Intensive Risk Factor Management Research Articles

Is 'Cardiopulmonary' the New 'Cardiometabolic'? Making a Case for Systems Change in COPD.

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) have a syndemic relationship with shared risk factors and complex interplay between genetic, environmental, socioeconomic, and pathophysiological mechanisms. CVD is among the most common comorbidities in patients with COPD and vice versa. Patients with COPD, irrespective of their disease severity, are at increased risk of CVD morbidity and mortality, driven in part by COPD exacerbations. Despite these known interrelationships, CVD is underestimated and undertreated in patients with COPD. Similarly, COPD is an independent risk-enhancing factor for adverse cardiovascular (CV) events, yet it is not incorporated into current CV risk assessment tools, leading to under-recognition and undertreatment. There is a pressing need for systems change in COPD management to move beyond symptom control towards a comprehensive cardiopulmonary disease paradigm with proactive prevention of exacerbations and adverse cardiopulmonary outcomes and mortality. However, there is a dearth of evidence defining optimal cardiopulmonary care pathways. Fortunately, there is a precedent to support systems-level change in the field of diabetes, which evolved from glycemic control to comprehensive multi-organ risk assessment and management. Key elements included integrated multidisciplinary care, intensive risk factor management, coordination between primary and specialist care, care pathways and protocols, education and self management, and disease-modifying therapies. This commentary article draws parallels between the cardiometabolic and cardiopulmonary paradigms and makes a case for systems change towards multidisciplinary, integrated cardiopulmonary care, using the evolution in diabetes care as a potential framework.

Genetics and Pathophysiological Mechanisms of Lipoprotein(a)-Associated Cardiovascular Risk.

Elevated lipoprotein(a) is a genetically transmitted codominant trait that is an independent risk driver for cardiovascular disease. Lipoprotein(a) concentration is heavily influenced by genetic factors, including LPA kringle IV-2 domain size, single-nucleotide polymorphisms, and interleukin-1 genotypes. Apolipoprotein(a) is encoded by the LPA gene and contains 10 subtypes with a variable number of copies of kringle -2, resulting in >40 different apolipoprotein(a) isoform sizes. Genetic loci beyond LPA, such as APOE and APOH, have been shown to impact lipoprotein(a) levels. Lipoprotein(a) concentrations are generally 5% to 10% higher in women than men, and there is up to a 3-fold difference in median lipoprotein(a) concentrations between racial and ethnic populations. Nongenetic factors, including menopause, diet, and renal function, may also impact lipoprotein(a) concentration. Lipoprotein(a) levels are also influenced by inflammation since the LPA promoter contains an interleukin-6 response element; interleukin-6 released during the inflammatory response results in transient increases in plasma lipoprotein(a) levels. Screening can identify elevated lipoprotein(a) levels and facilitate intensive risk factor management. Several investigational, RNA-targeted agents have shown promising lipoprotein(a)-lowering effects in clinical studies, and large-scale lipoprotein(a) testing will be fundamental to identifying eligible patients should these agents become available. Lipoprotein(a) testing requires routine, nonfasting blood draws, making it convenient for patients. Herein, we discuss the genetic determinants of lipoprotein(a) levels, explore the pathophysiological mechanisms underlying the association between lipoprotein(a) and cardiovascular disease, and provide practical guidance for lipoprotein(a) testing.

Elevated Lp(a): Guidance for Identifying and Managing Patients.

