Beneficial effects of prehospital use of statins in a large United States cohort of hospitalized coronavirus disease 2019 patients.

AIMS: This large cohort study aimed to assess the role of chronic statin use on COVID-19 disease severity. METHODS: An observational retrospective study from electronic medical records of hospitalized patients (n = 43 950) with COVID-19 between January and September 2020 in 185 hospitals in the United States. A total of 38 875 patients met inclusion criteria; 23 066 were included in the propensity-matched sampling with replacement cohort; 11 533 were prehospital statin users. The primary outcome was all-cause death; secondary outcomes were death from COVID-19 and serious complications. Mean, standard deviation, chi-square test, Student's t-test, linear regression, and binary and multinomial logistic regressions were used for statistical analysis. RESULTS: Among 38 875 patients, 30% were chronic statin users [mean age, 70.82 (±12.25); 47.1% women] and 70% were statin nonusers [mean age, 58.44 (±18.27); 48.5% women]. Key propensity-matched outcomes among 11 533 chronic statin users showed 20% lower risk of all-cause mortality (OR 0.80, 95% CI 0.74-0.86, P < 0.001), 23% lower risk of mortality from COVID-19 (OR 0.77, 95% CI 0.71-0.84, P < 0.001), 16% lower risk of ICU admission (OR 0.84, 95% CI 0.79-0.89, P < 0.001), 24% lower risk of critical acute respiratory distress syndrome with COVID-19 (OR 0.76, 95% CI 0.70-0.83, P < 0.001), 23% lower risk of mechanical ventilation (OR 0.77, 95% CI 0.71-0.82, P < 0.001), 20% lower risk of severe sepsis with septic shock (OR 0.80, 95% CI 0.67-0.93, P = 0.004), shorter hospital length of stay [9.87 (±8.94), P < 0.001] and brief duration of mechanical ventilation [8.90 (±8.94), P < 0.001]. CONCLUSION: Chronic use of statins is associated with reduced mortality and improved clinical outcomes in patients hospitalized for COVID-19.

Trends in Guideline-Driven Revascularization in Diabetic Patients with Multivessel Coronary Heart Disease.

In diabetes patients with chronic ≥3 vessel disease, coronary artery bypass grafting (CABG) holds a class I recommendation in the American College of Cardiology and American Heart Association (ACC/AHA) 2011 guidelines, and this classification has not changed to date. Much of the literature has focused upon whether CABG or percutaneous coronary intervention (PCI) produces better outcomes; there is a paucity of data comparing the odds of receiving these procedures. A secondary analysis was conducted in a de-identified database comprised of 30,482 patients satisfying the entry criteria. Odds of occurrence (CABG, PCI) were determined as the binary dependent variable in period 1, (17 October 2009 through 31 December 2011), and period 2 (1 January 2013 through 16 March 2015), before and after the 2011 guidelines, while controlling for gender, ethnicity/race, and ischemic heart disease as covariates. The odds of performing CABG rather than PCI in period 2 were not statistically significantly different than in period 1 (p = 0.400). The logistic regression model chi-square statistic was statistically significant, with χ2 (7) = 308.850, p < 0.0001. The Wald statistic showed that ethnicity/race (African American, Caucasian, Hispanic and Other), gender, and heart disease contributed significantly to the prediction model with p < 0.05, but ethnicity 'Unknown' did not. The odds of CABG versus PCI in period 2 were 0.98 times those in period 1 95% confidence interval (CI) = (0.925, 1.032), statistically controlling for covariates. There was no significant rise in the odds of undergoing a CABG among this dataset of high-risk patients with diabetes and multivessel coronary heart disease. Modern practice has evolved regarding patient choice and additional variables that impact the final revascularization method employed. The degree to which odds of occurrence of procedures are a reliable surrogate for provider compliance with guidelines remains uncertain.

Lipoprotein(a): Current Evidence for a Physiologic Role and the Effects of Nutraceutical Strategies.

