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Managing folate deficiency implies filling the gap between laboratory and clinical assessment.
Ferraro, S, Biganzoli, G, Gringeri, M, Radice, S, Rizzuto, AS, Carnovale, C, Biganzoli, EM, Clementi, E
Clinical nutrition (Edinburgh, Scotland). 2022;(2):374-383
Abstract
The characterization of folate status in subjects at risk of deficiency and with altered vitamin homeostasis is crucial to endorse preventive intervention health policies, especially in developed countries. Several physiological changes (i.e. pregnancy), clinical situations and diseases have been associated to increased requirement, impaired intake and absorption of folate. However clinical practice guidelines (CPG) endorse folic acid supplementation generally discarding the use of its determination in serum to assess the risk of deficiency and/or its concentration at baseline. Poor confidence on the diagnostic accuracy of serum folate assays still persists in the current CPGs although recent standardization efforts have greatly improved inter-method variability and precision. In this review we critically appraise the methodological issues concerning laboratory folate determination and the evidence on the potential adverse effects of folic acid exposure. The final aim is to build a sound background to promote serum folate-based cost-effective health care policies by optimizing folic acid supplementation in subjects at risk of deficiency and with altered folate homeostasis. Our first result was to adjust in relation to current serum folate assays the thresholds reported by CPGs as index of folate status, defined on the association with metabolic and hematologic indicators. We identify a statistically significant difference between the estimated thresholds and accordingly show that the assessment of folate status actually changes in relation to the assay employed. The use of the method-dependent thresholds here reported may pragmatically endorse the stewardship of folic acid supplementation in clinical practice and increase the cost-effectiveness of health care policies.
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Hiding unhealthy heart outcomes in a low-fat diet trial: the Women's Health Initiative Randomized Controlled Dietary Modification Trial finds that postmenopausal women with established coronary heart disease were at increased risk of an adverse outcome if they consumed a low-fat 'heart-healthy' diet.
Noakes, TD
Open heart. 2021;(2)
Abstract
The Women's Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT) was designed to test whether the US Department of Agriculture's 1977 Dietary Guidelines for Americans protects against coronary heart disease (CHD) and other chronic diseases. The only significant finding in the original 2006 WHIRCDMT publication was that postmenopausal women with CHD randomised to a low-fat 'heart-healthy' diet in 1993 were at 26% greater risk of developing additional CHD events compared with women with CHD eating the control diet. A 2017 WHIRCDMT publication includes data for an additional 5 years of follow-up. It finds that CHD risk in this subgroup of postmenopausal women had increased further to 47%-61%. The authors present three post-hoc rationalisations to explain why this finding is 'inadmissible': (1) only women in this subgroup were less likely to adhere to the prescribed dietary intervention; (2) their failure to follow the intervention diet increased their CHD risk; and (3) only these women were more likely to not have received cholesterol-lowering drugs. These rationalisations appear spurious. Rather these findings are better explained as a direct consequence of postmenopausal women with features of insulin resistance (IR) eating a low-fat high-carbohydrate diet for 13 years. All the worst clinical features of IR, including type 2 diabetes mellitus (T2DM) in some, can be 'reversed' by the prescription of a high-fat low-carbohydrate diet. The Women's Health Study has recently reported that T2DM (10.71-fold increased risk) and other markers of IR including metabolic syndrome (6.09-fold increased risk) were the most powerful predictors of future CHD development in women; blood low-density lipoprotein-cholesterol concentration was a poor predictor (1.38-fold increased risk). These studies challenge the prescription of the low-fat high-carbohydrate heart-healthy diet, at least in postmenopausal women with IR, especially T2DM. According to the medical principle of 'first do no harm', this practice is now shown to be not evidence-based, making it scientifically unjustifiable, perhaps unethical.
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Recent Updates on Vascular Complications in Patients with Type 2 Diabetes Mellitus.
Jung, CH, Mok, JO
Endocrinology and metabolism (Seoul, Korea). 2020;(2):260-271
Abstract
It is well known that patients with type 2 diabetes mellitus (T2DM) are at an increased risk of morbidity and mortality from atherosclerotic cardiovascular (CV) complications. Previously, the concept that diabetes mellitus (DM) is a "coronary artery disease (CAD) risk equivalent" was widely accepted, implying that all DM patients should receive intensive management. However, considerable evidence exist for wide heterogeneity in the risk of CV events among T2DM patients and the concept of a "CAD risk equivalent" has changed. Recent guidelines recommend further CV risk stratification in T2DM patients, with treatment tailored to the risk level. Although imaging modalities for atherosclerotic cardiovascular disease (ASCVD) have been used to improve risk prediction, there is currently no evidence that imaging-oriented therapy improves clinical outcomes. Therefore, controversy remains whether we should screen for CVD in asymptomatic T2DM. The coexistence of T2DM and heart failure (HF) is common. Based on recent CV outcome trials, sodium glucose cotransporter-2 inhibitors and glucagon like peptide-1 receptor agonists are recommended who have established ASCVD, indicators of high risk, or HF because of their demonstrated benefits for CVD. These circumstances have led to an increasing emphasis on ASCVD and HF in T2DM patients. In this review, we examine the literature published within the last 5 years on the risk assessment of CVD in asymptomatic T2DM patients. In particular, we review recent guidelines regarding screening for CVD and research focusing on the role of coronary artery calcium, coronary computed tomography angiography, and carotid intima-media thickness in asymptomatic T2DM patients.
