[DIAGNOSIS AND TREATMENT OF ELEVATED LIPOPROTEIN(A) IN ISRAEL: CONSENSUS STATEMENT FROM THE ISRAEL SOCIETY FOR RESEARCH, PREVENTION AND TREATMENT OF ATHEROSCLEROSIS AND ISRAEL SOCIETY FOR CLINICAL LABORATORY SCIENCES].

INTRODUCTION: Lipoprotein(a) [Lp(a)] is composed of 2 major protein components, a low-density lipoprotein (LDL) cholesterol-like particle containing apolipoprotein B (apo B) that is covalently bound to apolipoprotein(a). Its level is predominantly genetically determined, and it is estimated that 20% to 25% of the population have Lp(a) levels that are associated with increased cardiovascular risk. Elevated Lp(a) is related to increased vascular inflammation, calcification, atherogenesis and thrombosis, and is considered an independent and potentially causal risk factor for atherosclerotic cardiovascular diseases and calcified aortic valve stenosis. Recent data demonstrate that Lp(a) testing has the potential to reclassify patients' risk and improve cardiovascular risk prediction, and therefore could inform clinical decision-making regarding risk management. Statins and ezetimibe are ineffective in lowering Lp(a) levels, whereas proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have a modest effect on Lp(a) reduction. Nevertheless, RNA interference-based therapies with potent Lp(a)-lowering effects are in advanced stages of development, and clinical trials are underway to confirm their benefit in reducing cardiovascular events. This scientific consensus document was developed by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, and the Israeli Society for Clinical Laboratory Sciences, in order to create uniformity in Lp(a) measurement methods, indications for testing and reporting of the results, aiming to improve the diagnosis and management of elevated Lp(a) in clinical practice.

Downstream Imaging Studies Do Not Significantly Improve Outcome in Most Patients with Chest Pain Who Did Not Reach Their Target Heart Rate on a Stress ECHO Study.

Echocardiographic stress tests are often used to evaluate patients who complain of chest pain. However, some patients fail to reach the target heart rate required for the test to be conclusive (usually defined as 85% of the predicted maximal heart rate based on the patient's age) and are often sent for additional imaging tests, such as myocardial perfusion imaging (MPI) or cardiac computed tomography angiography (CTA). Few studies have evaluated the effectiveness of these additional tests in patients who present with chest pain but did not meet the heart rate requirements for a stress test. The primary objective of the study was to evaluate the efficacy of additional imaging tests for patients who experience chest pain during daily activities but are unable to reach the target heart rate currently required for an echocardiographic stress test. The study group included 415 consecutive patients who underwent a stress echocardiogram, did not achieve their target heart rate, and did not demonstrate abnormal changes during the test. The control group consisted of 415 consecutive patients who did reach their target heart rate and demonstrated no signs of ischemia. Demographic and clinical data, medication use, imaging test results (MPI, CTA, and/or coronary catheterization) and documented cardiac events that occurred during 1 year of follow-up were obtained from the electronic medical records. Of the 415 patients in the study group, 73 (17.6%) were referred to another imaging test within 12 months. Of these 73 patients, 59 underwent MPI and 14 underwent cardiac CTA. In 12 of these patients (16.4%) the test was considered to be abnormal, but only 7 patients (1.7%) subsequently underwent a percutaneous intervention (PCI). In the control group, 28 (6.7%) patients were referred for another imaging test. Of these 28 patients, 14 underwent MPI and 14 underwent cardiac CTA. None of these tests were found to be abnormal, but two patients (0.5%) underwent a PCI (p = 0.2 between groups). There were no deaths during the study period and no patients underwent bypass surgery. The majority of the patients who underwent PCI had additional clinical risk factors (diabetes, hypertension, and/or known coronary artery disease), had taken a beta blocker within 24 h prior to the test, and/or did not reach a heart rate above 78% of their target heart rate. Our study suggests that in most patients with chest pain who do not show ischemic changes on a stress echocardiogram, additional imaging studies can be safely deferred, even if the required target heart rate was not reached. However, in patients with diabetes and/or known coronary disease, those who took a beta blocker 24 h prior to the test, or those who did not achieve a heart rate above 78% of the current target heart rate, additional imaging studies should be considered.

Detection of Common Arrhythmias by the Watch-PAT: Expression of Electrical Arrhythmias by Pulse Recording.