PURPOSE: Cardiovascular (CV) diseases account for most worldwide mortality, and a higher level of lipoprotein (Lp)-(a) is recognized as a prevalent contributing risk factor. However, there is no consensus regarding nutritional strategies for lowering Lp(a) concentration. Thus, the purposes of this literature review were to: (1) critically examine data concerning the effects of dietetic interventions and nutraceutical agents on Lp(a) level; and (2) review the feasibility and utility of their clinical use. METHODS: A literature search was conducted for studies published between August 2018 and March 2019. The search was performed using the Cochrane, Medline, and Web of Science databases. In order to expand the research, there were no delimitations on the type or year of the studies. A total of 1932 articles were identified using this search procedure. After duplicates were eliminated, 740 abstracts of articles written in English were screened to identify those of highest relevance. In the final tally, a total of 152 full-text articles were included in this review. FINDINGS: Several foods and decreases in saturated fat and ethanol intake, especially red wine intake, may lower Lp(a) concentration, but limits are necessary. Coffee and tea intake may decrease Lp(a) level; further investigation is crucial before they can be considered potent Lp(a)-lowering agents. Among supplementation strategies, only l-carnitine and coenzyme Q10 are promising clinical candidates to lower Lp(a) level. Since both l-carnitine and coenzyme Q10 supplementation are commonly used for CV support, they deserve further exploration regarding clinical applicability. In contrast, despite potential CV benefits, current research fails to justify use of higher intakes of vitamin C, soy isoflavones, garlic, and ω-3 for decreasing Lp(a) concentration. IMPLICATIONS: Definitive long-term clinical trials are needed to confirm the effects of dietetic interventions and nutraceutical agents on Lp(a) concentration when anticipating improved CV outcomes.

A General Pathway Model for Improving Health Disparities: Lessons from Community and Cultural Involvement in Improving Cervical Cancer Screening in Vietnamese Women.

OBJECTIVE: Chronic diseases have become dominant in the global health landscape. Despite remarkable advances in basic science, pharmacology, surgery, and technology, progress in lifestyle improvements, now considered essential, has been disappointing. Patient adherence to medications and other instructions play the greatest role in individual outcome shortfalls. Classically medicine has approached management using a high-risk model, targeting clinical manifestations of disease with progressively intensive therapies, in contrast with population-based models. In an effort to identify effectiveness among the many models available, the "pathways model" is reevaluated. METHODS: Relying upon secondary data from prior studies in which Papanicolaou (Pap) test utilization was successfully improved, a "pathway model" is qualitatively reexamined in which characteristics of patients, providers, and the health system-as impacted by culture, beliefs, values, and habits-are acknowledged and incorporated by community resources into treatment plans. In so doing, health disparities are also addressed. OBSERVATIONS: The culturally inclusive pathways model using immersion community-based participation was successful in modifying behaviors when applied to a high-risk population in great need of improving Pap test adherence. CONCLUSIONS: In populations characterized by recognized cultural barriers contributing to low adherence, the pathways model may improve chronic disease outcomes. This model emphasizes a high degree of immersion within a culture and community as vehicles to improve patient behavior and address inequities. Central features are concordant with current concepts in guidelines, scientific statements, manuals, and advisories concerning the conduct of community-based research and social determinants of health. The pathways model deserves consideration for use in other chronic illnesses, such as cardiometabolic disease.

Cultural primer for cardiometabolic health: health disparities, structural factors, community, pathways to improvement, and clinical applications.

The quest to optimize cardiometabolic health has created great interest in nonmedical health variables in the population, community-based research and coordination, and addressing social, ethnic, and cultural barriers. All of these may be of equal or even greater importance than classical health care delivery in achieving individual well-being. One dominant issue is health disparity - causes, methods of reduction, and community versus other levels of solutions. This communication summarizes some major views regarding social structures, followed by amplification and synthesis of central ideas in the literature. The role of community involvement, tools, and partnerships is also presented in this Primer. Recent views of how these approaches could be incorporated into cardiometabolic initiatives and strategies follow, with implications for research. Two examples comparing selected aspects of community leverage and interventions in relation to individual approaches to health care equity are examined in depth: overall performance in reducing cardiovascular risk and mortality, and the recent National Diabetes Prevention Program, both touching upon healthy diets and adherence. Finally, the potential that precision medicine offers, and possible effects on disparities are also discussed.

n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: Principles, Practices, Pitfalls, and Promises - A Contemporary Review.

Amidst voluminous literature, inconsistencies and opposing results have confused rather than clarified cardiologists' ability to assess the potential benefits of n-3 polyunsaturated fatty acids (n-3 PUFA). In perspective, there are common themes that emerge from n-3 PUFA studies, even as imperfect as they may be. The approach taken was to identify and unite these themes into a manageable, cohesive, evidence-based, yet useful synthesis. In all reviews and meta-analyses, the selection of component studies and assumptions influences outcomes. This overarching principle must be combined with the totality of the data, particularly when evidence is incompletely understood and gaps in knowledge must be bridged. Both the older literature and the most recent rigorous meta-analyses indicate that n-3 PUFA are highly pleiotropic agents with many documented positive physiological effects. Concordance among preclinical, observational, randomized clinical trials and meta-analyses is impressive. These agents have modest, statistically significant benefits which accrue over time. Given their favorable safety profile, a risk reduction of about 10% justifies their potential use in cardiovascular disease.