Lipoprotein(a) (Lp(a)) is a unique low-density lipoprotein-like lipoprotein that is considered an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. The Lp(a) molecule also contains apolipoprotein A and apolipoprotein B, which collectively promote atherosclerosis, thrombosis, and inflammation. Lp(a) is highly genetic and minimally responsive to nonpharmacological measures. Lp(a) serum levels ≥125 nmol/L are associated with increased ASCVD risk, but this threshold has not been accepted universally. Elevated Lp(a) is the most common genetic dyslipidemia affecting approximately 20% of the general population. Certain currently available lipid-lowering drugs, including the proprotein convertase subtilisin/kexin type 9 therapies, produce moderate reductions in Lp(a); however, none are indicated for the treatment of elevated Lp(a). There are currently four investigational RNA-based therapeutic agents that reduce Lp(a) by 70% to 100%. Two of these agents are being evaluated for ASCVD risk reduction in adequately powered outcomes trials, with results expected in 2 to 3 years. Until such therapies become available and demonstrate favorable clinical outcomes, strategies for elevated Lp(a) primarily involve early and intensive ASCVD risk factor management.

Carotid Artery Stenting

Currently, stricter indications for carotid artery stenosis are required owing to improvements in multifaceted medical treatment, including the intensive management of risk factors for atherosclerosis and lifestyle changes. High-risk factors for carotid artery stenting, such as vulnerable plaques, severe calcification, pseudo-occlusion, and difficult access, should be evaluated before endovascular intervention. Therefore, we need to understand the characteristics of each device to achieve maximum risk reduction for carotid artery stenting.

Lipoprotein(a): An important piece of the ASCVD risk factor puzzle across diverse populations

Elevated lipoprotein(a) (Lp[a]) is an independent, genetic risk factor for atherosclerotic cardiovascular disease (ASCVD) that impacts ~1.4 billion people globally. Generally, Lp(a) levels remain stable over time; thus, most individuals need only undergo Lp(a) testing through a non-fasting blood draw once in their lifetime, unless elevated Lp(a) is identified. Despite the convenience of the test for clinicians and patients, routine Lp(a) testing has not been widely adopted. This review provides a guide to the benefits of Lp(a) testing and solutions for overcoming common barriers in practice, including access to testing and lack of awareness. Lp(a) testing provides the opportunity to reclassify ASCVD risk and drive intensive cardiovascular risk factor management in individuals with elevated Lp(a), and to identify patients potentially less likely to respond to statins. Moreover, cascade screening can help to identify elevated Lp(a) in relatives of individuals with a personal or family history of premature ASCVD. Overall, given the profound impact of elevated Lp(a) on cardiovascular risk, Lp(a) testing should be an essential component of risk assessment by primary and specialty care providers.

Abstract 17474: Factors Affecting Cognitive Status in Patients With Intracranial Atherosclerosis After Surgical Revascularization: A Post Hoc Analysis of ERSIAS Phase-2 Performance Criterion (PC) Trial

Introduction: Cognitive decline affects a large proportion of patients with ischemic stroke. Intracranial atherosclerotic disease (ICAD) is a common stroke etiology associated with a high and prolonged risk of recurrence. In the ERSIAS phase-II trial, patients with symptomatic ICAD received revascularization with encephaloduroarteriosynangiosis (EDAS) plus intensive medical management (IMM) of stroke risk factors. We present a subgroup analysis of features affecting cognitive outcomes. Hypothesis: To evaluate the factors contributing to cognitive decline in patients who underwent revascularization for symptomatic ICAD. Methods: ERSIAS patients without aphasia that completed at least one year of follow-up were included. Cognitive status was evaluated using MoCA at baseline and each follow-up and classified as improved/preserved vs. worsened. Classification and Regression Tree Analysis (CART) was used to identify factors associated with changes in cognitive function. Factors considered were age, sex, stenosis vs. occlusion, baseline-mRS, good collateralization and compliance with diabetes (DM) hypertension (HTN), and hyperlipidemia (HLD) treatments. Results: In ERSIAS, the mean MoCA at baseline was 22.4 (SD 4.9), and 23.9 (SD 4.9) at one-year follow-up in the complete population. Thirty-nine patients were included in this analysis. Median age was 46 (IQR 37.0-56.0), and 27 (69.2%) were female. MoCA improved or remained stable in 33 (84.6%) patients and declined in 6 (15.4%). CART analysis revealed that the most relevant factors for improved MoCA were compliance with DM treatment (94.5%(yes) vs.74.2%(no) p=0.02) HLD treatment (83.3% (yes) 60.5%(no) p=0.2) and stenosis 99.1% vs. occlusion 80.9%, p=0.6 Other factors where not found to be contributory. Conclusions: Compliance with DM treatment is a significant predictor of cognitive preservation in symptomatic ICAD patients. Our findings emphasize the importance of IMM of stroke risk factors in patients with intracranial atherosclerosis, even after surgical revascularization.