Background: The WatchPAT (WP) device was shown to be accurate for the diagnosis of sleep apnea and is widely used worldwide as an ambulatory diagnostic tool. While it records peripheral arterial tone (PAT) and not electrocardiogram (ECG), the ability of it to detect arrhythmias is unknown and was not studied previously. Common arrhythmias such as atrial fibrillation (AF) or premature beats may be uniquely presented while recording PAT/pulse wave. Purpose: To examine the potential detection of common arrhythmias by analyzing the PAT amplitude and pulse rate/volume changes. Patients and Methods: Patients with suspected sleep disordered breathing (SDB) were recruited with preference for patients with previously diagnosed AF or congestive heart failure (CHF). They underwent simultaneous WP and PSG studies in 11 sleep centers. A novel algorithm was developed to detect arrhythmias while measuring PAT and was tested on these patients. Manual scoring of ECG channel (recorded as part of the PSG) was blinded to the automatically analyzed WP data. Results: A total of 84 patients aged 57±16 (54 males) participated in this study. Their BMI was 30±5.7Kg/m2. Of them, 41 had heart failure (49%) and 17 (20%) had AF. The sensitivity and specificity of the WP to detect AF segments (of at least 60 seconds) were 0.77 and 0.99, respectively. The correlation between the WP derived detection of premature beats (events/min) to that of the PSG one was 0.98 (p<0.001). Conclusion: The novel automatic algorithm of the WP can reasonably detect AF and premature beats. We suggest that when the algorithm raises a flag for arrhythmia, the patients should shortly undergo ECG and/or Holter ECG study.

[UPDATED ISRAELI GUIDELINES FOR THE TREATMENT OF DYSLIPIDEMIA 2020].

INTRODUCTION: Despite the impressive decline in mortality from atherosclerotic cardiovascular diseases (ASCVD), these diseases still account for a large proportion of the overall morbidity and mortality worldwide. A vast amount of research has demonstrated the key role played by circulating lipoproteins, and especially low-density lipoprotein (LDL), in the etiology of atherosclerosis, and numerous studies have proven the efficacy of interventions that lower the atherogenic lipoproteins in reducing morbidity and mortality from ASCVD. While previous guidelines placed an emphasis on the use HMG-CoA reductase inhibitors (statins) for the treatment of dyslipidemia, recent studies have shown that other LDL cholesterol lowering drugs, including ezetimibe and the PCSK9 inhibitors, can provide additional benefit when used in combination with (and in certain cases instead of) statins. These studies have also shown that blood LDL cholesterol levels lower than previously recommended targets provide additional benefit, without evidence of a threshold beyond which the benefit ceases and without excess adverse effects. The updated guidelines were formulated by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, the Israel Society of Internal Medicine, the Israeli Heart Association, the Israeli Neurology Association and the Israel Association of Family Medicine. They provide recommendations for revised risk stratification of patients, novel target goals, and the use of evidence-based treatment and follow-up strategies with reference to specific patient sub-groups.

Effect of wine on carotid atherosclerosis in type 2 diabetes: a 2-year randomized controlled trial.

BACKGROUND/OBJECTIVES: The progression of carotid-plaque volume in patients with type 2 diabetes is common. Previous observational studies showed an association between moderate alcohol and reduced risk of coronary disease. We examined whether consuming moderate wine affects the progression of carotid atherosclerosis. SUBJECTS/METHODS: In the CASCADE (CArdiovaSCulAr Diabetes and Ethanol), a 2-year randomized controlled trial, we randomized abstainers with type 2 diabetes were to drink 150 ml of either red wine, white wine, or water, provided for 2 years. In addition, groups were guided to maintain a Mediterranean diet. We followed 2-year changes in carotid total plaque volume (carotid-TPV) and carotid vessel wall volume (carotid-VWV), using three-dimensional ultrasound. RESULTS: Carotid images were available from 174 of the 224 CASCADE participants (67% men; age = 59 yr; HbA1C = 6.8%). Forty-five percent had detectable plaque at baseline. After 2 years, no significant progression in carotid-TPV was observed (water, -1.4 (17.0) mm3, CI (-2.7, 5.5), white-wine, -1.2 (16.9) mm3, CI (-3.8, 6.2), red wine, -1.3 (17.6) mm3, CI (-3.4, 6.0; p = 0.9 between groups)). In post hoc analysis, we divided the 78 participants with detectable baseline carotid plaque into tertiles. Those with the higher baseline plaque burden, whom were assigned to drink wine, reduced their plaque volume significantly after 2 years, as compared to baseline. Two-year reductions in Apo(B)/Apo(A) ratio(s) were independently associated with regression in carotid-TPV (ß = 0.4; p < 0.001). Two-year decreases in systolic blood pressure were independently associated with regression in carotid-VWV (ß = 0.2; p = 0.005). CONCLUSIONS: No progression in carotid-TPV was observed. In subgroup analyses, those with the greatest plaque burden assigned to drink wine may have had a small regression of plaque burden.

