Established Atherosclerotic Disease Research Articles

Exploring criteria for active surveillance of perioperative myocardial infarction/injury following noncardiac surgery

Abstract Introduction Recent cardiology guidelines on perioperative management of cardiovascular diseases during noncardiac surgery include recommendations concerning perioperative screening for perioperative myocardial infarction/injury (PMI) to improve patient care. However, little evidence exists on the optimal population to be screened. Methods In this post-hoc analysis of our ongoing prospective multicenter observational study BASEL-PMI which included consecutive high-risk patients undergoing major noncardiac surgery, who 1) were ≥45 years with a history of coronary artery disease, peripheral arterial disease, or stroke/TIA, summarized as established atherosclerotic disease (EAD) OR 2) were ≥65 years old. For these two groups, we calculated univariable incidences of PMI stratified by risk factors, surgical specialties, and surgical risk estimates . A Conway-Maxwell Poisson regression model was used to obtain multivariable adjusted incidence rates. Results Between 2014-2018 9290 patients were included, of which 13.3% developed a PMI. The incidence rates of PMI were higher in patients with EAD than in patients without EAD, but in both groups the incidence of PMI was >10%. In both groups, patients with chronic heart failure (CHF, 19 and 27%, respectively) and chronic kidney disease < 30 ml/min (19 and 29%, respectively) were associated with the highest incidences of PMI. In multivariable analysis, high surgical risk classification, anemia, and a metabolic equivalent of task (MET) <4 showed the highest incidence rate of PMI (high-risk surgery: 8.08/100 patients, intermediate-risk surgery 7.63/100 patients, anemia: 6.73/100 patients, MET <4: 6.25/100 patients), while cardiovascular comorbidities were evenly distributed. Conclusions Patients undergoing noncardiac surgery with established EAD or aged >65 years all show an incidence of PMI >10%, hence screening seems warranted in those patients. Established atherosclerotic disease, established CHF, higher risk of surgery, anaemia, and poor MET are associated with high rates of PMI.Poisson adjusted PMI Incidence Rate

Association Between Historical Neighborhood Redlining and Cardiovascular Outcomes Among US Veterans With Atherosclerotic Cardiovascular Diseases

In the 1930s, the government-sponsored Home Owners' Loan Corporation (HOLC) established maps of US neighborhoods that identified mortgage risk (grade A [green] characterizing lowest-risk neighborhoods in the US through mechanisms that transcend traditional risk factors to grade D [red] characterizing highest risk). This practice led to disinvestments and segregation in neighborhoods considered redlined. Very few studies have targeted whether there is an association between redlining and cardiovascular disease. To evaluate whether redlining is associated with adverse cardiovascular outcomes in US veterans. In this longitudinal cohort study, US veterans were followed up (January 1, 2016, to December 31, 2019) for a median of 4 years. Data, including self-reported race and ethnicity, were obtained from Veterans Affairs medical centers across the US on individuals receiving care for established atherosclerotic disease (coronary artery disease, peripheral vascular disease, or stroke). Data analysis was performed in June 2022. Home Owners' Loan Corporation grade of the census tracts of residence. The first occurrence of major adverse cardiovascular events (MACE), comprising myocardial infarction, stroke, major adverse extremity events, and all-cause mortality. The adjusted association between HOLC grade and adverse outcomes was measured using Cox proportional hazards regression. Competing risks were used to model individual nonfatal components of MACE. Of 79 997 patients (mean [SD] age, 74.46 [10.16] years, female, 2.9%; White, 55.7%; Black, 37.3%; and Hispanic, 5.4%), a total of 7% of the individuals resided in HOLC grade A neighborhoods, 20% in B neighborhoods, 42% in C neighborhoods, and 31% in D neighborhoods. Compared with grade A neighborhoods, patients residing in HOLC grade D (redlined) neighborhoods were more likely to be Black or Hispanic with a higher prevalence of diabetes, heart failure, and chronic kidney disease. There were no associations between HOLC and MACE in unadjusted models. After adjustment for demographic factors, compared with grade A neighborhoods, those residing in redlined neighborhoods had an increased risk of MACE (hazard ratio [HR], 1.139; 95% CI, 1.083-1.198; P < .001) and all-cause mortality (HR, 1.129; 95% CI, 1.072-1.190; P < .001). Similarly, veterans residing in redlined neighborhoods had a higher risk of myocardial infarction (HR, 1.148; 95% CI, 1.011-1.303; P < .001) but not stroke (HR, 0.889; 95% CI, 0.584-1.353; P = .58). Hazard ratios were smaller, but remained significant, after adjustment for risk factors and social vulnerability. In this cohort study of US veterans, the findings suggest that those with atherosclerotic cardiovascular disease who reside in historically redlined neighborhoods continue to have a higher prevalence of traditional cardiovascular risk factors and higher cardiovascular risk. Even close to a century after this practice was discontinued, redlining appears to still be adversely associated with adverse cardiovascular events.