Lower extremity arterial disease

Abstract: Lower Limbs Arterial Disease (LEAD) affects over 40 million people in Europe and appears to be 2-4 times more prevalent in people with type 2 diabetes (PWT2D) than in the general population. LEAD patients need intensive prevention and management of risk factors. Cigarette smoking is one of the most important risk factors for peripheral arterial disease as well as hyperlipoproteinemia and hypertension. Diabetic metabolic disorders are the most important risk factors for LEAD progression. The antiplatelet drugs represent one of the basic options for the management of patients with various atherosclerotic diseases. Aspirin is the oldest and most often prescribed antiplatelet drug. Lifestyle management remains the cornerstones of LEAD patients management.

Consensus document on Lipoprotein(a) from the Italian Society for the Study of Atherosclerosis (SISA)

AimsIn view of the consolidating evidence on the causal role of Lp(a) in cardiovascular disease, the Italian Society for the Study of Atherosclerosis (SISA) has assembled a consensus on Lp(a) genetics and epidemiology, together with recommendations for its measurement and current and emerging therapeutic approaches to reduce its plasma levels. Data on the Italian population are also provided. Data synthesisLp(a) is constituted by one apo(a) molecule and a lipoprotein closely resembling to a low-density lipoprotein (LDL). Its similarity with an LDL, together with its ability to carry oxidized phospholipids are considered the two main features making Lp(a) harmful for cardiovascular health. Plasma Lp(a) concentrations vary over about 1000 folds in humans and are genetically determined, thus they are quite stable in any individual. Mendelian Randomization studies have suggested a causal role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis and observational studies indicate a linear direct correlation between cardiovascular disease and Lp(a) plasma levels. Lp(a) measurement is strongly recommended once in a patient's lifetime, particularly in FH subjects, but also as part of the initial lipid screening to assess cardiovascular risk. The apo(a) size polymorphism represents a challenge for Lp(a) measurement in plasma, but new strategies are overcoming these difficulties. A reduction of Lp(a) levels can be currently attained only by plasma apheresis and, moderately, with PCSK9 inhibitor treatment. ConclusionsAwaiting the approval of selective Lp(a)-lowering drugs, an intensive management of the other risk factors for individuals with elevated Lp(a) levels is strongly recommended.

Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial

BackgroundThe superiority of balloon angioplasty plus aggressive medical management (AMM) to AMM alone for symptomatic intracranial artery stenosis (sICAS) on efficacy and safety profiles still lacks evidence from randomised controlled...

Hyperlipidemia and Cardiovascular Disease in People with Type 1 Diabetes: Review of Current Guidelines and Evidence

In this review, we discuss the prevalence of cardiovascular disease in people with type 1 diabetes. We outline key risk factors associated with increased cardiovascular event rates and discuss the prevalence and mechanisms underlying hyperlipidemia in people with type 1 diabetes. Finally, we summarize the evidence to support early and more aggressive lipid-lowering therapy in people with type 1 diabetes and review current guideline recommendations. Comprehensive treatment of hyperglycemia, hypertension, and hyperlipidemia reduces adverse cardiovascular outcomes in people with type 2 diabetes. In contrast, evidence to support a comparable benefit of intensive cardiovascular risk factor management in people with type 1 diabetes is lacking from prospective, randomized trials and has only been shown in registries. Therefore, current treatment guidelines extrapolate prospective clinical trial evidence obtained in people with type 2 diabetes to provide similar treatment recommendations for people with type 1 and type 2 diabetes. Evidence supports the more aggressive treatment of cardiovascular risk factors in people with type 1 diabetes, who would likely benefit from early risk stratification and comprehensive risk factor management, including aggressive lipid-lowering therapy.