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.

Dynamics of intrapericardial and extrapericardial fat tissues during long-term, dietary-induced, moderate weight loss.

Background: In view of evidence linking pericardial fat accumulation with increased cardiovascular disease risk, strategies to reduce its burden are needed. Data comparing the effects of specific long-term dietary interventions on pericardial fat tissue mobilization are sparse.Objective: We sought to evaluate intrapericardial-fat (IPF) and extrapericardial-fat (EPF) changes during weight-loss interventions by different dietary regimens.Design: During 18 mo of a randomized controlled trial, we compared a Mediterranean/low-carbohydrate (MED/LC) diet plus 28 g walnuts/d with a calorically equal low-fat (LF) diet among randomly assigned participants with moderate abdominal obesity. We performed whole-body MRI and volumetrically quantified IPF and EPF among 80 participants to follow the 18-mo changes.Results: The participants [mean age: 48.6 y; mean body mass index (BMI; in kg/m2); 31.7; 90% men] had baseline IPF and EPF (mean ± SD) volumes of 172.4 ± 53.3 mL and 194.9 ± 71.5 mL, respectively. The 18-mo moderate weight loss of 3.7 kg was similar in both groups, but the reduction in waist circumference was higher in the MED/LC group (-6.9 ± 6.6 cm) than in the LF diet group (-2.3 ± 6.5 cm; P = 0.01). After 18 mo, the IPF volume had reduced twice as much in the MED/LC group compared with the LF group [-37 ± 26.2 mL (-22% ± 15%) compared with -15.5 ± 26.2 mL (-8% ± 15%), respectively; P < 0.05, after adjustment for changes in weight or visceral adipose tissue]. The EPF volume had reduced similarly in both groups [-41.6 ± 30.2 mL (-23% ± 16%) in the MED/LC group compared with -37.9 ± 28.3 mL (-19% ± 14%) in the LF group; P > 0.1]. After controlling for weight loss, IPF and EPF volume reduction paralleled changes in lipid profile but not with improved glycemic profile variables: the IPF relative reduction was associated with a decrease in triglycerides (TGs) (ß = 0.090; 95% CI: 0.026, 0.154; P = 0.007) and the ratio of TGs to high-density lipoprotein (HDL) cholesterol (ß = 2.689; 95% CI: 0.373, 5.003; P = 0.024), and the EPF relative reduction was associated with an increase in HDL cholesterol (ß = -0.452; 95% CI: -0.880, -0.023; P = 0.039) and a decrease in total cholesterol and HDL cholesterol (ß = 3.766; 95% CI: 1.092, 6.440; P = 0.007).Conclusions: Moderate but persistent dietary-induced weight loss substantially decreased both IPF and EPF volumes. Reduction of pericardial adipose tissues is independently associated with an improved lipid profile. The Mediterranean diet, rich in unsaturated fats and restricted carbohydrates, is superior to an LF diet in terms of the IPF burden reduction. This trial was registered at clinicaltrials.gov as NCT01530724.