2022 Canadian Cardiovascular Society Guideline for Use of GLP-1 Receptor Agonists and SGLT2 Inhibitors for Cardiorenal Risk Reduction in Adults.

This guideline synthesizes clinical trial data supporting the role of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors (SGLT2i) for treatment of heart failure (HF), chronic kidney disease, and for optimizing prevention of cardiorenal morbidity and mortality in patients with type 2 diabetes. It is on the basis of a companion systematic review and meta-analysis guided by a focused set of population, intervention, control, and outcomes (PICO) questions that address priority cardiorenal end points. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system and a modified Delphi process were used. We encourage comprehensive assessment of cardiovascular (CV) patients with routine measurement of estimated glomerular filtration rate, urinary albumin-creatinine ratio, glycosylated hemoglobin (A1c), and documentation of left ventricular ejection fraction (LVEF) when evaluating symptoms of HF. For patients with HF, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy for the reduction of hospitalization for HF when LVEF is > 40% and for the reduction of all-cause and CV mortality, hospitalization for HF, and renal protection when LVEF is ≤ 40%. In patients with albuminuric chronic kidney disease, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy to reduce all-cause and CV mortality, nonfatal myocardial infarction, and hospitalization for HF. We provide recommendations and algorithms for the selection of glucagon-like peptide-1 receptor agonists and SGLT2i for patients with type 2 diabetes and either established atherosclerotic CV disease or risk factors for atherosclerotic CV disease to reduce all-cause and CV mortality, nonfatal stroke, and for the prevention of hospitalization for HF and decline in renal function. We offer practical advice for safe use of these diabetes-associated agents with profound cardiorenal benefits.

Statin Intolerance and Noncompliance: An Empiric Approach

Statin Intolerance and Noncompliance: An Empiric Approach

Determinants and Outcomes of Asymptomatic Intracranial Atherosclerotic Stenosis

BackgroundIntracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive management of risk factors. ObjectivesThis study identified the role of risk factors and risk of vascular events in subjects with asymptomatic ICAS for improved risk stratification. MethodsStroke-free participants in the NOMAS (Northern Manhattan Study), prospectively followed since 1993, underwent a brain magnetic resonance angiogram from 2003 to 2008. The study rated stenosis in 11 brain arteries as: 0: no stenosis; 1: <50% or luminal irregularities; 2: 50%-69%; and 3: ≥70% stenosis or flow gap. The study ascertained vascular events during the post-magnetic resonance imaging (MRI) period. Proportional odds regression quantified the association of pre-MRI exposures, and proportional hazard adjusted models were built to identify the risk of events in the post-MRI period. ResultsThe included sample included 1,211 participants from NOMAS (mean age: 71 ± 9 years; 59% women; 65% Hispanic; 45% had any stenosis). Older age (OR: 1.02 per year; 95% CI: 1.01 to 1.04), hypertension duration (OR: 1.01 per year; 95% CI: 1.00 to 1.02), higher number of glucose-lowering drugs (OR: 1.64 per each medication; 95% CI: 1.24 to 2.15), and high-density lipoprotein (OR: 0.96 per mg/dL; 95% CI: 0.92 to 0.99) were associated with ICAS. The highest event risk was noted among participants with ICAS ≥70% (5.5% annual risk of vascular events; HR: 2.1; 95% CI:1.4 to 3.2; compared with those with no ICAS). ConclusionsICAS is an imaging marker of established atherosclerotic disease in stroke-free subjects, and incidental diagnosis of ICAS should trigger a thorough assessment of vascular health.

