Classic endocrine disorders: implications for cardiovascular disease

Chronic underproduction or autonomous oversecretion of hormone by endocrine glands has implications for the development and progression of cardiovascular disease. Hormonal effects on the vasculature may be direct, for example, tachycardia and atrial arrhythmias in hyperthyroidism, or mediated indirectly via adverse profiles of one or more major cardiovascular risk factors, for example, arterial hypertension in Conn's syndrome. The timescale of vascular effects may be relatively rapid, for example, resting tachycardia or atrial fibrillation precipitated by hyperthyroidism, or long-term, for example, atherosclerosis associated with acromegaly or hypopituitarism of long duration. The COVID-19 pandemic has highlighted clinically important interactions between the endocrine, metabolic, and cardiovascular systems. Endocrinologists and cardiologists will often need to collaborate closely in the management of patients with endocrine-associated vascular disease. © 2023 Elsevier Inc. All rights reserved.

Barriers and shortcomings in access to cardiovascular management and prevention for familial hypercholesterolemia during the COVID-19 pandemic.

Familial hypercholesterolemia (FH) is a hereditary condition caused by mutations in the lipid pathway. The goal in managing FH is to reduce circulating low-density lipoprotein cholesterol and, therefore, reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Because FH patients were considered high risk groups due to an increased susceptible for contracting COVID-19 infection, we hypothesized whether the effects of the pandemic hindered access to cardiovascular care. In this review, we conducted a literature search in databases Pubmed/Medline and ScienceDirect. We included a comprehensive analysis of findings from articles in English related and summarized the effects of the pandemic on cardiovascular care through direct and indirect effects. During the COVID-19 pandemic, FH patients presented with worse outcomes and prognosis, especially those that have suffered from early ASCVD. This caused avoidance in seeking care due to fear of transmission. The pandemic severely impacted consultations with lipidologists and cardiologists, causing a decline in lipid profile evaluations. Low socioeconomic communities and ethnic minorities were hit the hardest with job displacements and lacked healthcare coverage respectively, leading to treatment nonadherence. Lock-down restrictions promoted sedentary lifestyles and intake of fatty meals, but it is unclear whether these factors attenuated cardiovascular risk in FH. To prevent early atherogenesis in FH patients, universal screening programs, telemedicine, and lifestyle interventions are important recommendations that could improve outcomes in FH patients. However, the need to research in depth on the disproportionate impact within different subgroups should be the forefront of FH research.

SARS-CoV-2 reinfection: Adding insult to dysfunctional endothelium in patients with atherosclerotic cardiovascular disease.

In this short narrative review, we aim at defining the pathophysiological role endothelial dysfunction in the observed COVID-19-associated rise in risk of cardiovascular disease. Variants of the SARS-CoV-2 virus have caused several epidemic waves of COVID-19, and the emergence and rapid spread of new variants and subvariants are likely. Based on a large cohort study, the incidence rate of SARS-CoV-2 reinfection is about 0.66 per 10 000 person-weeks. Both the first infection and reinfection with SARS-CoV-2 increase cardiac event risk, particularly in vulnerable patients with cardiovascular risk factors and the accompanying systemic endothelial dysfunction. By worsening pre-existing endothelial dysfunction, both the first infection and reinfection with ensuing COVID-19 may turn the endothelium procoagulative and prothrombotic, and ultimately lead to local thrombus formation. When occurring in an epicardial coronary artery, the risk of an acute coronary syndrome increases, and when occurring in intramyocardial microvessels, scattered myocardial injuries will ensue, both predisposing the COVID-19 patients to adverse cardiovascular outcomes. In conclusion, considering weakened protection against the cardiovascular risk-enhancing reinfections with emerging new subvariants of SARS-CoV-2, treatment of COVID-19 patients with statins during the illness and thereafter is recommended, partly because the statins tend to reduce endothelial dysfunction.