Molecular genetics of familial hypercholesterolemia in Israel-revisited.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the genes for LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type9 (PCSK9). The purpose of the current investigation was to define the current spectrum of mutations causing FH in Israel. METHODS: New families were collected through the MEDPED (Make Early Diagnosis Prevent Early Death) FH program. Molecular analysis of the LDLR, PCSK9 and APOB genes was done using High Resolution Melt and direct sequencing in 67 index cases. A 6-SNP LDL-C gene score calculation for polygenic hypercholesterolaemia was done using TaqMan genotyping. RESULTS: Mean serum cholesterol was 7.48 ± 1.89 mmol/L and the mean serum LDL-C was 5.99 ± 1.89 mmol/L. Mutations in the LDLR and APOB gene were found in 24 cases (35.8%), with 16 in LDLR, none in PCSK9 and one, p.(R3527Q), in the APOB gene, which is the first APOB mutation carrier identified in the Israeli population. Of the LDLR mutations, two were novel; p.(E140A) and a promoter variant, c.-191C > A. The c.2479G > A p.(V827I) in exon 17 of the LDLR gene was found in 8 patients (33.3% of the mutations) with modestly elevated LDL-C, but also in a compound heterozygous patient with a clinical homozygous FH phenotype, consistent with this being a "mild" FH-causing variant. A significantly higher 6-SNP LDL-C score was found in mutation-negative cases compared with a normal Caucasian cohort (p = 0.03), confirming that polygenic inheritance of common LDL-C raising SNPs can produce an FH phenocopy. CONCLUSIONS: The results indicate a different spectrum of genetic causes of FH from that found previously, in concordance with the heterogeneous and changing origins of the Israeli population, and confirm that a polygenic cause is also contributing to the FH phenotype in Israel.

Abdominal fat sub-depots and energy expenditure: Magnetic resonance imaging study.

BACKGROUND & AIMS: We aimed to assess the association between the distinct abdominal sub-depots and resting energy expenditure (REE). METHODS: We performed magnetic resonance imaging (MRI) to quantify abdominal visceral-adipose-tissue (VAT), deep-subcutaneous-adipose-tissue (deep-SAT), and superficial-subcutaneous-adipose-tissue (superficial-SAT). We measured REE by indirect-calorimetry. Non-exercise activity thermogenesis (NEAT) [1-3 metabolic equivalents (METs)] and exercise thermogenesis (activities of 4+METS) were estimated based on 6-days of accelerometry to assess total physical activity energy expenditure (PAEE). RESULTS: We studied 282 participants: 249 men [mean age = 47.4 years, body-mass-index (BMI) = 31 kg/m2, mean VAT proportion from total abdominal fat = 34.5%, mean superficial-SAT proportion from total abdominal fat = 24.3%] and 33 women (mean age = 51.2 years, BMI = 30.1 kg/m2, mean VAT proportion from total abdominal fat = 22.8%, mean superficial-SAT proportion from total abdominal fat = 37.8%). As expected, women had lower REE [by 32.4% (1488 ± 234 kcal/day vs. 1971 ± 257 kcal/day; p < 0.01)] and lower REE/kg [by 8% (19.6 ± 3 kcal/kg vs. 21.2 ± 2 kcal/kg; p < 0.01)] than men. Exercise and total PAEE were positively associated with REE/kg (p < 0.01 for both) and a positive correlation between NEAT and REE/kg was borderline (p = 0.056). Participants, in whom abdominal VAT was the dominant proportional depot, had higher REE (1964 ± 297 kcal/day vs. 1654 ± 352 kcal/day; p < 0.01) and higher REE∖kg (22.2 ± 2.3 kcal/kg/day vs. 19.6 ± 2.5 kcal/kg/day; p < 0.01) than participants in whom superficial-SAT was the largest proportional depot. In multivariate models, adjusted for age, gender and residual BMI, increased VAT proportion was independently associated with higher REE (ß = 0.181; p = 0.05). Likewise, increased VAT proportion (ß = 0.482; p < 0.01) remained independently associated with higher REE/kg. In this model younger age (ß = -0.329; p < 0.01) was associated with higher REE/kg. CONCLUSIONS: Abdominal fat distribution patterns are associated with varying levels of resting energy expenditure, potentially reflecting different metabolic rates of adipose sub-depots and providing an anatomic/anthropometric link to physiological obese sub-phenotypes.

Effects of initiating moderate wine intake on abdominal adipose tissue in adults with type 2 diabetes: a 2-year randomized controlled trial.

