Prof. Dr. John J.P. Kastelein of the Department of Vascular Medicine, Amsterdam UMC, and the University of Amsterdam speaks about New and Emerging Therapies for Reduction of LDL-Cholesterol and Apolipoprotein B: JACC Focus Seminar 1/4.
Link to Article:
https://www.jacc.org/doi/10.1016/j.jacc.2020.11.079?utm_medium=social&utm_source=twitter_post&utm_campaign=twitter_post
Summary -
Novel, emerging low-density lipoprotein cholesterol (LDL-C)–lowering therapies are under development for the prevention of cardiovascular disease, adding to the base of statins, ezetimibe, and proprotein convertase subtilisin–kexin type 9 inhibitors (PCSK9i). Inclisiran, a PCSK9-inhibiting small interfering RNA molecule that only needs to be dosed twice a year, has the ability to help address existing obstacles to lipid-lowering therapy persistence and adherence. Patients with statin intolerance can benefit from bempedoic acid, which lowers LDL-C upstream from statins. In patients with homozygous familial hypercholesterolemia, angiopoetin-like 3 protein (ANGPTL3) inhibitors have been shown to provide potent LDL-C lowering without the significant side effects seen with lomitapide and mipomersen, and may minimize the need for apheresis. Finally, with the production of obicetrapib, CETP inhibitors may still be effective. From primary prevention and secondary prevention to null-null homozygous hereditary hypercholesterolemia patients, these novel agents provide clinicians the resources they need to effectively lower LDL-C across the entire spectrum of LDL-C–induced elevations of cardiovascular danger.
Aspects to Consider
• Despite existing methods, atherosclerotic cardiovascular disease continues to be a major problem.
• Low-density lipoprotein cholesterol (LDL-C) is a significant cause of atherosclerotic cardiovascular disease.
• The most commonly used pharmacological agents for reducing LDL-C are statins, ezetimibe, and PCSK9 inhibitor monoclonal antibodies.
• Inclisiran, bempedoic acid, ANGPTL3, and CETP inhibitors, all of which are still in production, have the potential to reduce residual LDL-C risk.
Cardiovascular Disease
Description
Cardiovascular Disease
Imke Janssen, PhD, Associate Professor, Department of Preventive Medicine, Rush Medical College. In this video, she speaks about Psychosocial Well‐Being and Progression of Coronary Artery Calcification in Midlife Women.
Observation -
Back story
Preventing cardiovascular disease (CVD) is a public health concern. Physical activity, a healthy diet, and stopping smoking are all important preventative factors, although aspects of psychosocial well-being have generally been researched separately, with inconsistent results. The purpose of this study was to examine if a combination of psychological well-being indices was associated with slower coronary artery calcium development (CAC).
Methodology and Findings
The SWAN (Research of Women's Health Across the Nation) auxiliary Heart Study included 312 women (mean age 50.8) who were all free of clinical CVD at the start of the study. Six validated psychosocial questionnaires measuring optimism, vitality, life engagement, life satisfaction, multitasking, and positive affect were integrated to create a composite psychosocial well-being score. Subclinical CAC development was characterized as an increase of 10 Agatston units over 2.3 years using electron beam tomography. The effect of happiness on CAC progression was studied using relative risk (RR) regression models that were controlled for sociodemographic characteristics, depression, healthy lifestyle habits, and traditional CVD risk factors. At the outset, 42.9 percent of participants had a CAC score of >0, and 17.6 percent progressed. Well-being was associated with lower progression after controlling for potential confounders, depression, and health practices (RR, 0.909; 95 percent CI, 0.8430.979; P=0.012). Further adjustment for conventional CVD risk factors reduced the total group's risk (RR, 0.943; 95 percent CI, 0.8711.020; P=0.142), but the 134 women with baseline CAC>0 remained significant (RR, 0.921; 95 percent CI, 0.8520.995; P=0.037).
Implications
Incorporating the mental side of the mindheartbody continuum may result in the best early CVD prevention in women.
