Effects of Alpha-hydroxy-isocaproic acid upon Body Composition in a Type I Diabetic Patient with Muscle Atrophy - A Case Study.

Research involving dietary supplement interventions for sarcopenia and osteopenia in type 1 diabetes patients is scarce. Here we present a case study of a type 1 diabetic patient that was treated with supplemental alpha-hydroxy-isocaproic acid (α-HICA) for 120 days. Several measures of body composition by dual x-ray absorptiometry, blood markers, and maximum voluntary contraction parameters were assessed at baseline and after 120 days. The patient's baseline weight was 73.2 kg, which increased to 75.2 kg by the 120-day assessment. Salient mass distribution changes included increases of trunk fat mass (+0.4 kg), trunk fat free mass (+0.2 kg), total trunk mass (+0.2 kg), and a decrease of 8 percent in trunk fat mass contribution. Handgrip strength increased by 58.84 N, whereas isometric force in the leg press decreased by 347.15 N. Amelioration of BMD Z-scores from -0.7 to 0.5 and T-scores from -1.0 to -0.9 were noted. Importantly, full hematologic measures and weekly nutritional counselling assessments revealed no signs of adverse effects with α-HICA supplementation. Due to the imperative of maintaining FFM, strength and bone mass in these patients, additional research is necessary to confirm these promising results and to clarify whether leucine and/or one of its derivatives might be clinically useful.

"Calories in, calories out" and macronutrient intake: the hope, hype, and science of calories.

One of the central tenets in obesity prevention and management is caloric restriction. This perspective presents salient features of how calories and energy balance matter, also called the "calories in, calories out" paradigm. Determinants of energy balance and relationships to dietary macronutrient content are reviewed. The rationale and features of the carbohydrate-insulin hypothesis postulate that carbohydrate restriction confers a metabolic advantage. According to this model, a large amount of fat intake is enabled without weight gain. Evidence concerning this possibility is detailed. The relationship and application of the laws of thermodynamics are then clarified with current primary research. Strong data indicate that energy balance is not materially changed during isocaloric substitution of dietary fats for carbohydrates. Results from a number of sources refute both the theory and effectiveness of the carbohydrate-insulin hypothesis. Instead, risk for obesity is primarily determined by total calorie intake.

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.

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.

Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular risk.

Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery endothelial function, in a cohort of patients at increased cardiovascular (CV) risk. The present cross-sectional study included 247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and the saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 % carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1.66 (sd 0.41) v. 1.52 (sd 0.22), P= 0.037). These results were particularly strong in patients with the MS (Q1 = 1.82 (sd 0.32) v. Q4 = 1.61 (sd 027); P= 0.021) and T2D (Q1 = 1.78 (sd 0.31) v. Q4 = 1.62 (sd 0.35); P= 0.011). Multivariate analysis demonstrated that individuals in the highest LCDS quartile had a significantly negative coefficient of saRHI, which was independent of confounders (OR -0.85; 95 % CI 0.19, 0.92; P= 0.031). These findings suggest that a dietary pattern characterised by a low amount of carbohydrate, but high amounts of protein and fat, is associated with a poorer small artery vascular reactivity in patients with increased CV risk.

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.

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.

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.

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.

Clinical Perspective on Antihypertensive Drug Treatment in Adults With Grade 1 Hypertension and Low-to-Moderate Cardiovascular Risk: An International Expert Consultation.

Hypertension is a leading risk factor for disease burden globally. An unresolved question is whether grade 1 hypertension (140-159/90-99mmHg) with low (cardiovascular mortality <1% at 10 years) to moderate (cardiovascular mortality ≥1% and <5% at 10 years) absolute total cardiovascular risk (CVR) should be treated with antihypertensive agents. A virtual international consultation process was undertaken to summarize the opinions of select experts. After holistic analysis of all epidemiological, clinical, psychosocial, and public health elements, this consultation process reached the following consensus in hypertensive adults aged <80 years: (1) The question of whether drug treatment in grade 1 should be preceded by a period of some weeks or months during which only lifestyle measures are recommended cannot be evidence based, but the consensus opinion is to have a period of lifestyle alone reserved only to patients with grade 1 "isolated" hypertension (grade 1 uncomplicated hypertension with low absolute total CVR, and without other major CVR factors and risk modifiers). (2) The initiation of antihypertensive drug therapy in grade 1 hypertension with moderate absolute total CVR should not be delayed. (3) Men ≥55 years and women ≥60 years with uncomplicated grade 1 hypertension should automatically be classified within the moderate absolute total CVR category, even in the absence of other major CVR factors and risk modifiers. (4) Statins should be considered along with blood-pressure lowering therapy, irrespective of cholesterol levels, in patients with grade 1 hypertensive with moderate CVR.

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.

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.

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.

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.

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.