OBJECTIVE: To generate evidence-based conclusions about the effect of wine consumption on weight gain and abdominal fat accumulation and distribution in patients with type 2 diabetes. DESIGN: In the 2-year randomized controlled CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, patients following a Mediterranean diet were randomly assigned to drink 150 ml of mineral water, white wine or red wine with dinner for 2 years. Visceral adiposity and abdominal fat distribution were measured in a subgroup of sixty-five participants, using abdominal MRI. SETTING: Ben-Gurion University of the Negev, Soroka-Medical Center and the Nuclear Research Center Negev, Israel. SUBJECTS: Alcohol-abstaining adults with well-controlled type 2 diabetes. RESULTS: Forty-eight participants (red wine, n 27; mineral water, n 21) who completed a second MRI measurement were included in the 2-year analysis. Similar weight losses (sd) were observed: red wine 1·3 (3·9) kg; water 1·0 (4·2) kg (P=0·8 between groups). Changes (95 % CI) in abdominal adipose-tissue distribution were similar: red wine, visceral adipose tissue (VAT) -3·0 (-8·0, 2·0) %, deep subcutaneous adipose tissue (DSAT) +5·2 (-1·1, 11·6) %, superficial subcutaneous adipose tissue (SSAT) -1·9 (-5·0, 1·2) %; water, VAT -3·2 (-8·9, 2·5) %, DSAT +2·9 (-2·8, 8·6) %, SSAT -0·15 (-3·3, 2·9) %. No changes in antidiabetic medication and no substantial changes in energy intake (+126 (sd 2889) kJ/d (+30·2 (sd 690) kcal/d), P=0·8) were recorded. A 2-year decrease in glycated Hb (ß=0·28, P=0·05) was associated with a decrease in VAT. CONCLUSIONS: Moderate wine consumption, as part of a Mediterranean diet, in persons with controlled diabetes did not promote weight gain or abdominal adiposity.

Differential Effect of Initiating Moderate Red Wine Consumption on 24-h Blood Pressure by Alcohol Dehydrogenase Genotypes: Randomized Trial in Type 2 Diabetes.

AIMS: Observational studies report inconsistent associations between moderate alcohol intake and blood pressure (BP). In a sub-study of a larger randomized controlled trial, we assessed the effect of initiating moderate red wine consumption on 24-h BP recordings and the effect of a common genetic variant of alcohol dehydrogenases (ADH) among patients with type 2 diabetes. METHODS: Fifty-four type 2 diabetes, alcohol abstainers were randomized to consume 150 ml/dinner dry red wine or mineral water. Both groups were guided to adhere to a Mediterranean diet, without caloric restriction. We measured 24-h ambulatory BP monitoring (ABPM) at baseline and after 6 months. RESULTS: Participants (age = 57 years; 85% men; mean 24-h BP = 129/77 mm Hg) had 92% 6-month retention. After 6 months of intervention, the average 24-h BP did not differ between the wine and water groups. A transient decrease in BP was observed in the red wine group at midnight (3-4 hours after wine intake: systolic BP: red wine = -10.6mm Hg vs. mineral water = +2.3 mm Hg; P = 0.031) and the following morning at 7-9 am (red wine: -6.2mm Hg vs. mineral water: +5.6mm Hg; P = 0.014). In a second post hoc sub-analysis among the red wine consumers, individuals who were homozygous for the gene encoding ADH1B*2 variant (Arg48His; rs1229984, TT, fast ethanol metabolizers), exhibited a reduction in mean 24-h systolic BP (-8.0mm Hg vs. +3.7 mm Hg; P = 0.002) and pulse pressure (-3.8 mm Hg vs. +1.2 mm Hg; P = 0.032) compared to heterozygotes and those homozygous for the ADH1B*1 variant (CC, slow metabolizers). CONCLUSIONS: Initiating moderate red wine consumption at dinner among type 2 diabetes patients does not have a discernable effect on mean 24-h BP. Yet, a modest temporal BP reduction could be documented, and a more pronounced BP-lowering effect is suggested among fast ethanol metabolizers. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00784433.

Higher visceral adiposity is associated with an enhanced early thermogenic response to carbohydrate-rich food.