Imke Janssen, PhD, Associate Professor, Department of Preventive Medicine, Rush Medical College. In this video, she speaks about Psychosocial Well‐Being and Progression of Coronary Artery Calcification in Midlife Women.
Observation -
Back story
Preventing cardiovascular disease (CVD) is a public health concern. Physical activity, a healthy diet, and stopping smoking are all important preventative factors, although aspects of psychosocial well-being have generally been researched separately, with inconsistent results. The purpose of this study was to examine if a combination of psychological well-being indices was associated with slower coronary artery calcium development (CAC).
Methodology and Findings
The SWAN (Research of Women's Health Across the Nation) auxiliary Heart Study included 312 women (mean age 50.8) who were all free of clinical CVD at the start of the study. Six validated psychosocial questionnaires measuring optimism, vitality, life engagement, life satisfaction, multitasking, and positive affect were integrated to create a composite psychosocial well-being score. Subclinical CAC development was characterized as an increase of 10 Agatston units over 2.3 years using electron beam tomography. The effect of happiness on CAC progression was studied using relative risk (RR) regression models that were controlled for sociodemographic characteristics, depression, healthy lifestyle habits, and traditional CVD risk factors. At the outset, 42.9 percent of participants had a CAC score of >0, and 17.6 percent progressed. Well-being was associated with lower progression after controlling for potential confounders, depression, and health practices (RR, 0.909; 95 percent CI, 0.8430.979; P=0.012). Further adjustment for conventional CVD risk factors reduced the total group's risk (RR, 0.943; 95 percent CI, 0.8711.020; P=0.142), but the 134 women with baseline CAC>0 remained significant (RR, 0.921; 95 percent CI, 0.8520.995; P=0.037).
Implications
Incorporating the mental side of the mindheartbody continuum may result in the best early CVD prevention in women.
Raymond R. Townsend, MD, Researcher Physician at University of Pennsylvania. In this video, he speaks about the SPYRAL HTN-ON MED Study.
In summation,
Origins:
Intraoperative hypothermia of moderate severity causes myocardial damage, surgical site infections, and blood loss. It is unknown whether forceful warming to a true normothermic temperature approaching 37°C improves outcomes. We wanted to see if intensive intraoperative warming minimizes severe perioperative problems.
Methodologies:
During non-cardiac surgery, patients were randomly assigned (1:1) to either aggressive warming to a target core temperature of 37°C (aggressively warmed group) or routine thermal management to a target of 35°C (routine thermal management group) at 12 sites in China and the Cleveland Clinic in the United States. Randomization was stratified by location, with randomly sized blocks generated by a computer. Eligible patients (aged 45 years) had at least one cardiovascular risk factor, were scheduled for inpatient non-cardiac surgery lasting 2–6 hours under general anaesthesia, and had at least half of the anterior skin surface available for warming. Patients on dialysis and those with a BMI more than 30 kg/m2 were excluded. In the modified intention-to-treat population, the primary outcome was a composite of myocardial damage (troponin increase, probably of ischemic origin), non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery. NCT03111875, this study is registered with ClinicalTrials.gov.
Conclusions:
5056 participants were enrolled between March 27, 2017 and March 16, 2021, with 5013 included in the intention-to-treat population (2507 in the aggressively warmed group and 2506 in the routine thermal management group). Patients allocated to intense warming had a mean final intraoperative core temperature of 371°C (SD 03), whereas patients assigned to regular thermal care had a mean final intraoperative core temperature of 356°C (SD 03). At least one of the primary outcome components (myocardial damage following non-cardiac surgery, cardiac arrest, or mortality) occurred in 246 (99% of 2497) of the forcefully warmed patients and in 239 (96% of 2490) of the normal thermal care patients. The calculated common impact relative risk of active versus routine thermal management was 104 (95 percent CI 087–124; p=069). There were 39 adverse events (17 of which were significant) in patients assigned to intense warming and 54 in those assigned to normal thermal care (30 of which were serious). One major adverse event in a patient who had been intensively warmed was thought to be connected to thermal management.
