Risk Factor Characterization of Ischemic Stroke Subtypes Among West Africans.

BACKGROUND AND PURPOSE: To identify the qualitative and quantitative contributions of conventional risk factors for occurrence of ischemic stroke and its key pathophysiologic subtypes among West Africans. METHODS: The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with ischemic stroke who were etiologically subtyped using the A-S-C-O-D classification into atherosclerosis, small-vessel occlusion, cardiac pathology, other causes, and dissection. Controls were age- and gender-matched stroke-free adults. Detailed evaluations for vascular, lifestyle, and psychosocial factors were performed. We used conditional logistic regression to estimate adjusted odds ratios with 95% CI. RESULTS: There were 2431 ischemic stroke case and stroke-free control pairs with respective mean ages of 62.2±14.0 versus 60.9±13.7 years. There were 1024 (42.1%) small vessel occlusions, 427 (17.6%) large-artery atherosclerosis, 258 (10.6%) cardio-embolic, 3 (0.1%) carotid dissections, and 719 (29.6%) undetermined/other causes. The adjusted odds ratio (95% CI) for the 8 dominant risk factors for ischemic stroke were hypertension, 10.34 (6.91-15.45); dyslipidemia, 5.16 (3.78-7.03); diabetes, 3.44 (2.60-4.56); low green vegetable consumption, 1.89 (1.45-2.46); red meat consumption, 1.89 (1.45-2.46); cardiac disease, 1.88 (1.22-2.90); monthly income $100 or more, 1.72 (1.24-2.39); and psychosocial stress, 1.62 (1.18-2.21). Hypertension, dyslipidemia, diabetes were confluent factors shared by small-vessel, large-vessel and cardio-embolic subtypes. Stroke cases and stroke-free controls had a mean of 5.3±1.5 versus 3.2±1.0 adverse cardio-metabolic risk factors respectively (P<0.0001). CONCLUSIONS: Traditional vascular risk factors demonstrate important differential effect sizes with pathophysiologic, clinical and preventative implications on the occurrence of ischemic stroke among indigenous West Africans.

A novel model of myocardial infarction based on atherosclerosis in mice.

RATIONALE: Coronary artery ligation to induce myocardial infarction (MI) and ischemia injury in mice is typically performed in normal mice, but This is not consistent with disease progression. There should be atherosclerosis (AS) first, followed by MI. OBJECTIVE: We tried a novel model to induce MI that was established on atherosclerosis in mice. This approach was much more consistent with disease progression. METHODS: In this study, Mice lacking apolipoprotein E (ApoE-/-) were randomly divided into four groups. The mice of the control and MI groups were fed normal diet for 24-weeks, while the mice of AS and AS + MI groups were fed high-fat diet (HFD). After 23 weeks, the mice of MI and AS + MI groups were ligated with coronary arteries. A week later, after echocardiography, analysis of plaque and myocardium were conducted on aortic and heart, then the serum, aorta and heart tissues were further detected. RESULTS: Our results showed that AS model mice exhibited significant body weight gain, dyslipidemia and atherosclerotic lesions formation which were in accordance with the pathological changes of AS. Co-treatment with AS and MI led to higher operative mortality and heart pathological were in accordance with the pathological changes of MI. In addition, Echocardiography and NT pro-BNP revealed co-treatment with AS and MI led to deterioration of cardiac function. AS also aggravated myocardial inflammatory cell infiltration and fibrosis post-MI. CONCLUSIONS: Together, it is feasible to establish myocardial infarction model based on atherosclerosis model.

Cardiovascular risk management in type 2 diabetes mellitus: A joint position paper of the Italian Cardiology (SIC) and Italian Diabetes (SID) Societies.

AIM: This review represents a joint effort of the Italian Societies of Cardiology (SIC) and Diabetes (SID) to define the state of the art in a field of great clinical and scientific interest which is experiencing a moment of major cultural advancements, the cardiovascular risk management in type 2 diabetes mellitus. DATA SYNTHESIS: Consists of six chapters that examine various aspects of pathophysiology, diagnosis and therapy which in recent months have seen numerous scientific innovations and several clinical studies that require extensive sharing. CONCLUSIONS: The continuous evolution of our knowledge in this field confirms the great cultural vitality of these two cultural spheres, which requires, under the leadership of the scientific Societies, an ever greater and effective collaboration.

Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation.

Dyslipidemia is commonly linked to skeletal muscle dysfunction, accumulation of intramyocellular lipids, and insulin resistance. However, our previous research indicated that dyslipidemia in apolipoprotein E and low-density lipoprotein receptor double knock-out mice (ApoE/LDLR -/-) leads to improvement of exercise capacity. This study aimed to investigate in detail skeletal muscle function and metabolism in these dyslipidemic mice. We found that ApoE/LDLR -/- mice showed an increased grip strength as well as increased troponins, and Mhc2 levels in skeletal muscle. It was accompanied by the increased skeletal muscle mitochondria numbers (judged by increased citrate synthase activity) and elevated total adenine nucleotides pool. We noted increased triglycerides contents in skeletal muscles and increased serum free fatty acids (FFA) levels in ApoE/LDLR -/- mice. Importantly, Ranolazine mediated inhibition of FFA oxidation in ApoE/LDLR -/- mice led to the reduction of exercise capacity and total adenine nucleotides pool. Thus, this study demonstrated that increased capacity for fatty acid oxidation, an adaptive response to dyslipidemia leads to improved cellular energetics that translates to increased skeletal muscle strength and contributes to increased exercise capacity in ApoE/LDLR -/- mice.

Increasing the Power of Polyphenols through Nanoencapsulation for Adjuvant Therapy against Cardiovascular Diseases.

Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.

Clinical approach to the inflammatory etiology of cardiovascular diseases.

Inflammation is an obligatory marker of arterial disease, both stemming from the inflammatory activity of cholesterol itself and from well-established molecular mechanisms. Raised progenitor cell recruitment after major events and clonal hematopoiesis related mechanisms have provided an improved understanding of factors regulating inflammatory phenomena. Trials with inflammation antagonists have led to an extensive evaluation of biomarkers such as the high sensitivity C reactive protein (hsCRP), not exerting a causative role, but frequently indicative of the individual cardiovascular (CV) risk. Aim of this review is to provide indication on the anti-inflammatory profile of agents of general use in CV prevention, i.e. affecting lipids, blood pressure, diabetes as well nutraceuticals such as n-3 fatty acids. A crucial issue in the evaluation of the benefit of the anti-inflammatory activity is the frequent discordance between a beneficial activity on a major risk factor and associated changes of hsCRP, as in the case of statins vs PCSK9 antagonists. In hypertension, angiotensin converting enzyme inhibitors exert an optimal anti-inflammatory activity, vs the case of sartans. The remarkable preventive activity of SLGT-2 inhibitors in heart failure is not associated with a clear anti-inflammatory mechanism. Finally, icosapent ethyl has been shown to reduce the CV risk in hypertriglyceridemia, with a 27 % reduction of hsCRP. The inflammation-based approach to arterial disease has considerably gained from an improved understanding of the clinical diagnostic strategy and from a better knowledge on the mode of action of numerous agents, including nutraceuticals.

Dyslipidemia and cardiovascular health in childhood nephrotic syndrome.

Children with steroid-resistant nephrotic syndrome (SRNS) are exposed to multiple cardiovascular risk factors predisposing them to accelerated atherosclerosis. This risk is negligible in steroid-sensitive nephrotic syndrome, but a substantial proportion of children with SRNS progress to chronic kidney disease, exacerbating the already existing cardiovascular risk. While dyslipidemia is an established modifiable risk factor for cardiovascular disease in adults with NS, it is uncertain to what extent analogous risks exist for children. There is increasing evidence of accelerated atherosclerosis in children with persistently high lipid levels, especially in refractory NS. Abnormalities of lipid metabolism in NS include hypertriglyceridemia and hypercholesterolemia due to elevated apolipoprotein B-containing lipoproteins, decreased lipoprotein lipase and hepatic lipase activity, increased hepatic PCSK9 levels, and reduced hepatic uptake of high-density lipoprotein. Existing guidelines for the management of dyslipidemia in children may be adapted to target lower lipid levels in children with NS, but they will most likely require both lifestyle modifications and pharmacological therapy. While there is a lack of data from randomized controlled trials in children with NS demonstrating the benefit of lipid-lowering drugs, therapies including statins, bile acid sequestrants, fibrates, ezetimibe, and LDL apheresis have all been suggested and/or utilized. However, concerns with the use of lipid-lowering drugs in children include unclear side effect profiles and unknown long-term impacts on neurological development and puberty. The recent introduction of anti-PCSK9 monoclonal antibodies and other therapies targeted to the molecular mechanisms of lipid transport disrupted in NS holds promise for the future treatment of dyslipidemia in NS.

Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity.

BACKGROUND AND AIM: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis. METHODS AND RESULTS: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect ß = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. CONCLUSION: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.

Short- and long-term effects of maternal dyslipidaemia on blood pressure and baroreflex sensitivity in male rat offspring.

Maternal dyslipidaemia is a predisposing factor for arterial hypertension in male rat offspring at adulthood. This study was designed to investigate the short- and long-term effects of maternal dyslipidaemia on blood pressure (BP) and baroreflex control in male rat offspring. Animals were obtained from mothers who received a dyslipidaemic (DLP, n = 7) or control (CTL, n = 7) diet during pregnancy and lactation. At 30 and 90 days of age, arterial pressure (AP), heart rate (HR) and baroreflex function were evaluated. In addition, spectral analysis of the systolic AP, diastolic AP, mean AP, HR, and spontaneous baroreflex were assessed. Data were expressed as mean ± SEM and Student's t-test was used for comparison among groups, with statistical significance considered to be P < .05. At 30 days of age, male offspring had similar BP, HR and preserved baroreflex sensitivity. In addition, low frequency (LF) oscillation, high frequency (HF) oscillation and LF/HF ratio of AP and HR were similar in juvenile rats. At 90 days of age, male offspring from dyslipidaemic dams had augmented BP (P < .05) when compared to CTL group. Adult male rats from dyslipidaemic dams had a reduction in baroreflex control (P < .05) in comparison to CTL rats. The present study indicates that offspring from dams fed on a dyslipidaemic diet during pregnancy and lactation do not show alteration in blood pressure and baroreflex control in early life, but display a decline in baroreflex control and hypertension in adulthood.

Lipid disorders in children living with overweight and obesity- large cohort study from Poland.

BACKGROUND: While in the general paediatric population the presence of abnormal lipid values is estimated at 8-20%, depending on the population, accepted norms and age, it was shown that in the population of lean children the prevalence of dyslipidemia is lower than in obese children, in whom it ranges from 20 to over 40%. Until now, however, no results of similar studies on a large sample of children form a Central or Eastern European country have been published. The aim of this study was to evaluate the prevalence of lipid disorders in overweight and obese children and adolescents participating in an integrated weight reduction programme. METHODS: According to the "6-10-14 for Health" programme implementation schedule, the programme accepted patients living in Gdansk, aged 6, 9-11 and 14 years old, with BMI above the 85th percentile for age and sex, according to the Polish percentile charts. During the first visit, each of the participants underwent basic anthropometric examinations - body weight, body height, waist and hip circumference, blood pressure and body composition by bioelectrical impedance were measured. Blood samples were taken to assess lipid, glucose and insulin levels as well as alanine transaminase (ALT) and thyroid stimulating hormone (TSH) activity. RESULTS: 1948 patients underwent full anthropomethric and blood work measurements. At least one of the lipid disorders occurred in 38.23% of girls and 40.51% of boys with overweight and obesity. The most common lipid disorderswere decreased high-density lipoprotein cholesterol (HDL-C) levels (present in 20.55% of the girls and 23.79% of the boys) and elevated low-density lipoprotein cholesterol (LDL-C) (present in 15.31% of the girls and 14.25% of the boys). There was no strong association between lipid disorders and age, sex, birth weight, gestational age at birth or body composition. CONCLUSIONS: Such a frequent occurrence of lipid disorders in the population of children and adolescents should be an important warning signal both at the individual and population level. Not only effective screening methods for overweight and obese children should be implemented from an early age but also therapeutic measures are required. TRIAL REGISTRATION: The trial is registered under the Local Ethics Committee at Medical University of Gdansk, decision No. NKBBN/228/2012 from 25 June 2012.

The Association between Inflammation and Pulse Wave Velocity in Dyslipidemia: An Evidence-Based Review.