Abstract 14524: Low Testosterone Levels and Cardiovascular Disease: Insights From the Houston Methodist CVD Registry

Introduction: Low testosterone (LowT) has been suggested to be associated with increased ASCVD risk and mortality, but results are conflicting across studies. We evaluated the independent relationship between low testosterone levels in adult males and ASCVD using data from an EHR-based database. Methods Cross-sectional study using the Houston Methodist CVD Learning Health System Registry, which includes data from 1.1 million patients aged ≥18 years (June 2016-April 2022). Analyses were restricted to men, and those on testosterone replacement therapy were excluded. We evaluated the associations between total testosterone levels (categorized as quartiles [Q], lowest Q as exposure of interest and highest Q as reference) and ASCVD (CAD, PAD, stroke), using logistic regression. Conditions and risk factors were identified using ICD 10-CM codes. Results: We evaluated 30,150 men ≥18 years (mean age 55.3 years, 12% NHB, 15% Hispanics) with testosterone level data. Men in testosterone Q1 (lowest levels: ≤285 ng/dl) had higher prevalence of almost all risk factors and composite ASCVD compared to Q4 (highest levels: ≥515 ng/dl) (Panel A). In unadjusted analyses, men in testosterone Q1 vs Q4 had higher odds of ASCVD (OR 1.54, 95% CI 1.41-1.68). In multivariable adjusted logistic regression, the increased odds persisted adjusting for age, sex, and race OR 1.33 (CI 1.21 - 1.46), while it was fully attenuated (OR 1.04 CI 0.94 - 1.14) after adjusting for risk factors (DM, HTN, dyslipidemia, obesity) (Panel B). The attenuation in association with prevalent ASCVD was highest adjusting for DM (67%) and HTN (58%) (Panel C). Similar results were noted when cutoff of <200 ng/dl was used for LowT. Conclusions: ASCVD and CV risk factors are widely prevalent among men with LowT. The association between LowT and ASCVD might be related to CV risk factors, mainly hypertension and DM. Early identification and intensive CV risk factor management among men with LowT levels may help reduce their risk of ASCVD.

Lp(a) and its role in cardiovascular diseases

Lipoprotein(a) - Lp(a) - is an hepatically synthesized lipoprotein, structurally similar to low-density-lipoprotein, and an important marker for cardiovascular risk. Lp(a) plasma concentrations are genetically determined and can hardly be modified by diet, exercise or oral drugs. Lp(a) concentration should be tested at least once per life. The current treatment for high Lp(a) is early intensive risk factor management with optimal lowering of LDL-cholesterol. Potent new RNA-targeting therapies are currently assessed in clinical trials and may be available in a couple of years.

Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement.

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis.

Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics

Diabetic kidney disease (DKD) is a prevalent renal complication of diabetes mellitus that ultimately develops into end-stage kidney disease (ESKD) when not managed appropriately. Substantial risk of ESKD remains even with intensive management of hyperglycemia and risk factors of DKD and timely use of renin-angiotensin-aldosterone inhibitors. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce hyperglycemia primarily by inhibiting glucose and sodium reabsorption in the renal proximal tubule. Currently, their effects expand to prevent or delay cardiovascular and renal adverse events, even in those without diabetes. In dedicated renal outcome trials, SGLT2 inhibitors significantly reduced the risk of composite renal adverse events, including the development of ESKD or renal replacement therapy, which led to the positioning of SGLT2 inhibitors as the mainstay of chronic kidney disease management. Multiple mechanisms of action of SGLT2 inhibitors, including hemodynamic, metabolic, and anti-inflammatory effects, have been proposed. Restoration of tubuloglomerular feedback is a plausible explanation for the alteration in renal hemodynamics induced by SGLT2 inhibition and for the associated renal benefit. This review discusses the clinical rationale and mechanism related to the protection SGLT2 inhibitors exert on the kidney, focusing on renal hemodynamic effects.

