James O'Keefe

University of Missouri - Kansas City | UMKC · Department of Internal Medicine

Statins are first-line therapy for treating dyslipidemia because of their low-density lipoprotein cholesterol (LDL-C) lowering efficacy, superior event-reduction data and unrivaled cost-effectiveness. Yet, many people are intolerant of statins, whether due to true adverse events or the nocebo effect, so within one year about two-thirds of primary p...

The deacetylase sirtuin 1 (Sirt1), activated by calorie restriction and fasting, exerts several complementary effects on cellular function that are favourable to healthspan; it is often thought of as an ‘anti-aging’ enzyme. Practical measures which might boost Sirt1 activity are therefore of considerable interest. A number of nutraceuticals have po...

Oxidative and dicarbonyl stress, driven by excess accumulation of glycolytic intermediates in cells that are highly permeable to glucose in the absence of effective insulin activity, appear to be the chief mediators of the complications of diabetes. The most pathogenically significant dicarbonyl stress reflects spontaneous dephosphorylation of glyc...

Vegan diets are widely promoted as protective against cardiovascular disease (CVD); however, removing all animal foods from a human's diet usually causes unfavorable health consequences. Our hominin ancestors began consuming meat, fish, seafood, and eggs >2 million years ago. Consequently, humans are genetically adapted to procure nutrients from bo...

Regular exercise confers multifaceted and well-established health benefits. Yet, transient and asymptomatic increases in markers of cardio-renal injury are commonly observed in ultra-endurance athletes during and after competition. This has raised concerns that chronic recurring insults could cause long-term cardiac and/or renal damage. Indeed, ext...

An adequate intake of dietary protein is critical to human health and, as a result, protein is the only macronutrient with a recommended daily allowance. Yet, compared to fat and carbohydrate sources, the impact of dietary protein sources on human and cardiovascular health has received far less attention. However, consistent data from large prospec...

For reasons that remain unclear, endogenous synthesis and tissue levels of coenzyme Q10 (CoQ10) tend to decline with increasing age in at least some tissues. When CoQ10 levels are sufficiently low, this compromises the efficiency of the mitochondrial electron transport chain, such that production of superoxide by site 2 increases and the rate of ad...

Ferulic acid, a bacterial metabolite of anthocyanins, seems likely to be a primary mediator of the health benefits associated with anthocyanin-rich diets, and has long been employed in Chinese cardiovascular medicine. In rodent studies, it has exerted wide-ranging antioxidant and anti-inflammatory effects, the molecular basis of which remains rathe...

For over 40 years saturated fat, the fat found primarily in animal foods, was thought to be the main culprit for increasing cholesterol levels and causing heart disease. During this same time vegetable oils were promoted as being heart healthy because they could lower cholesterol. However, recently the evidence implicating saturated fat as being ha...

Background Cardiovascular and kidney complications of T2D are increasing, in part due to suboptimal implementation of guideline-directed therapies. The Saint Luke's Haverty Cardiometabolic Center (CMC) of Excellence implements team-based, patient-centered approach focused on comprehensive risk reduction for patients with T2D and CVD, including use...

This is the french traduction of: @article{dinicolantonio2018sugar, title={Sugar addiction: is it real? A narrative review}, author={DiNicolantonio, James J and O’Keefe, James H and Wilson, William L}, journal={British journal of sports medicine}, volume={52}, number={14}, pages={910--913}, year={2018}, publisher={BMJ Publishing Group Ltd and Briti...

Background: Data regarding the use of GLP-1 receptor agonists (GLP-1RA) in patients with established heart failure (HF) remain limited. Methods: We included patients with established HF treated at Cardiometabolic Center (CMC) between January 2019 and December 2020 who had at least two visits and received GLP-1RA. We compared change in outcomes of i...

Estradiol (E2) plays an underrecognized role in modulating body-wide systems, including important interactions with the renin-angiotensin-aldosterone system (RAAS). The RAAS is an immunomodulating system that is critical for maintaining homeostasis across multiple organ systems. The diverse interactions between E2 and the RAAS help maintain cardiom...