Dyslipidemia is associated with increased arterial stiffness (AS) which may lead to hypertension. Among the methods to assess AS are carotid-femoral and brachial-ankle pulse wave velocity. Dyslipidemia is also known to trigger inflammation. C-reactive protein (CRP) is one of the commonest inflammatory markers measured in the clinical setting. However, the association between inflammation and pulse wave velocity (PWV) in people with dyslipidemia is less studied. Therefore, this review investigated the association between inflammation (as measured by CRP) and PWV in dyslipidemia patients. The search of the literature was conducted via PubMed and Scopus database. The keywords used were "aortic stiffness" OR "arterial stiffness" OR "pulse wave velocity" OR "vascular stiffness" OR "carotid femoral pulse wave velocity" OR "pulse wave analysis" AND "inflammation" OR "c reactive protein" OR "c-reactive protein" OR "high sensitivity c reactive protein" AND "dyslipidemia" OR "hyperlipidemia" OR "hypercholesterolemia" OR "hyperlipoproteinemia" OR "hypertriglyceridemia". The following criteria were used: (1) only full-length original articles published in English language, (2) articles that reported the association between arterial stiffness measured as carotid-femoral PWV (cfPWV) or brachial-ankle PWV (baPWV) and CRP or high-sensitivity CRP, and (3) study involving human subjects. The search identified 957 articles published between 1980 and February 2020. Only eight articles fulfilled the inclusion criteria and were used for data extraction. Five of the studies were cross-sectional studies while another three studies were interventional studies. Seven out of eight papers found a significant positive association between AS and CRP, and the correlation ranged from mild to moderate association (Pearson r = 0.33 to r = 0.624). In conclusion, inflammation is associated with increased PWV in patients with dyslipidemia. This supports the involvement of inflammation in the development of AS in dyslipidemia.

Mechanisms linking preterm birth to onset of cardiovascular disease later in adulthood.

Cardiovascular disease (CVD) rates in adulthood are high in premature infants; unfortunately, the underlying mechanisms are not well defined. In this review, we discuss potential pathways that could lead to CVD in premature babies. Studies show intense oxidant stress and inflammation at tissue levels in these neonates. Alterations in lipid profile, foetal epigenomics, and gut microbiota in these infants may also underlie the development of CVD. Recently, probiotic bacteria, such as the mucin-degrading bacterium Akkermansia muciniphila have been shown to reduce inflammation and prevent heart disease in animal models. All this information might enable scientists and clinicians to target pathways to act early to curtail the adverse effects of prematurity on the cardiovascular system. This could lead to primary and secondary prevention of CVD and improve survival among preterm neonates later in adult life.

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease.

Chronic kidney disease (CKD) is a worldwide health problem with steadily increasing occurrence. Significantly elevated cardiovascular morbidity and mortality have been observed in CKD. Cardiovascular diseases are the most important and frequent cause of death of CKD patients globally. The presence of CKD is related to disturbances in lipoprotein metabolism whose consequences are dyslipidemia and the accumulation of atherogenic particles. CKD not only fuels the reduction of high-density lipoprotein (HDL) cholesterol concentration, but also it modifies the composition of this lipoprotein. The key role of HDL is the participation in reverse cholesterol transport from peripheral tissues to the liver. Moreover, HDL prevents the oxidation of low-density lipoprotein (LDL) cholesterol by reactive oxygen species (ROS) and protects against the adverse effects of oxidized LDL (ox-LDL) on the endothelium. Numerous studies have demonstrated the ability of HDL to promote the production of nitric oxide (NO) by endothelial cells (ECs) and to exert antiapoptotic and anti-inflammatory effects. Increasing evidence suggests that in patients with chronic inflammatory disorders, HDLs may lose important antiatherosclerotic properties and become dysfunctional. So far, no therapeutic strategy to raise HDL, or alter the ratio of HDL subfractions, has been successful in slowing the progression of CKD or reducing cardiovascular disease in patients either with or without CKD.

Effects of Extracardiac Factors in Signal-Averaged Electrocardiography-measured Late Potentials from Early Anterior Myocardial Infarction in Intensive Cardiac Care Unit.