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Thrombotic risk in children undergoing orthopedic surgery.
Odent, T, de Courtivron, B, Gruel, Y
Orthopaedics & traumatology, surgery & research : OTSR. 2020;(1S):S109-S114
Abstract
Children are physiologically protected against venous thromboembolism (VTE). Specific triggering events or contributing factors have been identified in the majority of reported cases, which differs from the adult pathology where 50% of the thromboses are considered "idiopathic". This is a rare disease in children with an estimated frequency of less than 1/1000. The risk is highest in neonates, then decreases and increases again around 13 years to reach the same level as adults at 16 years. The risk of VTE is clearly higher in certain situations: significant trauma, prolonged immobilization, central venous catheter, stay in intensive care unit, inherited thrombophilia, cancer, obesity, oral contraceptives, etc. Thromboprophylaxis should not be used systematically, even in adolescents. Proper hydration and early mobilization form the basis of mechanical thromboprophylaxis. A prescription is only given after careful analysis of the child's risk factors and the orthopedic context. Thrombotic risk assessment scores - which are based on expert opinion and large VTE registers but have not been evaluated in clinical studies - are currently the most reliable method to evaluate the thrombotic risk in children and to prescribe thromboprophylaxis. Low-molecular weight heparin are the most commonly used thromboprophylaxis agents in children, with good tolerance and efficacy.
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Insulin Resistance in Obese Children: What Can Metabolomics and Adipokine Modelling Contribute?
Rupérez, FJ, Martos-Moreno, GÁ, Chamoso-Sánchez, D, Barbas, C, Argente, J
Nutrients. 2020;(11)
Abstract
The evolution of obesity and its resulting comorbidities differs depending upon the age of the subject. The dramatic rise in childhood obesity has resulted in specific needs in defining obesity-associated entities with this disease. Indeed, even the definition of obesity differs for pediatric patients from that employed in adults. Regardless of age, one of the earliest metabolic complications observed in obesity involves perturbations in glucose metabolism that can eventually lead to type 2 diabetes. In children, the incidence of type 2 diabetes is infrequent compared to that observed in adults, even with the same degree of obesity. In contrast, insulin resistance is reported to be frequently observed in children and adolescents with obesity. As this condition can be prerequisite to further metabolic complications, identification of biological markers as predictive risk factors would be of tremendous clinical utility. Analysis of obesity-induced modifications of the adipokine profile has been one classic approach in the identification of biomarkers. Recent studies emphasize the utility of metabolomics in the analysis of metabolic characteristics in children with obesity with or without insulin resistance. These studies have been performed with targeted or untargeted approaches, employing different methodologies. This review summarizes some of the advances in this field while emphasizing the importance of the different techniques employed.
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Incorporating Risk Stratification Into the Practice of Pediatric Preventive Cardiology.
Khoury, M, Kavey, RW, St Pierre, J, McCrindle, BW
The Canadian journal of cardiology. 2020;(9):1417-1428
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Abstract
Atherosclerosis in its earliest stages is associated with the same traditional cardiovascular disease (CVD) risk factors as are associated with manifest CVD events in adulthood. Clustering of risk factors is associated with exponential increases in atherosclerotic burden from a young age. Some medical conditions and risk behaviours occurring in children can either increase the likelihood of higher levels of risk factors (such as chronic kidney disease) or the presence of risk factor clustering (such as obesity and cardiometabolic syndrome) or are associated with acquired coronary artery pathology (such as Kawasaki disease). This creates a milieu for-or increases the impact of-accelerated atherosclerosis that, in turn, increases the likelihood of premature CVD. This review highlights the importance of considering the total risk factor and risk-condition profile of pediatric patients. An algorithm is provided for stratifying patients into high-, moderate-, and at-risk categories, and practical examples are provided as to how the evaluation and management of 1 risk factor or risk condition might need to be intensified in the context of additional risk factors or risk conditions. For example, for treatment of an adolescent with familial hypercholesterolemia, the target low-density lipoprotein cholesterol level might be lowered by the concomitant presence of low high-density lipoprotein cholesterol or elevated lipoprotein(a) levels. As awareness of cardiovascular risk and atherosclerosis in pediatric patients increases, new at-risk conditions that warrant consideration are emerging. The identification and management of high-risk individuals is an important part of the overall practice of pediatric preventive cardiology.
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Opportunities for improving use of evidence-based therapy in patients with type 2 diabetes and cardiovascular disease.