BACKGROUND: Studies examining the dynamics of the thermic effect of feeding (TEF) of specific food items and the relationship of TEF to visceral adiposity are limited. METHODS: We measured resting energy expenditure (REE) and early-TEF (40-min postprandial, e-TEF) after 8-h fast by indirect calorimetry in 40 obese men, and imaged abdominal fat tissues by magnetic resonance imaging. Each participant was examined on two occasions, 3-weeks apart. At each examination we measured fasting REE and then postprandial REE following the isocaloric [∼380 kcal] consumption of either 56 gr walnuts [(8% carbohydrates; 84% fat, of which 72% polyunsaturated fat)], or 5-slices (150gr) of whole-grain bread (48% carbohydrates; 32% fat). e-TEF was calculated as the area under the curve between the fasting and postprandial tests. RESULTS: Participants had a mean age of 45 ± 8 years, body-mass-index (BMI) = 31.1 ± 3.8 kg/m(2), total abdominal fat area = 901.4 ± 240 cm(2), visceral fat area (VAT) = 260 ± 102.9 cm(2), fasting REE = 1854 ± 205 kcal, REE/kg = 19.39 ± 1.73 kcal/kg, and respiratory quotient (RQ, CO2 eliminated/O2 consumed) = 0.82 ± 0.04. Individuals who exhibited increased e-TEF (top ΔAUC median) to bread had higher VAT (299 cm(2) vs. 223 cm(2); p = 0.024) and higher BMI (32.4 kg/m(2) vs. 30.0 kg/m(2); p = 0.013), compared to their peers with the lower e-TEF response (ΔAUC below median). As expected, postprandial e-TEF was higher after whole-grain bread consumption [ΔAUC = +14 kcal/40min] compared to walnuts [ΔAUC = -2 kcal/40 min; p < 0.001]. CONCLUSIONS: Higher early thermic effect of high-carbohydrate food, likely reflecting digestion, early absorption and/or sympathetic tone (rather than metabolic utilization (oxidation)), associates with visceral adiposity. Future studies are required to determine if this association represents an added causality between early carbohydrate processing and visceral fat accumulation.

Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes: A 2-Year Randomized, Controlled Trial.

BACKGROUND: Recommendations for moderate alcohol consumption remain controversial, particularly in type 2 diabetes mellitus (T2DM). Long-term randomized, controlled trials (RCTs) are lacking. OBJECTIVE: To assess cardiometabolic effects of initiating moderate alcohol intake in persons with T2DM and whether the type of wine matters. DESIGN: 2-year RCT (CASCADE [CArdiovaSCulAr Diabetes & Ethanol] trial). (ClinicalTrials.gov: NCT00784433). SETTING: Ben-Gurion University of the Negev-Soroka Medical Center and Nuclear Research Center Negev, Israel. PATIENTS: Alcohol-abstaining adults with well-controlled T2DM. INTERVENTION: Patients were randomly assigned to 150 mL of mineral water, white wine, or red wine with dinner for 2 years. Wines and mineral water were provided. All groups followed a Mediterranean diet without caloric restriction. MEASUREMENTS: Primary outcomes were lipid and glycemic control profiles. Genetic measurements were done, and patients were followed for blood pressure, liver biomarkers, medication use, symptoms, and quality of life. RESULTS: Of the 224 patients who were randomly assigned, 94% had follow-up data at 1 year and 87% at 2 years. In addition to the changes in the water group (Mediterranean diet only), red wine significantly increased high-density lipoprotein cholesterol (HDL-C) level by 0.05 mmol/L (2.0 mg/dL) (95% CI, 0.04 to 0.06 mmol/L [1.6 to 2.2 mg/dL]; P < 0.001) and apolipoprotein(a)1 level by 0.03 g/L (CI, 0.01 to 0.06 g/L; P = 0.05) and decreased the total cholesterol-HDL-C ratio by 0.27 (CI, -0.52 to -0.01; P = 0.039). Only slow ethanol metabolizers (alcohol dehydrogenase alleles [ADH1B*1] carriers) significantly benefited from the effect of both wines on glycemic control (fasting plasma glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c) compared with fast ethanol metabolizers (persons homozygous for ADH1B*2). Across the 3 groups, no material differences were identified in blood pressure, adiposity, liver function, drug therapy, symptoms, or quality of life, except that sleep quality improved in both wine groups compared with the water group (P = 0.040). Overall, compared with the changes in the water group, red wine further reduced the number of components of the metabolic syndrome by 0.34 (CI, -0.68 to -0.001; P = 0.049). LIMITATION: Participants were not blinded to treatment allocation. CONCLUSION: This long-term RCT suggests that initiating moderate wine intake, especially red wine, among well-controlled diabetics as part of a healthy diet is apparently safe and modestly decreases cardiometabolic risk. The genetic interactions suggest that ethanol plays an important role in glucose metabolism, and red wine's effects also involve nonalcoholic constituents. PRIMARY FUNDING SOURCE: European Foundation for the Study of Diabetes.

Diets and morbid tissues--history counts, present counts.