BACKGROUND: one modality that can predict ventricular arrhythmias after myocardial infarction (MI), particularly anterior MI, is signal-averaged electrocardiogram (SA-ECG), through the detection of late potentials (LP) which is a substrate for ventricular arrhythmias. Extracardiac factors, which are also risk factors for MI, such as hypertension, diabetes, dyslipidemia, and obesity, are apparently associated with post-MI ventricular arrhythmias, which in turn may be correlated with LP. This study aims to determine the effect of extracardiac risk factors on LP incidence in anterior MI patients treated in the intensive cardiac care unit (ICCU). METHODS: this was a cross-sectional study in which 80 subjects with anterior MI during the period of December 2018-2019 underwent SA-ECG examination. The medical history and extracardiac risk factors were recapitulated, and then the SA-ECG data was taken from either direct examination or ICCU patients' database in that period. This study used multivariate analysis with logistic regression test. RESULTS: the most common factors found were hypertension (70.00%), followed by dyslipidemia (56.25%), diabetes (46.25%), and obesity (38.75%). Obesity and dyslipidemia are extracardiac factors with the two biggest roles in the prevalence of LP. However, from additional analysis, we found that diabetes with acute hyperglycemia also had immense influence on the occurrence of LP. The OR for diabetes with acute hyperglycemia, obesity, and dyslipidemia were 4.806 (IK95% 0.522-44.232), 4.291 (IK95% 0.469-39.299), and 3.237 (IK95% 0.560-18.707). However, the association is not statistically significant. CONCLUSION: patients with anterior MI who suffer from diabetes with hyperglycemia in admission, obesity, and dyslipidemia have a potentially higher LP prevalence, despite statistical insignificance. To increase the prognostic value of SA-ECG, serial examinations are needed during hospitalization.

Patterns of ascending aortic dilatation and predictors of surgical replacement of the aorta: A comparison of bicuspid and tricuspid aortic valve patients over eight years of follow-up.

BACKGROUND: Predictors of thoracic aorta growth and early cardiac surgery in patients with bicuspid aortic valve are undefined. Our aim was to identify predictors of ascending aorta dilatation and cardiac surgery in patients with bicuspid aortic valve (BAV). METHODS: Forty-one patients with BAV were compared with 165 patients with tricuspid aortic valve (TAV). All patients had LV EF > 50%, normal LV dimensions, and similar degree of aortic root or ascending aorta dilatation at enrollment. Patients with more than mild aortic stenosis or regurgitation were excluded. A CT-scan was available on 76% of the population, and an echocardiogram was repeated every year for a median time of 4 years (range: 2 to 8 years). Patterns of aortic expansion in BAV and TAV groups were analyzed by a mixed-effects longitudinal linear model. In the time-to-event analysis, the primary end point was elective or emergent surgery for aorta replacement. RESULTS: BAV patients were younger, while the TAV group had greater LV wall thickness, arterial hypertension, and dyslipidemia than BAV patients. Growth rate was 0.46 ±â€¯0.04 mm/year, similar in BAV and TAV groups (p = 0.70). Predictors of cardiac surgery were aorta dimensions at baseline (HR 1.23, p = 0.01), severe aortic regurgitation developed during follow-up (HR 3.49, p 0.04), family history of aortic aneurysm (HR 4.16, p 1.73), and history of STEMI (HR 3.64, p < 0.001). CONCLUSIONS: Classic baseline risk factors were more commonly observed in TAV aortopathy compared with BAV aortopathy. However, it is reassuring that, though diagnosed with aneurysm on average 10 years earlier and in the absence of arterial hypertension, BAV patients had a relatively low growth rate, similar to patients with a tricuspid valve. Irrespective of aortic valve morphology, patients with a family history of aortic aneurysm, history of coronary artery disease, and those who developed severe aortic regurgitation at follow-up, had the highest chances of being referred for surgery.

Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial.