Factors associated to serum paraoxonase 1 activity in patients with cardiovascular disease.

Paraoxonase 1 (PON1) is an enzyme that has antioxidant potential, which confers a protective effect against the atherosclerotic process. However, studies associating genetics, dietary patterns and PON1 activity in individuals with cardiovascular disease (CVD) are scarce. Thus, the aim of the current study was to evaluate the influence of dietary factors on serum PON1 in CVD patients. Cross-sectional, sub-study of the BALANCE Program Trial. All patients aged 45 years or older and had evidence of established atherosclerotic disease in the preceding 10 years. Body weight, height, waist circumference, blood pressure, lipid profile and fasting glucose were collected. Food intake was assessed with 24-h dietary recall. Data was analyzed using SAS University Edition and a P value ≤ 0.05 was considered statistically significant. Sample was divided into three groups, according to the PON1 T(-107)C genotype (CC, CT and TT) and serum PON1 activity (Low, Medium, High). There were no genotype differences for major factors. However, the systolic blood pressure was lower for CT individuals (p<0.05). Intake of cholesterol, saturated fatty acids (SFA) and monounsaturated fatty acids (MUFAS) was higher in patients with lower PON1 activity. Lipid ingestion tended to be higher in patients with lower PON1 activity (p=0.08). In the multivariate logistic regression model, SFA intake (P=0.03), genotype (P=0.09), gender (P=0.04), age (P=0.07) and carbohydrate intake (P=0.16) contributed the most to the serum PON1 activity. Based on these findings, nutritional guidance for these patients becomes essential, since dietary components interact with serum PON1 activity more than genotype.

Cardiovascular outcome in patients with high risk cardiovascular events in Nakornping Hospital

Objectives Patients with atherosclerosis are at different levels of elevated risk of ischemic events depending on the specific manifestation of the disease and may have varying degrees of future risk for ischemic events. This study evaluated the incidence of composite cardiovascular outcomes of patients with high risk cardiovascular events in Nakornping Hospital. Methods This prospective observational non-interventional cohort study enrolled patients age 45 years or more who met the inclusion criteria of the Outpatient Department of Medicine, Nakornping Hospital, between January 2008 and December 2009. The follow-up period for each patient was 60 months. The composite cardiovascular outcome of cardiovascular deaths, non-fatal myocardial infarctions, non-fatal strokes and hospitalizations for heart failure was determined. Results Of the 387 patients in the Outpatient Department of Medicine of Nakornping Hospital, 103 were in the established atherosclerotic disease group and 284 were in the multiple risk factors group. The rate of overall composite cardiovascular events (cardiovascular death, non-fatal MI, non-fatal stroke, and hospitalization for heart failure) was 3.83%. The rate was higher in the established atherosclerotic disease group than in the multiple risk factors group 6.79% vs. 1.41% (HR = 14.28; 95% CI, 2.26-90.02, p = 0.005) which was driven by hospitalization for heart failure, but the established atherosclerotic disease group had a lower rate of medical treatment for diabetes than the multiple risk factors group. The rate of receipt of anti-diabetic drugs was statistically significantly lower in the established atherosclerotic disease group than in the multiple risk factors group. Conclusions Patients with established atherosclerotic disease have a higher rate of composite cardiovascular outcomes than patients with multiple risk factors, but they have a lower rate of medical treatment for diabetes.

Dulaglutide and Insulin: How Can the AWARD Studies Help Guide Clinical Practice?