Gao, Y, Peterson, E, Pagidipati, N
Clinical cardiology. 2019;(11):1063-1070
Abstract
Evidence-based therapy that target hyperlipidemia, hypertension, smoking cessation, and weight loss have demonstrated significant benefits in reducing cardiovascular risks and related events. Although the benefit of intensively lowering blood glucose is unclear, newer antidiabetic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) have shown cardiovascular benefits in addition to their antihyperglycemic effect. Yet, studies suggest that recent use of evidence-based therapy and management of cardiovascular risk among individuals with type 2 diabetes (T2D) and cardiovascular disease (CVD) remains largely suboptimal. The following narrative review first identifies barriers to translating research evidence to clinical practice at the levels of provider, health system, patient, and cost. Then it synthesizes previous implementation strategies that addressed multifaceted barriers and attempted to improve care for patients with T2D and CVD. In conclusion, team-based care coordination, reminding systems in combination to pharmacist consultation and patient education, provider education compatible with clinical workflow, and coupled incentives between providers and patients appeared to be effective in reducing cardiovascular risks for patients with T2D and CVD, though the scalability and long-term clinical effect of these strategies as well as the possibility of interventions involving payers and health systems remain uncertain.
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Normal-weight central obesity: Unique hazard of the toxic waist.
Bosomworth, NJ
Canadian family physician Medecin de famille canadien. 2019;(6):399-408
Abstract
OBJECTIVE To examine the mortality risk presented by normal-weight central obesity, to identify a clinical measure to aid in the identification of this phenotype, and to explore the means for mitigation of this risk. QUALITY OF EVIDENCE Only prospective cohort studies (level II) comparing participants with central obesity at normal weight with those at higher levels of body mass index (BMI) were found. Good level I studies were available to demonstrate the effect of diet and exercise interventions on central obesity and mortality. MAIN MESSAGE Participants with atherogenic dyslipidemia who are centrally obese at normal BMI are at similar, and possibly higher, mortality risk compared with those who are centrally obese and overweight or obese according to their BMI. Waist-to-height ratio might be the most pragmatic clinical measure of central obesity. The Mediterranean diet is an effective intervention to prevent ongoing weight gain while reducing abdominal girth. Low levels of exercise can also reduce waist circumference. Weight loss need not be an objective. CONCLUSION A waist-to-height ratio exceeding 0.5 at normal BMI identifies elevated mortality risk for cardiometabolic disease. This risk might equal or exceed that of centrally obese patients who are overweight or obese. Modest dietary and exercise interventions can be effective in mitigation of this risk.
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The challenge of asymptomatic coronary artery disease in aircrew; detecting plaque before the accident.
Gray, G, Davenport, ED, Bron, D, Rienks, R, d'Arcy, J, Guettler, N, Manen, O, Syburra, T, Nicol, ED
Heart (British Cardiac Society). 2019;(Suppl 1):s17-s24
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Abstract
Coronary events remain a major cause of sudden incapacitation, including death, in both the general population and among aviation personnel, and are an ongoing threat to flight safety and operations. The presentation is often unheralded, especially in younger adults, and is often due to rupture of a previously non-obstructive coronary atheromatous plaque. The challenge for aeromedical practitioners is to identify individuals at increased risk for such events. This paper presents the NATO Cardiology Working Group (HFM 251) consensus approach for screening and investigation of aircrew for asymptomatic coronary disease.A three-phased approach to coronary artery disease (CAD) risk assessment is recommended, beginning with initial risk-stratification using a population-appropriate risk calculator and resting ECG. For aircrew identified as being at increased risk, enhanced screening is recommended by means of Coronary Artery Calcium Score alone or combined with a CT coronary angiography investigation. Additional screening may include exercise testing, and vascular ultrasound imaging. Aircrew identified as being at high risk based on enhanced screening require secondary investigations, which may include functional ischaemia, and potentially invasive coronary angiography. Functional stress testing as a stand-alone investigation for significant CAD is not recommended in aircrew. Aircrew identified with coronary disease require further clinical and aeromedical evaluation before being reconsidered for flying status.
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Risk Factor Variability and Cardiovascular Outcome: JACC Review Topic of the Week.
Messerli, FH, Hofstetter, L, Rimoldi, SF, Rexhaj, E, Bangalore, S
Journal of the American College of Cardiology. 2019;(20):2596-2603
Abstract
Until recently, intraindividual visit-to-visit variability of cardiovascular risk factors has been dismissed as random fluctuation. This simplistic concept was challenged by demonstrating that visit-to-visit blood pressure variability, independent of average blood pressure, was a powerful risk factor for stroke. Subsequently, variability of other cardiovascular risk factors such as cholesterol, glycemia, and body weight was documented to increase risk independent of their absolute values. Variability of these risk factors has been demonstrated to be a powerful predictor for all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia. With the notable exception of heart rate, cardiovascular risk factors must now be defined by 2 components: the magnitude and duration of sustained risk factor elevation and, equally important, the variability of the same risk factor over time.