BACKGROUND: We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. METHODS: We performed an 18-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to isocaloric low-fat or Mediterranean/low-carbohydrate (MED/LC) diet+28 g walnuts/day with/without added moderate physical activity (PA; 80% aerobic; supervised/free gym membership). Overall primary outcome was body fat redistribution, and the main specific end point was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots (deep and superficial subcutaneous, liver, pericardial, muscle, pancreas, and renal sinus) by magnetic resonance imaging. RESULTS: Of 278 participants (age, 48 years, 89% men, body mass index, 30.8 kg/m2), 86% completed the trial with good adherence. The low-fat group preferentially decreased reported fat intake (-21.0% versus -11.5% for the MED/LC; P<0.001), and the MED/LC group decreased reported carbohydrates intake (-39.5% versus -21.3% for the low-fat group; P<0.001). The PA+ groups significantly increased the metabolic equivalents per week versus the PA- groups (19.0 versus 2.1; P=0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in the MED/LCPA+ group (P<0.05). VAT (-22%), intrahepatic (-29%), and intrapericardial (-11%) fats declines were higher than pancreatic and femur intermuscular fats (1% to 2%) loss. Independent of weight loss, PA+ with either diet had a significantly greater effect on decreasing VAT (mean of difference, -6.67cm2; 95% confidence interval, -14.8 to -0.45) compared with PA-. The MED/LC diet was superior to the low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fats (P<0.05 for all). In contrast, renal sinus and femoral intermuscular fats were not differentially altered by lifestyle interventions but by weight loss per se. In multivariate models further adjusted for weight loss, losing VAT or intrahepatic fat was independently associated with improved lipid profile, losing deep subcutaneous adipose tissue with improved insulin sensitivity, and losing superficial subcutaneous adipose tissue remained neutral except for an association with decreased leptin. CONCLUSIONS: Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomic sites. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01530724.

Intermittent normobaric hypoxia facilitates high altitude acclimatization by curtailing hypoxia-induced inflammation and dyslipidemia.

Intermittent hypoxic training (IHT) is a discrete cost-effective method for improving athletic performance and high altitude acclimatization. Unfortunately, IHT protocols widely vary in terms of hypoxia severity, duration, and number of cycles affecting physiological outcomes. In the present study, we evaluated the efficacy of a moderate normobaric IHT protocol (12% FiO2 for 4 h, 4 days) on acclimatization to high altitude (3250 m). Global plasma proteomics studies revealed that IHT elicited acute-phase response proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and alpha-1-acid glycoprotein 2 (AGP 2) as well as altered levels of several apolipoproteins. On subsequent exposure to high altitude, the IH trained volunteers exhibited significant higher arterial oxygen saturation with concomitant lower incidences of acute mountain sickness (AMS) as compared to controls. Interestingly, IH trained subjects exhibited lower levels of positive acute-phase proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and fibrinogen (FGA, FGB, and FGG) both after days 4 and 7 of high altitude ascent. High altitude exposure also decreased the levels of HDL, LDL, and associated proteins as well as key enzymes for assembly and maturation of lipoprotein particles like lecithin-cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). In contrast, IHT curtailed hypoxia-induced alterations of HDL, LDL, Apo-AI, Apo-B, LCAT, CETP, and PLTP. Further validation of results also corroborated attenuation of hypoxia-induced inflammation and dyslipidemia by IHT. These results provide molecular evidences supporting the use of moderate IHT as a potential non-pharmacological strategy for high altitude acclimatization.

Severe obesity and cardio-metabolic comorbidities: a nationwide study of 2.8 million adolescents.

BACKGROUND: Severe obesity is rising among adolescents, but data on the prevalence of metabolic abnormalities among this group are limited. We assessed the secular trend of severe obesity and its association with major cardio-metabolic morbidities. METHODS: A total of 2,785,227 Israeli adolescents (aged 17.2 ± 0.5 years) who underwent a pre-recruitment medical examination including routine measurements of weight, height and blood pressure between 1967 and 2015 were included. In all, 230,639 adolescents with abnormally excessive BMI were classified into overweight, classes I, II, and III (severe) obesity. Logistic regression was applied to determine the association between BMI groups and prehypertension, high blood pressure and type 2 diabetes (T2DM). RESULTS: There was 45-fold increase in the prevalence of class III obesity during study period. Severe obesity was recorded in 2060 males and 1149 females, in whom nearly 35 and 43% had prehypertension or high blood pressure, respectively. Compared with adolescents with overweight, the odds ratios (ORs) for high blood pressure in classes II and III obesity groups, respectively, were 2.13 (95% CI, 2.04-2.23) and 2.86 (2.60-3.15) in males, and 2.59 (2.43-2.76) and 3.44 (3.04-3.90) in females, whereas the ORs for T2DM were 19.1 (12.3-29.6) and 38.0 (22.6-64.0) in males, and 15.1 (11.4-20.0) and 24.8 (17.2-35.7) in females. Results persisted in extensive sensitivity analyses including a longitudinal follow-up (median: males, 3.4 years; females, 4.9 years). CONCLUSIONS: Severe obesity showed a marked secular increase and was associated with significantly higher risk for abnormal blood pressure and T2DM than lower degrees of obesity, in both males and females.