The glucagon-like peptide 1 receptor agonist (GLP-1RA) dulaglutide has many characteristics to recommend it both as a second-line agent and as an alternative to or in combination with insulin. This commentary summarises recent updates to diabetes management guidelines regarding the use of GLP-1RAs such as dulaglutide, both as a second-line agent and as a first-line injectable agent in type 2 diabetes (T2D). It also examines how the Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in Diabetes (AWARD) studies with dulaglutide and insulin may help to guide clinical practice for the use of dulaglutide as an alternative to basal insulin or in combination with insulin.Individualising glucose-lowering therapy is important in patients with T2D, especially given patients’ heterogeneity in terms of age, lifestyle, disease duration, level of hyperglycaemia and comorbidities. Choice of therapy should be guided by clinical considerations (e.g. high risk or existing cardiovascular [CV] disease, heart failure, chronic kidney disease, risk of hypoglycaemia), side effect profile, contraindications, patient preferences and cost. The recently updated American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) guidelines now recommend adding a GLP-1RA with proven CV benefit to metformin in patients with T2D and indicators of high risk or established atherosclerotic CV disease. The AWARD studies demonstrate that dulaglutide provides effective glucose lowering together with sustained weight loss and a low incidence of hypoglycaemia when used as the first injectable option and when used in combination with titrated basal insulin or prandial insulin, providing a valid treatment option across a wide range of patients with T2D, including those with chronic kidney disease.

Incidence and Predictors of Major Adverse Cardiovascular Events in Patients With Established Atherosclerotic Disease or Multiple Risk Factors.

BackgroundThere is a paucity of contemporary data estimating the incidence of major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or multiple risk factors managed in routine practice. We estimated 1‐ and 4‐year incidences of MACE and the association between MACE and vascular beds affected in these patients.Methods and ResultsUsing US IBM MarketScan data from January 1, 2013 to December 31, 2017, we identified patients ≥45 years old with established coronary artery disease, cerebrovascular disease, peripheral artery disease, or the presence of ≥3 risk factors for atherosclerosis during 2013 with a minimum of 4 years of follow‐up. We calculated 1‐ and 4‐year incidences of MACE (cardiovascular death or hospitalization for myocardial infarction or ischemic stroke). A Cox proportional hazards regression model adjusted for age and sex was used to evaluate the association between vascular bed number/location(s) affected and MACE. We identified 1 302 856 patients with established atherosclerotic disease or risk factors for atherosclerosis. Coronary artery disease was present in 16.9% of patients, cerebrovascular disease in 7.6%, peripheral artery disease in 13.6%, and risk factors for atherosclerosis only in 66.0%. The 1‐ and 4‐year incidences of MACE were 1.4% and 6.9%, respectively. At 4 years, MACE was more frequent in patients with atherosclerotic disease in a single (hazard ratio=1.51, 95% CI=1.48–1.55), 2‐(hazard ratio=2.35, 95% CI=2.27–2.44), or all 3 vascular beds (hazard ratio=3.30, 95% CI=2.97–3.68) compared with having risk factors for atherosclerosis.ConclusionsPatients with established atherosclerotic disease or who have multiple risk factors and are treated in contemporary, routine practice carry a substantial risk for MACE at 1‐ and 4‐ years of follow‐up. MACE risk was shown to vary based on the number and location of vascular beds involved.

Mechanisms and Evidence for Heart Failure Benefits from SGLT2 Inhibitors.

To review the clinical trial data and underlying mechanistic principles in support of the robust cardiovascular (CV) benefits, in particular, heart failure (HF) outcomes association with sodium-glucose co-transporter-2 (SGLT2) inhibitors. Several large CV outcome trials in patients with type 2 diabetes mellitus (T2DM) and with either established atherosclerotic CV disease (ASCVD) or at high risk for ASCVD reveal that SGLT2 inhibitors cause reductions in CV and HF endpoints. The reduction in ASCVD appears to be confined to those with established ASCVD on the order of ≈ 14%, as does the mortality benefit-all-cause and CV-related. However, hospitalization for HF are reduced by ≈ 33% and occur regardless of baseline patient characteristics. The unprecedented HF outcomes are theorized to occur via several possible mechanisms and include optimization of conventional ASCVD risk factors, improvement in hemodynamics, prevention of cardiac and renal remodeling, inhibition of hormone dysregulation, use of more efficient metabolic substrates, ion channel inhibition, anti-inflammatory effects, and anti-oxidant effects. Recent evidence has unveiled the irrefutable data that SGLT2 inhibitors reduce CV events in patients with T2DM, with a profound effect on reductions in hospitalization for HF. Though several mechanisms conveying this benefit are suggested, most are based in limited data requiring further validation. Nonetheless, the arrival of SGLT2 inhibitors has ushered in a new era of CV risk reductions therapies.