Common nuts (tree nuts and peanuts) are energy-dense foods that nature has gifted with a complex matrix of beneficial nutrients and bioactives, including monounsaturated and polyunsaturated fatty acids, high-quality protein, fiber, non-sodium minerals, tocopherols, phytosterols, and antioxidant phenolics. These nut components synergize to favorably...

Background Individuals living in the same household are exposed to common risk factors. We hypothesized that living with someone who has fatty liver disease increases the risk of having the same disease. Methods This was a retrospective study that included pairs of men and women who shared the same residential addresses, underwent screening non-con...

Cardiovascular (CV) disease (CVD) remains the leading cause of major morbidity and CVD- and all-cause mortality in most of the world. It is now clear that regular physical activity (PA) and exercise training (ET) induces a wide range of direct and indirect physiologic adaptations and pleiotropic benefits for human general and CV health. Generally,...

Atrial fibrillation (AF) is the most common clinically significant arrhythmia, and it increases stroke risk. A preventive approach to AF is needed because virtually all treatments such as cardioversion, antiarrhythmic drugs, ablation, and anticoagulation are associated with high cost and carry significant risk. A systematic review was performed to...

Objective To investigate the association between the duration of weekly leisure-time sports activity and all-cause mortality. Methods As part of the prospective Copenhagen City Heart Study, 8697 healthy adults completed a comprehensive questionnaire about leisure-time sports activities. Duration (minutes per week) of leisure-time sports activities...

Over the past decade there has been a considerable debate whether fish oil supplementation works to prevent and/or treat cardiovascular disease. This is due to the fact that previous studies testing fish oil in Italy and Japan found significant reductions in all-cause mortality, sudden cardiac death, and cardiovascular events, whereas more recent s...

Periodontal disease (PD) is common in the US and globally. Evidence suggests that poor oral health is associated with atherosclerotic cardiovascular disease (ASCVD); however, this relationship has not been a major focus in clinical cardiology. This manuscript will review the growing evidence linking PD to ASCVD, including pathophysiologic mechanism...

Postmenopausal (PM) hormone therapy (HT) was extremely popular for years as a treatment for many conditions, including cardiovascular (CV) disease (CVD) prevention. The adverse results from the Women’s Health Initiative (WHI) ended the widespread prescriptive use of HT for nearly 20 years. The WHI findings have been broadly and unfairly applied to...

Type 2 diabetes mellitus (T2D) is a common comorbidity among patients who have undergone heart transplantation. Recently two classes of glucose-lowering medications (SGLT-2Is and GLP-1RAs), have been shown to significantly improve cardiovascular outcomes. There is a paucity of data regarding their use in immunosuppressed patients, with many studies...

Interest in the potential cardiovascular (CV) benefits of omega-3 polyunsaturated fatty acids (Ω-3) began in the 1940s and was amplified by a subsequent landmark trial showing reduced CV disease (CVD) risk following acute myocardial infarction. Since that time, however, much controversy has circulated due to discordant results among several studies...

Magnesium and vitamin D each have the possibility of affecting the immune system and consequently the cytokine storm and coagulation cascade in COVID-19 infections. Vitamin D is important for reducing the risk of upper respiratory tract infections and plays a role in pulmonary epithelial health. While the importance of vitamin D for a healthy immun...

Up until about 100 years ago, the omega-6/3 ratio has been around 4:1 or less. However, the typical Western diet now provides an omega-6/3 ratio of approximately 20:1 in favor of omega-6. This predisposes to supraphysiologic inflammatory responses and perpetuates chronic low-grade inflammation. The overconsumption of linoleic acid, mainly from indu...

Inflammasomes are intracellular protein complexes that form in response to a variety of stress signals and that serve to catalyze the proteolytic conversion of pro-interleukin-1β and pro-interleukin-18 to active interleukin-1β and interleukin-18, central mediators of the inflammatory response; inflammasomes can also promote a type of cell death kno...