Body fat distribution, especially visceral fat accumulation, may contribute more than total fat mass per se to the development of metabolic and cardiovascular disorders. Early prevention highly improves health outcomes later in life, especially when considering such cumulative conditions as atherosclerosis. However, as these processes emerge to be partly reversible, dietary and lifestyle interventions at any age and health condition are greatly beneficial. Given the worldwide abundance of metabolic and cardiovascular disorders, the identification and implementation of strategies for preventing or reducing the accumulation of morbid fat tissues is of great importance for preventing and regressing atherosclerosis. This review focuses on dietary strategies and specific food components that were demonstrated to alter body fat distribution and regression of atherosclerosis. Different properties of various adipose depots (superficial subcutaneous, deep subcutaneous and visceral fat depots) and their contribution to metabolic and cardiovascular disorders are briefly discussed. Visceral obesity and atherosclerosis should be approached as modifiable rather than ineluctable conditions.

Metabolic changes in immigrants from Africa to a Western country: time-lag effects of 20 years since immigration.

BACKGROUND: An increase in the prevalence of type 2 diabetes mellitus occurs in immigrants from developing regions to Western countries. However, the dynamics of these transitions in relation to the duration of residence in the new environment are not clearly defined. METHODS: Data concerning cardiovascular risk factors were retrospectively extracted from medical charts of 736 Ethiopian immigrants and 575 randomly-chosen, age and sex matched non-Ethiopian subjects ("reference group"). Ethiopian immigrants were designated "established" (≥ 20 years of residence), "intermediate" (10-15 years of residence), or "recent" (<10 years of residence). RESULTS: Compared to non-Ethiopians, the age- and sex-adjusted odds ratio (OR) for diabetes was 1.00 (95%CI: 0.66-1.49) for established, 0.55 (95%CI: 0.29-1.03) for intermediate, and 0.15 (95%CI: 0.04-0.50) for recent immigrants (P < 0.001). The corresponding OR for hypertension was 0.94 (95%CI: 0.68-1.31), 0.42 (95%CI: 0.26-0.69), and 0.14 (95%CI: 0.06-0.30) for the established, intermediate, and recent immigrants respectively (P < 0.001). In contrast to the gradual increase in prevalence of diabetes and hypertension, the Ethiopian immigrants maintained their lower body mass index (BMI) (28.7 ± 5 vs 25.5 ± 5 kg/m(2) respectively, P < 0.001) and serum low-density-lipoprotein cholesterol (129 ± 36 vs 118 ± 34 mg/dL, P < 0.001) compared to the non-Ethiopians even after 20 years of residence in Israel. CONCLUSIONS: The prevalence of diabetes and hypertension among the immigrants increased to about half that of the local population within 15 years and became equal to that of the local population after a time-lag of 20 years. These metabolic derangements occurred despite maintaining desirable BMI levels, reinforcing the need for re-defining optimal BMI ranges in relation to the ethnic origin.

Attenuated predictive power of a normal myocardial perfusion scan in young smokers.

BACKGROUND: The negative predictive value of a normal myocardial perfusion image (MPI) for myocardial infarction or cardiac death is very high. However, it is unclear whether a normal MPI, reflecting non-compromised blood flow in the stable state, would have the same prognostic implications in smokers as in patients who do not smoke. METHODS: The incidence of total mortality, cardiovascular mortality, and myocardial infarction was evaluated in 11,812 subjects (14.6% of whom were current smokers at the time of the study) with a normal MPI study and no past history of coronary artery disease during the period 1997 to 2008. RESULTS: During an average follow-up of 72.4 ± 32.4 months the risk for an acute myocardial infarction in current smokers was approximately 50% higher than the corresponding risk in non-smokers, despite a younger average age. Cox proportional regression models show that current smoking was associated with an increased hazard rate for the composite endpoint below age 60 (HR=2.09, 95%CI 1.43-3.07, p<0.001), but not at older ages (HR=1.16, 95% CI 0.81-1.66, p=0.4). CONCLUSIONS: In individuals below age 60, but not at older ages, current smoking is associated with increased short- and long-term risk of cardiac death and acute myocardial infarction even in subjects with a normal MPI.

Nutritional recommendations for cardiovascular disease prevention.