Role of Sodium-Glucose Cotransporter-2 Inhibition in the Treatment of Adults With HeartFailure.

Diabetes and heart failure (HF) independently contribute to significant cardiovascular (CV) morbidity and mortality. Both are tremendous burdens to health-care systems. Among patients with established HF, diabetes mellitus is one of the most common comorbidities, present in up to 45% of all patients. Although atherosclerotic CV disease outcomes are thought to be the major cause of morbidity and mortality among patients with diabetes, HF death and hospitalization has been recognized as being just as common. However, despite this evidence, HF as an outcome among trials of glucose-lowering therapies has been largely ignored. Now, there are 3 noninferiority CV outcome trials that have demonstrated the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to reduce the risk of HF hospitalizations in patients with type 2 diabetes with CV risk factors and/or established atherosclerotic CV disease. The demonstration of a reduction in HF outcomes seen in these CV outcome trials represents a paradigm shift in the management of patients with type 2 diabetes mellitus and atherosclerotic CV disease or CV risk factors. Whether SGLT-2 inhibitors represent a therapeutic strategy to reduce the risk of CV events among patients with established HF remains to be explored. Furthermore, the benefit of SGLT-2 inhibitors in a population of patients with HF yet without diabetes remains to be demonstrated across multiple trials. This review aims to highlight the clinical trial and real-world evidence regarding the safety and efficacy of SGLT-2 inhibitors among patients with type 2 diabetes mellitus and established HF.

Electrocardiographic predictors of cardiovascular events in patients at high cardiovascular risk: a multicenter study.

BackgroundThere are limited data on the prevalence of electrocardiographic (ECG) abnormalities, and their value for predicting a major adverse cardiovascular event (MACE) in patients at high cardiovascular risk. This study aimed to determine the prevalence of ECG abnormalities in patients at high risk for cardiovascular events, and to identify ECG abnormalities that significantly predict MACE.MethodsPatients aged ≥ 45 years with established atherosclerotic disease (EAD) were consecutively enrolled from the outpatient clinics of the six participating hospitals during April 2011 to March 2014. The following data were collected: demographic data, cardiovascular risk factors, history of cardiovascular event, physical examination, ECG and medications. ECG was analyzed using Minnesota Code criteria. MACE included cardiovascular death, non-fatal myocardial infarction, and hospitalization due to unstable angina or heart failure.ResultsA total of 2009 patients were included, 1048 patients (52.2%) had established EAD, and 961 patients (47.8%) had multiple risk factors (MRF). ECG abnormalities included atrial fibrillation (6.7%), premature ventricular contraction (5.4%), pathological Q-wave (Q/QS) (21.3%), T-wave inversion (20.0%), intraventricular ventricular conduction delay (IVCD) (7.3%), left ventricular hypertrophy (LVH) (12.2%), and AV block (12.5%). MACE occurred in 88 patients (4.4%). Independent predictors of MACE were chronic kidney disease, EAD, and the presence of atrial fibrillation, Q/QS, IVCD or LVH by ECG.ConclusionsA high prevalence of ECG abnormalities was found. The prevalence of ECG abnormalities was high even among those with risk factors without documented cardiovascular disease.

The rate of patients at high risk for cardiovascular disease with an optimal low-density cholesterol level: a multicenter study from Thailand.