Familial Hypercholesterolemia Patients with COVID-19-Effective Cholesterol-Lowering Therapy is Urgent both during and after Infection

Heterozygous familial hypercholesterolemia (HeFH) patients are the prime example of subjects who are at high risk for both acute myocardial infarction (AMI) and ischemic stroke during, and post, SARS-CoV-2 infection. HeFH per se, if left untreated, results in premature clinical atherosclerosis often presenting in the fourth or fifth decade of life. The other concern in HeFH is endothelial dysfunction which is already evident from early childhood. In untreated HeFH patients, the severe hypercholesterolemia causes endothelial dysfunction from an early age, and as a result thereof, atherosclerotic lesions develop prematurely, particularly in the coronary arteries, and result in further endothelial dysfunction and inflammation in these critical segments of the arterial tree. As the pre-existing endothelial dysfunction in HeFH patients is most likely sensitive to further direct and indirect SARS-CoV-2 virus-dependent damage, we can infer that HeFH serves as an example of a comorbidity that predicts a poorer prognosis with COVID-19 infection. Indeed, a large US national database study showed that patients diagnosed with HeFH and SARS-CoV-2 infection had significantly increased Annualized Incidence Density Rates (AIDRs) of AMI when compared to matched HeFH controls not having been diagnosed with SARS-CoV-2 infection. Effective cholesterol lowering is essential for the prevention, or at least alleviation, of the detrimental effects of SARS-CoV-2 infection among HeFH patients. Due to the pre-existing subclinical or even clinical atherosclerotic cardiovascular disease in subjects with HeFH, cholesterol-lowering treatment needs to be continued or, better still, intensified during, and for an extended period post, SARS-CoV-2 infection.

Cardiac Biomarkers and Risk Scores in Relation with History of Atherosclerotic Cardiovascular Disease in Patients Admitted with COVID-19: The Experience of an Eastern European Center.

BACKGROUND: Data regarding the combined prognostic role of biomarkers and risk scores in relation with the history of atherosclerotic cardiovascular disease (ASCVD) in COVID-19 patients are lacking. METHODS: The aim of this observational cohort study was to evaluate the combined prognostic value of N-terminal pro B-type natriuretic peptide (NT-pro BNP), troponin and risk scores in relation with ASCVD history in hospitalized COVID-19 patients. The primary composite endpoint was Intensive Care Unit (ICU) admission and death. RESULTS: From April 2020 to June 2022, 1066 consecutive COVID-19 patients with available biomarkers upon admission were included. During a median follow-up period of 12 days, 176 patients (16.5%) died. Independent predictors of ICU admission and death in patients with ASCVD were NT-pro BNP (HR 2.63; 95% CI, 1.65-4.18) and troponin (HR 1.51; 95% CI, 1.13-2.03). In patients without ASCVD, only NT-pro BNP was predictive for the primary endpoint (HR 1.66; 95% CI, 1.10-2.53). This remained significant after adjustment for other relevant covariates (HR 3.54; 95% CI, 1.98-6.33) in patients with ASCVD and in patients without ASCVD (HR 1.82; 95% CI, 1.02-3.26). CONCLUSIONS: These data showed the combined prognostic accuracy of NT-pro BNP and troponin in relation with ASCVD history for ICU admission and death in COVID-19 patients.

Highlights of Cardiovascular Disease Studies Presented at the 2021 American Heart Association Scientific Sessions.

PURPOSE OF REVIEW: This review highlights major studies across a broad array of topics presented at the virtual 2021 American Heart Association (AHA) Scientific Sessions. RECENT FINDINGS: Assessed studies examine a remotely delivered hypertension and lipid program in 10,000 patients across a diverse healthcare network; a cluster-randomized trial of a village doctor-led intervention for hypertension control; empagliflozin in heart failure with preserved ejection fraction (EMPEROR-Preserved); efficacy and safety of empagliflozin in hospitalized heart failure patients (EMPULSE); icosapent ethyl versus placebo in outpatients with coronavirus disease 2019 (PREPARE-IT 2); clinical safety, pharmacokinetics, and low-density lipoprotein cholesterol-lowering efficacy of MK-0161, an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor; and effects of aspirin on dementia and cognitive impairment in the ASCEND trial. Research presented at the 2021 AHA Scientific Sessions emphasized the importance of interventions for cardiovascular disease prevention.