A User-Centered Glucose-Insulin Data Display for the Inpatient Setting.

Inpatient management of insulin-dependent diabetes (IDD) is a complex task that requires clinicians to cognitively process information across distinct domains in different locations of the electronic medical record (EMR). Current data displays are not optimized to support insulin management by end users. We sought to develop a set of user-centered displays of capillary glucose data and insulin dose to improve inpatient management of IDD. Our proposed conceptual data display prototype is designed to simplify the presentation and visualization of key information needed for treatment decisions. The goal is also to enhance clinician's ability to identify opportunities to optimize insulin dosing and decrease end users' cognitive load and error rates.

Cardiometabolic diseases of civilization: history and maturation of an evolving global threat. An update and call to action.

Despite striking extensions of lifespan, leading causes of death in most countries now constitute chronic, degenerative diseases which outpace the capacity of health systems. Cardiovascular disease is the most common cause of death in both developed and undeveloped countries. In America, nearly half of the adult population has at least one chronic disease, and polypharmacy is commonplace. Prevalence of ideal cardiovascular health has not meaningfully improved over the past two decades. The fall in cardiovascular deaths in Western countries, half due to a fall in risk factors and half due to improved treatments, have plateaued, and this reversal is due to the dual epidemics of obesity and diabetes type 2. High burdens of cardiovascular risk factors are also evident globally. Undeveloped nations bear the burdens of both infectious diseases and high childhood death rates. Unacceptable rates of morbidity and mortality arise from insufficient resources to improve sanitation, pure water, and hygiene, ultimately linked to poverty and disparities. Simultaneously, about 80% of cardiovascular deaths now occur in low- and middle-income nations. For these reasons, risk factors for noncommunicable diseases, including poverty, health illiteracy, and lack of adherence, must be targeted with unprecedented vigor worldwide. Key messages In developed and relatively wealthy countries, chronic "degenerative" diseases have attained crisis proportions that threaten to reverse health gains made within the past decades. Although poverty, disparities, and poor sanitation still cause unnecessary death and despair in developing nations, they are now also burdened with increasing cardiovascular mortality. Poor adherence and low levels of health literacy contribute to the high background levels of cardiovascular risk.

Stable Ischemic Heart Disease.

Classical angina refers to typical substernal discomfort triggered by effort or emotions, relieved with rest or nitroglycerin. The well-accepted pathogenesis is an imbalance between oxygen supply and demand. Goals in therapy are improvement in quality of life by limiting the number and severity of attacks, protection against future lethal events, and measures to lower the burden of risk factors to slow disease progression. New pathophysiological data, drugs, as well as conceptual and technological advances have improved patient care over the past decade. Behavioral changes to improve diets, increase physical activity, and encourage adherence to cardiac rehabilitation programs, are difficult to achieve but are effective.

Current Treatment of Dyslipidemia: Evolving Roles of Non-Statin and Newer Drugs.