Effects of 1 year of exercise training versus combined exercise training and weight loss on body composition, low-grade inflammation and lipids in overweight patients with coronary artery disease: a randomized trial.

BACKGROUND: Dyslipidaemia and low-grade inflammation are central in atherogenesis and linked to overweight and physical inactivity. Lifestyle changes are important in secondary prevention of coronary artery disease (CAD). We compared the effects of combined weight loss and interval training with interval training alone on physical fitness, body composition, dyslipidaemia and low-grade inflammation in overweight, sedentary participants with CAD. METHODS: Seventy CAD patients, BMI 28-40 kg/m2 and age 45-75 years were randomised to (1) 12 weeks' aerobic interval training (AIT) at 90% of peak heart rate three times/week followed by 40 weeks' AIT twice weekly or (2) a low energy diet (LED) (800-1000 kcal/day) for 8-10 weeks followed by 40 weeks' weight maintenance including AIT twice weekly and a high-protein/low-glycaemic load diet. Effects of the intervention were evaluated by physical fitness, body weight and composition. Dyslipidaemia was described using both biochemical analysis of lipid concentrations and lipoprotein particle subclass distribution determined by density profiling. Low-grade inflammation was determined by C-reactive protein, soluble urokinase-type plasminogen activator receptor and tumour necrosis factor α. Effects on continuous outcomes were tested by mixed-models analysis. RESULTS: Twenty-six (74%) AIT and 29 (83%) LED + AIT participants completed the study. At baseline subject included 43 (78%) men; subjects averages were: age 63 years (6.2), body weight 95.9 kg (12.2) and VO2peak 20.7 mL O2/kg/min (4.9). Forty-six (84%) had pre-diabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). LED + AIT reduced body weight by 7.2 kg (- 8.4; - 6.1) and waist circumference by 6.6 cm (- 7.7; - 5.5) compared to 1.7 kg (- 0.7; - 2.6) and 3.3 cm (- 5.1; - 1.5) after AIT (within-group p < 0.001, between-group p < 0.001 and p = 0.018, respectively). Treatments caused similar changes in VO2peak and lowering of total cholesterol, triglycerides, non-HDL cholesterol and low-grade inflammation. A shift toward larger HDL particles was seen following LED + AIT while AIT elicited no change. CONCLUSIONS: Both interventions were feasible. Both groups obtained improvements in VO2peak, serum-lipids and inflammation with superior weight loss and greater central fat loss following LED + AIT. Combined LED induced weight loss and exercise can be recommended to CAD patients. Trial registration NCT01724567, November 12, 2012, retrospectively registered (enrolment ended in April 2013).

Cardiovascular disease management in people with diabetes outside North America and Western Europe in 2006 and 2015.

AIM: Optimal treatment of cardiovascular disease is essential to decrease mortality among people with diabetes, but information is limited on how actual treatment relates to guidelines. We analysed changes in therapeutic approaches to anti-hypertensive and lipid-lowering medications in people with Type 2 diabetes from 2006 and 2015. METHODS: Summary data from clinical services in seven countries outside North America and Western Europe were collected for 39 684 people. Each site summarized individual-level data from outpatient medical records for 2006 and 2015. Data included: demographic information, blood pressure (BP), total cholesterol levels and percentage of people taking statins, anti-hypertensive medication (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor blockers, thiazide diuretics) and antiplatelet drugs. RESULTS: From 2006 to 2015, mean cholesterol levels decreased in six of eight sites (range: -0.5 to -0.2), whereas the proportion with BP levels > 140/90 mmHg increased in seven of eight sites. Decreases in cholesterol paralleled increases in statin use (range: 3.1 to 47.0 percentage points). Overall, utilization of anti-hypertensive medication did not change. However, there was an increase in the use of angiotensin II receptor blockers and a decrease in angiotensin-converting enzyme inhibitors. The percentage of individuals receiving calcium channel blockers and aspirin remained unchanged. CONCLUSIONS: Our findings indicate that control of cholesterol levels improved and coincided with increased use of statins. The percentage of people with BP > 140/90 mmHg was higher in 2015 than in 2006. Hypertension treatment shifted from using angiotensin-converting enzyme inhibitors to angiotensin II receptor blockers. Despite the potentially greater tolerability of angiotensin II receptor blockers, there was no associated improvement in BP levels.