Chronic Stress, Exercise and Cardiovascular Disease: Placing the Benefits and Risks of Physical Activity into Perspective.

Chronic stress, which has been exacerbated worldwide by the lingering COVID pandemic, has been strongly linked to cardiovascular disease (CVD). In addition, autonomic dysregulation via sustained sympathetic activity has been shown to increase the risk of arrhythmias, platelet aggregation, acute coronary syndromes and heart failure. Fortunately, effective coping strategies have been shown to attenuate the magnitude of hyperarousal associated with the stress response, including moderate-to-vigorous lifestyle activity and/or structured exercise. A good-to-excellent level of cardiorespiratory fitness also appears to be highly cardioprotective. These beneficial effects have been substantiated by numerous studies that have evaluated the levels of stress reactivity and stress recovery in physically active individuals versus matched sedentary controls, as well as before and after exercise interventions. On the other hand, unaccustomed strenuous exercise in habitually sedentary persons with underlying CVD is associated with a disproportionate incidence of acute cardiac events. Moreover, extreme exercise regimens appear to increase coronary calcification and the likelihood of developing atrial fibrillation. This review summarizes these relations and more, with specific reference to placing the benefits and risks of physical activity into perspective.

Racial and geographic disparities in influenza vaccination in the U.S. among individuals with atherosclerotic cardiovascular disease: Renewed importance in the setting of COVID-19.

INTRODUCTION: The importance of receiving an annual influenza vaccine among patients with atherosclerotic cardiovascular disease (ASCVD) is well established. With the rapid community spread and the possibility of another wave of COVID-19 infections in the fall, receiving an influenza vaccine is of particular importance to mitigate the risk associated with overlapping influenza and COVID-19 infections. METHODS: We utilized cross-sectional data from the 2016 to 2019 Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative U.S. telephone-based survey of adults 18 years or older. Race/ethnicity was our exposure of interest. We assessed the relative difference in influenza vaccination by race/ethnicity for each U.S. state in the overall U.S. population and among those with ASCVD as prevalence of receipt of influenza vaccination among Blacks or Hispanics minus prevalence among Whites divided by prevalence among Whites. We used multivariable-adjusted logistic regression models to evaluate the association between socioeconomic risk factors and receipt of influenza vaccination. RESULTS: The study population consisted of 1,747,397 participants of whom 21% were older than 65 years, 51% women, 63% White, 12% Black, 17% Hispanic, and 9% with history of ASCVD. The receipt of influenza vaccine was 38% in the overall population and 51% among those with self-reported ASCVD, which translates to approximately to 97 million and 12 million US adults, respectively. The receipt of influenza vaccine among individuals with ASCVD was 54% for Whites, 45% for Blacks, and 42% for Hispanics (p<0.001). In the overall U.S. population, the median (interquartile range) relative difference for influenza vaccination between Blacks and Whites was 17% (-27%, -9%) and -22% (-29%, -9%) between Hispanics and Whites across all U.S. states. Among individuals with and without ASCVD, age older than 65 years, greater than college education, higher income, and having a primary care physician were significantly associated with higher odds of receipt of influenza vaccination, while being employed, lack of healthcare coverage, Black race, and delay in healthcare access were significantly inversely associated with having received an influenza vaccine. CONCLUSIONS: Only 50% patients with ASCVD receive influenza vaccines. The receipt of influenza vaccination among individuals with ASCVD is lower among Blacks and Hispanics compared to Whites with significant state-level variation. There are important socioeconomic determinants that are associated with receipt of the influenza vaccine.

Rationale and design of the pragmatic randomized trial of icosapent ethyl for high cardiovascular risk adults (MITIGATE).

OBJECTIVE: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). BACKGROUND: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. METHODS: MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼ 1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. CONCLUSION: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.