Long-Term Prognosis of Acute Myocardial Infarction Associated With Metabolic Health and Obesity Status

ObjectiveEmerging evidence supports the favorable cardiovascular health in nonobese subjects with healthy metabolism. However, little is known regarding the prognosis across the range of metabolic phenotypes once cardiovascular disease is established. We examined the prognosis of patients with acute myocardial infarction (AMI) stratified according to metabolic health and obesity status. MethodsThis is a retrospective study on consecutive patients with AMI admitted to a tertiary hospital between 2014 and 2021. Patients were allocated into the following 4 groups based on metabolic and obesity profile: (1) metabolically healthy obese (MHO), (2) metabolically healthy nonobese (MHNO), (3) metabolically unhealthy obese (MUO), and (4) metabolically unhealthy nonobese (MUNO). Metabolic health was defined in accordance to the Biobank Standardisation and Harmonisation for Research Excellence in the European Union Healthy Obese Project. The primary outcome was all-cause mortality. The Cox regression analysis examined the independent association between mortality and metabolic phenotypes, adjusting for age, sex, AMI type, chronic kidney disease, smoking status, and left ventricular ejection fraction. ResultsOf 9958 patients, the majority (68.5%) were MUNO, followed by MUO (25.1%), MHNO (5.6%), and MHO (0.8%). MHO had the lowest mortality (7.4%), followed by MHNO (9.7%), MUO (19.2%), and MUNO (22.6%) (P < .001). Compared with MHNO, MUO (hazard ratio [HR], 1.737; 95% confidence interval [CI], 1.282-2.355; P < .001) and MUNO (HR, 1.482; 95% CI, 1.108-1.981; P = .008) had a significantly higher mortality risk but not MHO (HR, 1.390; 95% CI, 0.594-3.251; P = .447), after adjusting for confounders. The Kaplan-Meier curves showed favorable survival in the metabolically healthy and obesity groups, with the highest overall survival in the MHO, followed by MHNO, MUO, and MUNO (P < .001). ConclusionMetabolically healthy and obese patients with AMI have favorable prognosis compared with metabolically unhealthy and nonobese patients. It is equally important to prioritize intensive metabolic risk factor management to weight reduction in the early phase after AMI.

Encephaloduroarteriosynangiosis Operative Technique and Intraoperative Anesthesia Management: Treatment From Both Sides of the Curtain.

Encephaloduroarteriosynangiosis (EDAS) is a form of indirect revascularization for cerebral arterial steno-occlusive disorders. EDAS has gained growing interest as a technique applicable to pediatric and adult populations for several types of ischemic cerebral steno-occlusive conditions. To present a team-oriented, multidisciplinary update of the EDAS technique for application in challenging adult cases of cerebrovascular stenosis/occlusion, successfully implemented in more than 200 cases. We describe and demonstrate step-by-step a multidisciplinary-modified EDAS technique, adapted to maintain uninterrupted intensive medical management of patients' stroke risk factors and anesthesia protocols to maintain strict hemodynamic control. A total of 216 EDAS surgeries were performed in 164 adult patients, including 65 surgeries for patients with intracranial atherosclerotic disease and 151 operations in 99 patients with moyamoya disease. Five patients with intracranial atherosclerotic disease had recurrent strokes (3%), and there was one perioperative death. The mean clinical follow-up was 32.9 mo with a standard deviation of 31.1. There was one deviation from the surgical protocol. There were deviations from the anesthesia protocol in 3 patients (0.01%), which were promptly corrected and did not have any clinical impact on the patients' condition. The EDAS protocol described here implements a team-oriented, multidisciplinary adaptation of the EDAS technique. This adaptation resides mainly in 3 points: (1) uninterrupted administration of intensive medical management, (2) strict hemodynamic control during anesthesia, and (3) meticulous standardized surgical technique.