Since their introduction, statin (HMG-CoA reductase inhibitor) drugs have advanced the practice of cardiology to unparalleled levels. Even so, coronary heart disease (CHD) still remains the leading cause of death in developed countries, and is predicted to soon dominate the causes of global mortality and disability as well. The currently available non-statin drugs have had limited success in reversing the burden of heart disease, but new information suggests they have roles in sizeable subpopulations of those affected. In this review, the status of approved non-statin drugs and the significant potential of newer drugs are discussed. Several different ways to raise plasma high-density lipoprotein (HDL) cholesterol (HDL-C) levels have been proposed, but disappointments are now in large part attributed to a preoccupation with HDL quantity, rather than quality, which is more important in cardiovascular (CV) protection. Niacin, an old drug with many antiatherogenic properties, was re-evaluated in two imperfect randomized controlled trials (RCTs), and failed to demonstrate clear effectiveness or safety. Fibrates, also with an attractive antiatherosclerotic profile and classically used for hypertriglyceridemia, lacks evidence-based proof of efficacy, save for a subgroup of diabetic patients with atherogenic dyslipidemia. Omega-3 fatty acids fall into this category as well, even with an impressive epidemiological evidence base. Omega-3 research has been plagued with methodological difficulties yielding tepid, uncertain, and conflicting results; well-designed studies over longer periods of time are needed. Addition of ezetimibe to statin therapy has now been shown to decrease levels of low-density lipoprotein (LDL) cholesterol (LDL-C), accompanied by a modest decrease in the number of CV events, though without any improvement in CV mortality. Importantly, the latest data provide crucial evidence that LDL lowering is central to the management of CV disease. Of drugs that inhibit cholesteryl ester transfer protein (CETP) tested thus far, two have failed and two remain under investigation and may yet prove to be valuable therapeutic agents. Monoclonal antibodies to proprotein convertase subtilisin/kexin type 9, now in phase III trials, lower LDL-C by over 50 % and are most promising. These drugs offer new ability to lower LDL-C in patients in whom statin drug use is, for one reason or another, limited or insufficient. Mipomersen and lomitapide have been approved for use in patients with familial hypercholesterolemia, a more common disease than appreciated. Anti-inflammatory drugs are finally receiving due attention in trials to elucidate potential clinical usefulness. All told, even though statins remain the standard of care, non-statin drugs are poised to assume a new, vital role in managing dyslipidemia.

Current Treatment of Dyslipidemia: A New Paradigm for Statin Drug Use and the Need for Additional Therapies.

Coronary heart disease (CHD) is the leading cause of death in most countries, with the high prevalence currently driven by dual epidemics of obesity and diabetes. Statin drugs, the most effective, evidence-based agents to prevent and treat this disease, have a central role in management and are advised in all published guidelines. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol and assessment guidelines ('new ACC/AHA guidelines') emphasized global cardiovascular (CV) risk reduction as opposed to targeting low-density lipoprotein-cholesterol (LDL-C) levels, stressed the use of statins in two dose intensities, utilized a new risk calculator using pooled cohort equations, and lowered the risk cutoff for initiation of statin therapy. Although there were major strengths of the new ACC/AHA guidelines, substantial controversy followed their release, particulars of which are discussed in this review. They were generally regarded as improvements in an ongoing transition using evidenced-based data for maximum patient benefit. Several guidelines, other than the ACC/AHA guidelines, currently provide practitioners with choices, some depending on practice locations. Cholesterol control with statin drugs is used in all paradigms. However, some patients respond inadequately, approximately 15% are intolerant, and other factors prevent attaining cholesterol goals in as many as 40% of patients. Even after treatment, substantial residual risk for ongoing major events remains. Another readily available modality that can rival statin drugs in effectiveness is vast improvement in diet and lifestyle within the general population; however, despite great effort, existing programs to implement such changes have failed. Hence, despite unrivaled success, there is great need for additional drugs to prevent and treat CHD, whether as monotherapy or in combination with statin drugs. New American guidelines do not discuss or recommend any nonstatin drugs for CHD, and the US FDA has moved away from approving drugs based solely on changes in surrogates in the absence of clinical outcomes trials. Both have significantly altered the realities of developing pharmacotherapies and cardiology practice.

Cardiovascular prevention: components, levels, early origins, and metrics.

This article presents core epidemiological studies that establish the basis for cardiovascular prevention strategies. The results of the classic INTERHEART and INTERSTROKE studies that delineated population-attributed risk for myocardial infarction and stroke are described. Differences in the levels or types of prevention-primordial, primary, and secondary-lead to the concept that risk occurs on a continuum throughout life with great variability, beginning in infancy. Any meaningful and sustained reduction in cardiovascular risk must begin in childhood, as habits formed early in life have an impact for decades. Although it is never too late to improve unhealthy habits, interventions early in life are more likely to be effective in preventing disease from developing, in delaying manifestations, or in reversing pathology through evidence-based therapies that are applied later. There is compelling evidence that coronary atherosclerosis, heart disease related to diabetes, and hypertension begin with endothelial activation. Oxidative stress and reduced nitric oxide availability are also among the earliest of events, from which a self-amplifying web of events proceed. The American Heart Association, even prior to its now-validated and classic definition of risk metrics, developed a strategic plan to improve health habits in the population and at the community level for promoting and monitoring behavior change and patients' self-reported health status. Other initiatives for improving cardiovascular health are in place as well. Despite improvements in treatment of risk factors, there has been minimal, if any, success in reversing the dual epidemics of obesity and diabetes. These 2 factors continue to drive the high burden of cardiovascular risk, and now lead current public health issues. Because treatment alone cannot fully address this tsunami of risk, it has been suggested that all physicians assume an unprecedented and aggressive role as advocates for behavior change to prevail against the foes of obesity and diabetes.