BackgroundHypercholesterolemia is a major risk factor for cardiovascular events in patients with established atherosclerotic disease (EAD) and in those with multiple risk factors (MRFs). This study aimed to investigate the rate of optimal low-density lipoprotein (LDL) cholesterol level in a multicenter registry of patients at high risk for cardiovascular events.MethodsA multicenter registry of EAD and MRF patients was conducted. Demographic data, medical history, cardiovascular risk factors, anthropometric data, laboratory data, and medications were recorded and analyzed. We classified patients according to target LDL levels based on recommendation by the European Society of Cardiology (ESC) 2011 into Group 1 which is EAD and diabetes or chronic kidney disease (CKD)–target LDL below 70 mg/dL, and Group 2 which is MRF without diabetes or CKD–target LDL below 100 mg/dL. The rate of optimal LDL level in patients with Group 1 and Group 2 was analyzed and stratified according to the treatment pattern of lipid-lowering medications.ResultsA total of 3100 patients were included. Of those, 51.7% were male. Average age was 65.8 ± 9.7 years. Average LDL level was 96.3 ± 32.6 mg/dL. A vast majority (92.7%) received statin and 9.3% received ezetimibe. Optimal LDL level was achieved in 20.3% of patients in Group 1 (LDL < 70 mg/dL), and in 46.6% in Group 2 (LDL < 100 mg/dL). The overall rate of optimal LDL control was 23% since 89.6% of study population belongs to Group 1. The rate of optimal LDL was not different between high and low potency statin. Factors that were associated with optimal LDL control were older age, the presence of coronary artery disease or peripheral artery disease.ConclusionsThe rates of optimal LDL level were unacceptably low in this study population. As such, a strategy to improve LDL control in high-risk population should be implemented.

Effects of Pharmacological Thermogenic Adipocyte Activation on Metabolism and Atherosclerotic Plaque Regression.

Thermogenic adipocytes burn nutrients in order to produce heat. Upon activation, brown adipose tissue (BAT) clears vast amounts of lipids and glucose from the circulation and thus substantially lowers plasma lipid levels. As a consequence, BAT activation protects from the development of atherosclerosis. However, it is unclear if pharmacologic activation of BAT can be exploited therapeutically to reduce plaque burden in established atherosclerotic disease. Here we study the impact of thermogenic adipose tissues on plaque regression in a mouse model of atherosclerosis. Thermogenic adipocytes in atherosclerotic low-density lipoprotein (LDL) receptor (LDLR)-deficient mice were pharmacologically activated by dietary CL316,243 (CL) treatment for 4 weeks and the outcomes on metabolically active tissues, plasma lipids and atherosclerosis were analyzed. While the chronic activation of thermogenic adipocytes reduced adiposity, increased browning of white adipose tissue (WAT), altered liver gene expression, and reduced plasma triglyceride levels, atherosclerotic plaque burden remained unchanged. Our findings suggest that despite improving adiposity and plasma triglycerides, pharmacologic activation of thermogenic adipocytes is not able to reverse atherosclerosis in LDLR-deficient mice.

Influence of Traditional Cardiovascular Risk Factors on Carotid and Femoral Atherosclerotic Plaque Volume as Measured by Three-Dimensional Ultrasound.

Background: Atherosclerosis is a systemic multifocal disease with a preference for the branching points of the arteries. In this study, we quantitatively measured carotid and femoral plaque volume in subjects with cardiovascular risk factors (CVRF) and/or established atherosclerotic disease using a 3D ultrasound technique. Methods: In this prospective, single-centre study, we included 404 patients (median age 64; 56.9% men) with at least one CVRF or established cardiovascular disease. Plaque volume was measured using 3D ultrasound equipped with an automated software. Results: We found a strong correlation of plaque volume with CVRF and the number of vascular beds involved. The strongest associations with total and femoral plaque volume were noted for smoking, hypertension, age, as well as for the presence of peripheral arterial occlusive disease (p < 0.05). Carotid plaque volume was best predicted by hyperlipidaemia, hypertension, age, as well as the presence of cerebrovascular disease and coronary artery disease (p < 0.05). Conclusion: We conclude that smoking appears to be associated with total and femoral plaque volume, whereas hyperlipidaemia seems to be associated with carotid plaque volume. Measurement of 3D plaque volume is a practical and reproducible technique with the potential to become an additional screening tool in cardiovascular risk stratification.

Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials.