Mortality and cardiovascular outcomes in patients with diabetes and probable familial hypercholesterolemia

Background and Aims: Heterozygous familial hypercholesterolemia (FH) is a hereditary dyslipidaemia causing premature atherosclerotic cardiovascular disease (ASCVD) and death due to high LDL cholesterol levels. Similarly, patients with diabetes have increased risk of ASCVD and mortality despite intensive risk factor management. There is limited data on prognosis in patients with both diabetes and FH. Aim is to assess prognosis in individuals with both FH and diabetes.

Intensive risk factor management and cardiovascular autonomic neuropathy in type2 diabetes in the Action to Control Cardiovascular Risk in Diabetes trial: A post-hoc analysis.

In people with type 1 or 2 diabetes, cardiovascular autonomic neuropathy (CAN) is associated with the development of atherosclerotic cardiovascular disease (CVD) and with a high risk of lethal arrhythmias and sudden death. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which included people with type 2 diabetes, participants with CAN at baseline were 1.55 to 2.14 times more likely to die than participants without CAN, and the presence of orthostatic hypotension (OH) at baseline was also associated with an increased risk of total death (hazard ratio, 1.61) and death or hospitalization due to heart failure (hazard ratio, 1.85).

Cardiometabolic profile of type 2 diabetic subjects in Libreville

Type 2 diabetes is the chronic metabolic disease associated with cardiovascular, renal and neurological complications, responsible for morbidity and mortality. In addition, the incidence of cardiovascular disease was 10.3 out of 1000 type 2 diabetics per year in low-income countries like Gabon. Thus, this work was setup to determine the cardiometabolic profile of type 2 diabetic subjects in Libreville. This was a cross-sectional analytical study, which took place at the Endocrinology Department of the University Hospital Center of Libreville (CHUL) and at the Biochemistry Laboratory of Health Sciences University (USS). 210 subjects were enrolled, including 95 diabetics and 115 controls. Their anthropometric values were recorded and biochemical parameters obtained by spectrophotometric methods. Metabolic syndrome was defined according to NCEP ATP III criteria, and 10-years cardiovascular risk was assessed using Framingham and American Heart Association (AHA) / ACC risk scores.The metabolic syndrome was found among 75.8% of diabetics against 24.2% among controls (p = 0.000). In all, 42.1% of diabetics had a high cardiovascular risk by the Framingham equation versus 6.1% for the controls and 41.1% with the AHA / ACC score versus 4.3% for the controls. Diabetic women were more affected than men (54.6% against 13.8% p = 0.000).Type 2 diabetics should undergo intensive management of cardiovascular risk factors in order to reduce the level of cardiovascular risk. Thus their life shall be improved by reducing morbidity and mortality.

Rationale, Design, and Implementation of Intensive Risk Factor Treatment in the CREST2 Trial

A subanalysis of patients entered in the CREST2 trial (carotid revascularization and medical management for asymptomatic carotid stenosis) from 2014 to March 23, 2020 was performed. Interim risk factor data were gathered for 1618 patients at baseline and follow-up through 24 months analyzing intensive medical management alone compared with intensive medical management plus carotid endarterectomy or transfemoral carotid artery stenting for preventing stroke or death. The mean baseline low-density lipoprotein level was 80 mg/dL, which had significantly improved to 67 mg/dL after intensive medical treatment. The mean baseline systolic blood pressure of 140 mm Hg had significantly improved to 130 mm Hg. A rigorous approach to intensive stroke risk factor management in CREST2 resulted in significant improvements in risk factor control.