Stable ischemic heart disease.

Classical angina refers to typical substernal discomfort triggered by effort or emotions, relieved with rest or nitroglycerin. The well-accepted pathogenesis is an imbalance between oxygen supply and demand. Goals in therapy are improvement in quality of life by limiting the number and severity of attacks, protection against future lethal events, and measures to lower the burden of risk factors to slow disease progression. New pathophysiological data, drugs, as well as conceptual and technological advances have improved patient care over the past decade. Behavioral changes to improve diets, increase physical activity, and encourage adherence to cardiac rehabilitation programs, are difficult to achieve but are effective.

Exclusion of 'nonRCT evidence' in guidelines for chronic diseases - is it always appropriate? The Look AHEAD study.

Evidence-based medicine (EBM) is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. The introduction of EBM was a conceptual and practical milestone in the history of medicine, with far-reaching impact yet to be fully realized. EBM has limitations, including inapplicability to populations dissimilar to those in studies, and may not reflect duration of exposure to risk factors, details of lifestyle, incubation period, latency, or environmental changes during chronic diseases. Routine exclusion of evidence other than randomized controlled trials (RCTs) or meta-analyses from consideration in treatment may not always be wise. This review is not a result of a search, but rather a conceptual unification of (a) the increasing restrictions in guideline-writing favoring more RCTs, and rejecting observational studies when chronic diseases with a long incubation period may sometimes be best probed by the latter; (b) the possibility RCTs may be inconclusive, nonapplicable, or result in 'negative' results which may misdirect future therapy by physicians and undermine adherence by patients; (c) the potential improvement in patient care from having all available information evaluated (especially epidemiological studies of chronic diseases) and synthesized in guidelines. The example of the Look AHEAD study is chosen - a 'negative' RCT with significant information overlooked by reviewers, who initially declared that weight loss and physical activity were ineffective in treating diabetes, or in preventing cardiovascular complications. In this review, placing this study in perspective, among others, suggests the opposite - exercise and weight loss are effective if done early and sufficiently. Synthesizing worthy data from many sources, including prospective and pathophysiological studies, particularly when RCTs are unavailable, has the potential to add depth and expand the understanding of disease. In addition, integrated data may generate useful, rich material for use during shared decision making discussions with patients, and clarify future hypotheses.

Prevention of cardiovascular disease: updating the immensity of the challenge and the role of risk factors.

Despite remarkable decreases in the mortality of coronary heart disease, there is concern that continued high levels of cardiovascular risk in the population may reverse these gains. By 2015, the prevalence of cardiovascular disease in the United States will be 37.8%. Obesity, hypertension, dyslipidemia, diabetes mellitus (DM), metabolic syndrome, and inflammation are the primary components driving cardiovascular risk. Approximately 70% of adults are overweight or obese, yet diet quality continues to deteriorate and authoritative information is insufficiently promoted. More than half of US adults have lipid abnormalities; 27% of US adults have high values of low-density lipoprotein cholesterol, 23% have low values of high-density lipoprotein cholesterol concentrations, and 30% have high triglyceride levels. Approximately 34% of adults have hypertension; 40% of these adults are unaware of the diagnosis. In patients with hypertension who are treated, 54% remain uncontrolled. The prevalence of hypertension in elderly patients has increased from 35% to 41%. In addition, 30% of adults have prehypertension. The burden of hypertension alone accounts for approximately 1000 deaths per day. Trends in the prevalence of glucose intolerance are similar. The prevalence of DM is approximately 12%, with 27% of cases remaining undiagnosed. Thirty-five percent of US adults aged > 20 years have prediabetes and 7.3% of adults are unaware of the diagnosis. If the present trends continue, 1 in 3 of US adults will have DM by 2050. Participation in exercise has been low and a "straight line" for > 2 decades. Accelerometer data indicate that individuals who attain minimal exercise goals are only a fraction of the often quoted levels of > 35%. Control of risk factors in primary prevention, although improved, remains decidedly incomplete. Lowering the burden of cardiovascular risk factors at the population level has been exceptionally difficult. For reasons outlined, the solution to this problem is multifaceted and extends well beyond the delivery of medical care into the structure of society and the environment.