Observation:
The 30-day composite of main cardiovascular events did not differ substantially between participants randomly assigned to 355°C or 37°C. There was no evidence that any significant consequence differed throughout a 15°C range from extremely mild hypothermia to full normothermia. In surgical patients, maintaining a core temperature of at least 355°C appears to be sufficient.
Raymond R. Townsend, MD, Researcher Physician at University of Pennsylvania. In this video, he speaks about the SPYRAL HTN-ON MED Study.
In summation,
Origins:
Intraoperative hypothermia of moderate severity causes myocardial damage, surgical site infections, and blood loss. It is unknown whether forceful warming to a true normothermic temperature approaching 37°C improves outcomes. We wanted to see if intensive intraoperative warming minimizes severe perioperative problems.
Methodologies:
During non-cardiac surgery, patients were randomly assigned (1:1) to either aggressive warming to a target core temperature of 37°C (aggressively warmed group) or routine thermal management to a target of 35°C (routine thermal management group) at 12 sites in China and the Cleveland Clinic in the United States. Randomization was stratified by location, with randomly sized blocks generated by a computer. Eligible patients (aged 45 years) had at least one cardiovascular risk factor, were scheduled for inpatient non-cardiac surgery lasting 2–6 hours under general anaesthesia, and had at least half of the anterior skin surface available for warming. Patients on dialysis and those with a BMI more than 30 kg/m2 were excluded. In the modified intention-to-treat population, the primary outcome was a composite of myocardial damage (troponin increase, probably of ischemic origin), non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery. NCT03111875, this study is registered with ClinicalTrials.gov.
Conclusions:
5056 participants were enrolled between March 27, 2017 and March 16, 2021, with 5013 included in the intention-to-treat population (2507 in the aggressively warmed group and 2506 in the routine thermal management group). Patients allocated to intense warming had a mean final intraoperative core temperature of 371°C (SD 03), whereas patients assigned to regular thermal care had a mean final intraoperative core temperature of 356°C (SD 03). At least one of the primary outcome components (myocardial damage following non-cardiac surgery, cardiac arrest, or mortality) occurred in 246 (99% of 2497) of the forcefully warmed patients and in 239 (96% of 2490) of the normal thermal care patients. The calculated common impact relative risk of active versus routine thermal management was 104 (95 percent CI 087–124; p=069). There were 39 adverse events (17 of which were significant) in patients assigned to intense warming and 54 in those assigned to normal thermal care (30 of which were serious). One major adverse event in a patient who had been intensively warmed was thought to be connected to thermal management.
Observation:
The 30-day composite of main cardiovascular events did not differ substantially between participants randomly assigned to 355°C or 37°C. There was no evidence that any significant consequence differed throughout a 15°C range from extremely mild hypothermia to full normothermia. In surgical patients, maintaining a core temperature of at least 355°C appears to be sufficient.
Amgad Mentias, MD, MS, FACC, FEDSC, Clinical Cardiologist at the Cleveland Clinic. In this video, he speaks about the abstract Long-Term Cardiovascular Outcomes After Bariatric Surgery in the Medicare Population.
Observation -
Origins:
The long-term impact of bariatric surgery on cardiovascular outcomes in the senior population has not been well investigated.
Purpose:
The purpose of this study was to look at the relationship between bariatric surgery and long-term cardiovascular outcomes in the Medicare group.
Methodologies:
Medicare beneficiaries who underwent bariatric surgery between 2013 and 2019 were matched to a control group of obese patients using a 1:1 exact match based on age, gender, BMI, and propensity score matching on 87 clinical characteristics. All-cause mortality, new-onset heart failure (HF), myocardial infarction (MI), and ischemic stroke were among the study's results. As a sensitivity analysis, an instrumental variable analysis was undertaken.
