments. We also calculated ESL duration from 18 segments, defined as time from onset of QRS complex on the electrocardiogram to time to peak of positive systolic strain. Results During a median follow-up time of 5.3 years (interquartile range 2.5, 6.0), 145 (39%) experienced major adverse cardiovascular events (MACEs), which was a composite of incident heart failure, new myocardial infarction and all-cause mortality. The ESL index and ESL duration were significantly increased in culprit lesion areas (6.7±6.2% vs. 5.0±4.1% and 43±33ms vs. 33±24ms, P&lt;0.001 for both). In Cox proportional hazards models the ESL index (HR 1.27 per 1% increase, 95% CI 1.13–1.43, P&lt;0.001, Fig A) and ESL duration (HR 1.49 per 1ms increase, 95% CI 1.15–1.92, P=0.002, Fig B) yielded prognostic information on MACE. Both associations remained significant after adjusting for clinical (age, sex, hypertension, heart rate), echocardiographic (LVMI, E/e', WMSI, LVEF, postsystolic index) and invasive (postprocedural TIMI flow, TnI) confounders. Additionally, tertiles of the ESL index and ESL duration yielded significant prognostic information on MACE (Fig C-D). ESL index and ESL duration and MACE Conclusions Assessment of ESL following primary PCI in patients with STEMI yields independent and significant prognostic information on the future risk of cardiovascular events.