Takotsubo syndrome (TTS), also known as stress cardiomyopathy and broken heart syndrome, is a neurocardiac condition that is among the most dramatic manifestations of psychosomatic disorders. This paper is based on a systematic review of TTS and stress cardiomyopathy using a PubMed literature search. Typically, an episode of severe emotional or phy...

Vasculogenic erectile dysfunction has been aptly called the “canary in the coal mine” for cardiovascular disease as it almost always precedes other manifestations of atherosclerotic cardiovascular disease, including myocardial infarction and stroke. It is common, associated with the presence of modifiable cardiovascular risk factors, and impacted b...

Inflammatory cytokine storms in the lungs are a potential consequence of RNA viruses. One issue that may increase the risk of developing inflammatory cytokine storms in the lungs during viral infections is an imbalance in the dietary omega-6/3 ratio. Indeed, over the past 100 years the omega-6/3 ratio in the Western world has increased from approxi...

Background: Alzheimer's disease (AD) is increasingly prevalent and over 99% of drugs developed for AD have failed in clinical trials. A growing body of literature suggests that potent inhibitors of tumor necrosis factor-α (TNF-α) have potential to improve cognitive performance. Objective: In this review, we summarize the evidence regarding the p...

As opportunistic omnivores, humans are evolutionarily adapted to obtain calories and nutrients from both plant and animal food sources. Today, many people overconsume animal products, often-processed meats high in saturated fats and chemical additives. Alternatively, strict veganism can cause nutritional deficiencies and predispose to osteopenia, s...

There is a bidirectional link between diabetes and heart failure (HF). HF occurs in individuals with diabetes at higher rates, even in the absence of other HF risk factors such as coronary artery disease and hypertension. Patients with HF are also at risk of developing incident diabetes over time. The high prevalence of ischemic heart disease and c...

Most of the global population is deficient in long-chain marine omega-3s. In particular, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for brain and eye development. Additionally, DHA plays a significant role in mental health throughout early childhood and even into adulthood. In the brain, DHA is important for cellular...

Although the prevalence of attention-deficit/hyperactivity disorder (ADHD) has been stable over the past 3 decades, prescriptions of sympathomimetic stimulants have steadily increased in the United States. This study consisted of a systematic review of PubMed articles screened for ADHD medications and potential cardiovascular toxicity as well as no...

A wealth of scientific literature backs the unique therapeutic benefits of exercise for quality of life, cardiovascular (CV) health, and longevity. Consequently, many have assumed that more exercise is always better. However, chronic excessive endurance exercise might adversely impact CV health. Ultra-endurance races can inflict acute myocardial da...

Background Multi-societal consensus recommendations endorse both planar and single photon emission tomographic (SPECT) image acquisitions for the evaluation of cardiac amyloidosis. However, the correlation between planar and SPECT findings and the optimal timing of image acquisitions remain uncertain.Methods This is an analysis of 109 consecutive p...

Background: Optimal guideline-directed medical therapy is delivered to only 6.9% of patients with type 2 diabetes (T2D) and cardiovascular disease (CVD) nationally, despite guideline recommendations emphasizing aggressive comprehensive secondary risk reduction. While there are many potential explanations, lack of effective clinical care delivery mo...

In the United States, cardiovascular disease (CVD) is the leading cause of death and disability. Suboptimal diet quality is responsible for a greater percentage of CVD-related morbidity and mortality than any other modifiable risk factor. Further troubling are the stark racial/ethnic and socioeconomic disparities in diet quality. This represents a...

The presence of hypertension (HTN) in patients with diabetes mellitus (DM) further worsens cardiovascular disease (CVD) prognosis. In addition, masked HTN and abnormal circadian blood pressure (BP) variability are common among patients with DM. Clinical trial data show that sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve CVD prognosis an...

Insulin, either in its intravenous or subcutaneous forms, remains the standard therapy for virtually all type-1 diabetes and many of the type-2 diabetes patients in its advanced stages. With advancement of injection techniques, insulin therapy has become much more patient- friendly than ever. Still there is vast area of unmet needs regarding curren...