Outcomes:
There were 189,770 patients in the study cohort (94,885 matched patients in each group). According to the study design, the two groups were similar in age (mean: 62.33 10.62 years), gender (70 percent female), and degree of obesity (mean body mass index: 44.7 7.3 kg/m2), as well as on all clinical characteristics. Bariatric surgery was linked with a decreased risk of death (9.2 vs 14.7 per 1,000 person-years; HR: 0.63; 95 percent CI: 0.60-0.66), new-onset HF (HR: 0.46; 95 percent CI: 0.44-0.49), MI (HR: 0.63; 95 percent CI: 0.59-0.68), and stroke (HR: 0.71; 95 percent CI: 0.65-0.79) (P 0.001). The benefit of bariatric surgery was seen in patients aged 65 and up. Using instrumental variable analysis, bariatric surgery was linked to a decreased risk of death, heart failure, and MI.
Observations:
Bariatric surgery is related with a decreased risk of death, new-onset HF, and MI among Medicare seniors who are obese.
Amgad Mentias, MD, MS, FACC, FEDSC, Clinical Cardiologist at the Cleveland Clinic. In this video, he speaks about the abstract Long-Term Cardiovascular Outcomes After Bariatric Surgery in the Medicare Population.
Observation -
Origins:
The long-term impact of bariatric surgery on cardiovascular outcomes in the senior population has not been well investigated.
Purpose:
The purpose of this study was to look at the relationship between bariatric surgery and long-term cardiovascular outcomes in the Medicare group.
Methodologies:
Medicare beneficiaries who underwent bariatric surgery between 2013 and 2019 were matched to a control group of obese patients using a 1:1 exact match based on age, gender, BMI, and propensity score matching on 87 clinical characteristics. All-cause mortality, new-onset heart failure (HF), myocardial infarction (MI), and ischemic stroke were among the study's results. As a sensitivity analysis, an instrumental variable analysis was undertaken.
Outcomes:
There were 189,770 patients in the study cohort (94,885 matched patients in each group). According to the study design, the two groups were similar in age (mean: 62.33 10.62 years), gender (70 percent female), and degree of obesity (mean body mass index: 44.7 7.3 kg/m2), as well as on all clinical characteristics. Bariatric surgery was linked with a decreased risk of death (9.2 vs 14.7 per 1,000 person-years; HR: 0.63; 95 percent CI: 0.60-0.66), new-onset HF (HR: 0.46; 95 percent CI: 0.44-0.49), MI (HR: 0.63; 95 percent CI: 0.59-0.68), and stroke (HR: 0.71; 95 percent CI: 0.65-0.79) (P 0.001). The benefit of bariatric surgery was seen in patients aged 65 and up. Using instrumental variable analysis, bariatric surgery was linked to a decreased risk of death, heart failure, and MI.
Observations:
Bariatric surgery is related with a decreased risk of death, new-onset HF, and MI among Medicare seniors who are obese.
Metabolic epidemiology of CVD risk in young adulthood: A "blind spot" in prevention
The Cardiovascular Diseases of the Poorest Billion: Toward a Science of Integration
Robert H. Eckel, MD, Division of Endocrinology, Metabolism, and Diabetes, Division of Cardiology, University of Colorado Anschutz Medical Campus speaks about Review Article - Cardiovascular effects of omega-3 fatty acids: Hope or hype?
Link to Article:
https://www.atherosclerosis-journal.com/article/S0021-9150(21)00086-1/abstract#%20
Introduction:
After a clinical trial (REDUCE-IT) revealed excellent outcomes with icosapent ethyl (IPE) in patients undergoing maximally tolerated statin treatment, omega-3 fatty acids have emerged as a novel alternative for reducing the residual risk of cardiovascular disease (CVD) in the statin era. Another experiment (STRENGTH) that employed a high dose of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) combination failed. These findings pose clinically significant issues when taken together. Are the effects of omega-3 fatty acids neutral, helpful, or perhaps detrimental in individuals on statin therapy? Different kinds of omega-3 fatty acids (just EPA or EPA + DHA), dosages (greater vs. lower dose) of omega-3 fatty acids, or comparators (corn oil or mineral oil), as well as the underlying severity of the CVD risk or usage of statins, might explain the present conflicting results.
In addition to these topics, we will examine the biological and clinical consequences of various kinds of omega-3 fatty acids, as well as how to assess the findings of historical and current clinical research and provide practical recommendations for patient treatment.