Lifestyle factors, including nutrition, play an important role in the etiology of Cardiovascular Disease (CVD). This position paper, written by collaboration between the Israel Heart Association and the Israel Dietetic Association, summarizes the current, preferably latest, literature on the association of nutrition and CVD with emphasis on the level of evidence and practical recommendations. The nutritional information is divided into three main sections: dietary patterns, individual food items, and nutritional supplements. The dietary patterns reviewed include low carbohydrate diet, low-fat diet, Mediterranean diet, and the DASH diet. Foods reviewed in the second section include: whole grains and dietary fiber, vegetables and fruits, nuts, soy, dairy products, alcoholic drinks, coffee and caffeine, tea, chocolate, garlic, and eggs. Supplements reviewed in the third section include salt and sodium, omega-3 and fish oil, phytosterols, antioxidants, vitamin D, magnesium, homocysteine-reducing agents, and coenzyme Q10.

Renal function following three distinct weight loss dietary strategies during 2 years of a randomized controlled trial.

OBJECTIVE: This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes. RESEARCH DESIGN AND METHODS: In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m(2); mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m(2); mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine <176 µmol/L (eGFR ≥ 30 mL/min/1.73 m(2)) were randomized to low-fat, Mediterranean, or low-carbohydrate diets. The 2-year compliance was 85%, and the proportion of protein intake significantly increased to 22% of energy only in the low-carbohydrate diet (P < 0.05 vs. low-fat and Mediterranean). We examined changes in urinary microalbumin and eGFR, estimated by Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formulas. RESULTS: Significant (P < 0.05 within groups) improvements in eGFR were achieved in low-carbohydrate (+5.3% [95% CI 2.1-8.5]), Mediterranean (+5.2% [3.0-7.4]), and low-fat diets (+4.0% [0.9-7.1]) with similar magnitude (P > 0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR <60 mL/min/1.73 m(2) (+7.1%) versus eGFR ≥ 60 mL/min/1.73 m(2) (+3.7%). In a multivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (ß = -0.211; P = 0.004) and systolic blood pressure (ß = -0.25; P < 0.001) were independently associated with increased eGFR. The urine microalbumin-to-creatinine ratio improved similarly across the diets, particularly among participants with baseline sex-adjusted microalbuminuria, with a mean change of -24.8 (P < 0.05). CONCLUSIONS: A low-carbohydrate diet is as safe as Mediterranean or low-fat diets in preserving/improving renal function among moderately obese participants with or without type 2 diabetes, with baseline serum creatinine <176 µmol/L. Potential improvement is likely to be mediated by weight loss-induced improvements in insulin sensitivity and blood pressure.

Briefly trained medical students can effectively identify rheumatic mitral valve injury using a hand-carried ultrasound.

BACKGROUND: Rheumatic heart disease (RHD) is common and remains a major cause of morbidity, particularly in developing countries. Its diagnosis relies on expertise-dependent echocardiographic studies. We evaluated the accuracy of briefly trained examiners in identifying RHD utilizing a hand-carried cardiac ultrasound (HCU) device. METHODS: Three medical students received 8 hours of training in cardiac ultrasound, focused on assessment of rheumatic valve injury and its complications, using a prototype of HCU device, OptiGo. The students, blinded to the patients' medical condition, performed an auscultation-based physical examination and a focused HCU study on volunteers and patients with known RHD. A standard echocardiography study was used to validate the results. RESULTS: Each student performed a physical examination followed by an HCU study on 45 subjects (mean age 57 ± 14 years, 52% men), 14 of whom (31%) had rheumatic mitral valve injury. The students' averaged sensitivity for diagnosing RHD by HCU examination was 81%, while specificity was 95%. The interrater agreement (kappa) of the 3 students' HCU study and the standard echocardiography examination were between 0.55 and 0.88 (P < 0.01), and among the students themselves between 0.57 and 0.74 (P < 0.01), as students 1 and 2 had better results than student 3. Auscultation-based physical examination rendered low sensitivity (16%) for diagnosing rheumatic valve complications, namely mitral regurgitation and stenosis; however, it improved by 26% when students based their diagnosis on an HCU study. CONCLUSIONS: The ability to detect rheumatic valve injury using a portable ultrasound device by operators who only received brief echocardiographic training is remarkably high. However, the diagnosis of RHD complications is only modest. This result highlights the utility of portable cardiac ultrasound devices operated by basically trained personnel as a valuable diagnostic tool for RHD.