The role of aspirin in the primary prevention setting is continuously evolving. Recent randomized trials have challenged the role of aspirin in the primary prevention setting. Electronic databases were searched for randomized trials that compared aspirin vs. placebo (or control) in subjects without established atherosclerotic disease. The primary efficacy outcome was all-cause mortality, while the primary safety outcome was major bleeding. Summary estimates were reported using a DerSimonian and Laird random effects model. A total of 11 trials with 157248 subjects were included. At a mean follow-up of 6.6 years, aspirin was not associated with a lower incidence of all-cause mortality [risk ratio (RR) 0.98, 95% confidence interval (CI) 0.93-1.02; P = 0.30]; however, aspirin was associated with an increased incidence of major bleeding (RR 1.47, 95% CI 1.31-1.65; P < 0.0001) and intracranial haemorrhage (RR 1.33, 95% CI 1.13-1.58; P = 0.001). A similar effect on all-cause mortality and major bleeding was demonstrated in diabetic and high cardiovascular risk patients (i.e. 10-year risk >7.5%). Aspirin was associated with a lower incidence of myocardial infarction (RR 0.82, 95% CI 0.71-0.94; P = 0.006); however, this outcome was characterized by considerable heterogeneity (I2 = 67%), and this effect was no longer evident upon limiting the analysis to the more recent trials. Trial sequential analysis confirmed the lack of benefit of aspirin for all-cause mortality up to a relative risk reduction of 5%. Among adults without established cardiovascular disease, aspirin was not associated with a reduction in the incidence of all-cause mortality; however, it was associated with an increased incidence of major bleeding. The routine use of aspirin for primary prevention needs to be reconsidered.

Soluble ST2 is a biomarker for cardiovascular mortality related to abnormal glucose metabolism in high-risk subjects.

Inflammation plays a role in the development and progression of type 2 diabetes macroangiopathy. Interleukin 33 (IL-33) drives production of Th2-associated cytokines. The soluble form of suppression of tumorigenicity 2 (sST2) acting as a decoy receptor blocks IL-33 and tones down Th2 inflammatory response. We investigated the role of sST2 as a predictor of CV and all-cause mortality in a cohort of patients affected by established atherosclerotic disease. 399 patients with atherosclerotic disease from the Tor Vergata Atherosclerosis Registry performed follow-up every year by phone interview. The primary endpoint was cardiovascular death and the secondary endpoint was death for any other disease. sST2 plasma levels were significantly increased from normal glucose-tolerant patients to patients with history of type 2 diabetes (p < 0.00001). Levels of sST2 were significantly correlated with fasting plasma glucose (R = 0.16, p = 0.002), HbA1c (R = 0.17, p = 0.002), and HOMA (R = 0.16, p = 0.004). Dividing patients in tertiles of sST2 levels, those belonging to the highest tertile showed an increased rate of all-cause and cardiovascular mortality, (all-cause mortality p = 0.045 and CVD mortality p = 0.02). A multivariate Cox analysis revealed that sST2 increased the risk in cardiovascular mortality per SD by hazard ratio 1.050 (95% CI 1.006-1.097, p = 0.025) after adjustment for age and hs-CRP while it did not significantly change the risk for all-cause mortality. High circulating level of sST2 is associated to increased CVD mortality and markers of metabolic dysfunction in subjects with atherosclerotic disease.

THE HIGH PREVALENCE OF FAMILIAL HYPERCHOLESTEROLEMIA IN A POPULATION OF ASCVD PATIENTS WITH LDL-C ABOVE TARGET: AN ANALYSIS FROM THE REACT REGISTRY