Spirulina, a cyanobacteria commonly referred to as a blue-green algae, is one of the oldest lifeforms on Earth. Spirulina grows in both fresh and saltwater sources and is known for its high protein and micronutrient content. This review paper will cover the effects of spirulina on weight loss and blood lipids. The currently literature supports the...

The majority of acute coronary syndromes are caused by the rupture of plaques rendered vulnerable by oxidized lipids, inflammation, and a thin fibrous cap with reduced collagen and smooth muscle cell content.2 Thus, stabilizing and reversing vulnerable atherosclerotic plaques can help to prevent cardiovascular events. In this regard, long-chain ome...

Recently, 3 large randomized controlled trials (RCTs) have assessed the effects of supplementation with marine omega-3 fatty acids on the occurrence of cardiovascular disease (CVD) events. We reviewed this evidence and considered it in the context of the large and growing body of data on the CV health effects of marine omega-3s. One RCT examining 8...

There has been a raging debate whether marine omega-3s are effective for the prevention of cardiovascular disease. Our review paper discusses the landmark clinical studies testing the benefits of marine omega-3s. Moreover, for the first time, the REDUCE-IT study tested a high dose of marine omega-3s (4 grams of icosapent ethyl per day) on top of st...

Type 2 Diabetes (T2D) is a growing public health threat that is evolving into a global pandemic with debilitating, expensive and often lethal complications. Even when hemoglobin A1c (HbA1C) levels are well controlled, and concomitant cardiovascular (CV) risk factors are effectively treated, two out of every three patients with T2D are destined to d...

The gaseous physiological modulator hydrogen sulfide (H2S) has recently been shown to exert a variety of neuroprotective effects. In particular, the treatment of transgenic mouse models of Alzheimer's disease (AD) with agents that release H2S aids preservation of cognitive function, suppresses brain production of amyloid beta, and decreases tau pho...

Physical inactivity and psychosocial stress are prevalent in residents of the United States. The purpose of this article is to review the interaction between these 2 conditions and examine the effects of exercise on stress and cardiovascular (CV) health. A query of scientific references between 1974 to 2018 was performed using the PubMed search eng...

The terms “prevention” and “risk reduction” are often used interchangeably in medicine. There is considerable debate, however, over the use of these terms in describing interventions that aim to preserve cognitive health and/or delay disease progression of Alzheimer's disease (AD) for patients seeking clinical care. Furthermore, it is important to...

Background: Evidence suggests that the overconsumption of added sugars can induce fatty liver disease and insulin resistance. Aim: To propose a hypothesis that added sugars induce copper deficiency which can lead to hepatic iron overload, fatty liver disease, insulin resistance and eventually non-alcoholic steatohepatitis. Setting: On average, th...

Objective: To evaluate the differential improvements in life expectancy associated with participation in various sports. Patients and methods: The Copenhagen City Heart Study (CCHS) is a prospective population study that included detailed questionnaires regarding participation in different types of sports and leisure-time physical activity. The...

Salt has notoriously been blamed for causing an increase in the urinary excretion of calcium and thus is considered to be a risk factor for osteoporosis. However, the increase in the urinary excretion of calcium with higher sodium intakes can be offset by the increased intestinal absorption of dietary calcium. Thus, the overall calcium balance does...

Nonalcoholic fatty liver disease (NAFLD) is becoming common in the United States and throughout the world and can progress to cirrhosis, hepatocellular carcinoma, and death. There is a strong association between coronary artery disease and NAFLD due to common risk factors, such as metabolic syndrome, obesity, and diabetes mellitus. Subclinical athe...

The potential cardiovascular (CV) benefits of many trending foods and dietary patterns are still incompletely understood, and scientific inquiry continues to evolve. In the meantime, however, a number of controversial dietary patterns, foods, and nutrients have received significant media attention and are mired by “hype.” This second review address...