Heterozygous familial hypercholesterolemia (FH) prevalence is 1/250 in the general population and 1/125 in ASCVD patients, yet only a minority of patients are formally diagnosed. FH rises significantly with baseline LDL-cholesterol (LDL-C) levels above 5 mmol/L. Early identification and aggressive lipid-lowering therapy is thought to have substantial benefit on prevention of cardiovascular morbidity and mortality. We used a validated imputation for baseline (untreated) LDL-C levels and determined the prevalence of FH in this group, based on accepted international criteria and a new Canadian definition for FH. We intended to prospectively enroll 1800 patients with either established atherosclerotic CV disease (ASCVD) or FH (diagnosed based on traditional criteria), with LDL-C level >3.0mmol/L despite maximally tolerated statin therapy, as part of a national registry (REACT program-Relating Evidence to Achieve Cholesterol Targets). The sponsor terminated funding prematurely, resulting in 195 enrolled patients. We used a validated imputation for baseline (untreated) LDL-C levels, along with other clinical criteria to determine prevalence of FH, using accepted international criteria and a new Canadian definition for FH. Patients were categorized by enrolling physicians as either ASCVD or FH. There were 109 men and 86 women (76% Caucasian), mean age was 63±12 years. Diabetes (29.7%), hypertension (62.1%), smoking (37.9%) and family history of premature ASCVD (59.5%) were common. Six patients (3%) were diagnosed by enrolling physicians as having FH, the remaining as ASCVD. On-treatment LDL-C was 4.26±0.94mmol/L (mean±SD). Based on the dose and type of statin, +/- ezetimibe, imputed baseline or untreated LDL-C was 7.06±2.94mmol/L. A computerized algorithm was used to determine a diagnosis of FH incorporating additional clinical criteria. Using a cut-point of LDL-C >5.0mmol/L, 140/195(72%) of patients had severe hypercholesterolemia, the threshold for considering a diagnosis of FH in adults. Using the Simon-Broome criteria, 47/140(34%) had definite or 24/140(17%) probable FH, and using the Dutch Lipid Clinic Network 48/140(34%) had definite, 5/140(4%) probable or 80/140(57%) possible FH. Results mirror the new Canadian FH definition with 48/140(34%) definite or 13/140(9%) probable FH. This REACT analysis reveals a substantial proportion of ASCVD patients whose LDL-C levels remain above target in fact have probable or definite FH. Appropriate diagnosis of FH in these patients not only guides aggressive therapy, but has important implications for cascade screening and prevention in first degree relatives. Use of an imputed LDL-C in statin treated patients, and simplified tools for FH diagnosis should enable clinicians to more easily identify FH patients in their practices.

Cardiac Rehabilitation in Patients with Established Atherosclerotic Vascular Disease: New Directions in the Era of Value-Based Healthcare.

Exercise-based cardiac rehabilitation (CR) is associated with significant improvements in coronary disease outcomes, but has been underutilized. However, new developments within the field, some spurred by healthcare reform and the transition to more accountable and coordinated care, offer hope for closing the large CR treatment gap. This review presents new CR-related research, policy, and analyses, and discusses how evolving eligibility criteria, referral processes, performance measures, care models, and delivery and payment options could increase CR utilization over the next decade and enable this life-saving secondary prevention intervention to thrive in the era of value-based health care.

Treatment: special conditions: Orthostatic hypotension

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive management of risk factors.This study identified the role of risk factors and risk of vascular events in subjects with asymptomatic ICAS for improved risk stratification.Stroke-free participants in the NOMAS (Northern Manhattan Study), prospectively followed since 1993, underwent a brain magnetic resonance angiogram from 2003 to 2008. The study rated stenosis in 11 brain arteries as: 0: no stenosis; 1: <50% or luminal irregularities; 2: 50%-69%; and 3: ≥70% stenosis or flow gap. The study ascertained vascular events during the post-magnetic resonance imaging (MRI) period. Proportional odds regression quantified the association of pre-MRI exposures, and proportional hazard adjusted models were built to identify the risk of events in the post-MRI period.The included sample included 1,211 participants from NOMAS (mean age: 71 ± 9 years; 59% women; 65% Hispanic; 45% had any stenosis). Older age (OR: 1.02 per year; 95% CI: 1.01 to 1.04), hypertension duration (OR: 1.01 per year; 95% CI: 1.00 to 1.02), higher number of glucose-lowering drugs (OR: 1.64 per each medication; 95% CI: 1.24 to 2.15), and high-density lipoprotein (OR: 0.96 per mg/dL; 95% CI: 0.92 to 0.99) were associated with ICAS. The highest event risk was noted among participants with ICAS ≥70% (5.5% annual risk of vascular events; HR: 2.1; 95% CI:1.4 to 3.2; compared with those with no ICAS).ICAS is an imaging marker of established atherosclerotic disease in stroke-free subjects, and incidental diagnosis of ICAS should trigger a thorough assessment of vascular health.