[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.

[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 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.

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.

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.

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.

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.

[Participation in cardiac rehabilitation after coronary bypass surgery: good news, bad news].

Cardiac rehabilitation programs have the potential to decrease morbidity and mortality and increase quality of life after acute coronary events and coronary bypass surgery (CABG). Unfortunately, the proportion of eligible patients that participate in cardiac rehabilitation remains low, despite coverage of such programs by the Israeli National Health Insurance. A low participation rate is especially prominent in women, elderly, minorities and low socioeconomic classes. In this edition of Harefuah, Gendler et at conducted an interventional study aimed at increasing the participation of patients in cardiac rehabilitation programs after CABG in 5 cardiothoracic wards across Israel. They interviewed 489 patients in the intervention arm and 472 patients in the control arm before surgery and a year later. The intervention included dissemination of information on cardiac rehabilitation to the medical staff and patients. Following the intervention, cardiac rehabilitation increased almost twofold in veteran-Israeli males and females. Although it increased significantly in USSR-born male immigrants, their absolute rate of participation remained low (13.6%). No USSR-born female participated in rehabilitation, either before or after the intervention. The good news is that a simple, inexpensive intervention can increase participation in cardiac rehabilitation after CABG surgery. The bad news is that this potentially lifesaving activity remains unattended by most USSR-born immigrants, and particularly by females. Additional research is required to explore the cultural, social and economic barriers of this phenomenon.

[Prevention and treatment of atherosclerosis and cardiovascular diseases].

Atherosclerosis is one of the main causes of morbidity and mortality world-wide and specifically in Israel. These guidelines update the previous guidelines of the Israeli Society for Research, Prevention and Treatment of Atherosclerosis, published in 2005. The need for an update is based on new scientific data published in recent years necessitating changes in the recommendations for preventing and treating atherosclerosis. These guidelines were written in collaboration between all the societies outlined here and the content of this statement was approved by the delegates of these societies. The recommendations were written taking into consideration guidelines published by other international medical societies and also the specific needs of the Israeli medical system. Due to limitations of space, in the current paper we present: assessment of cardiovascular risk, smoking cessation and the treatment of dyslipidemia. Other sections including: recommendations to the general population, nutritional and physical activity recommendations, treatment of hypertension, prevention of ischemic stroke and the metabolic syndrome are available at http://www.ima.org.il/harefuah.

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.

Dietary intervention to reverse carotid atherosclerosis.

BACKGROUND: It is currently unknown whether dietary weight loss interventions can induce regression of carotid atherosclerosis. METHODS AND RESULTS: In a 2-year Dietary Intervention Randomized Controlled Trial-Carotid (DIRECT-Carotid) study, participants were randomized to low-fat, Mediterranean, or low-carbohydrate diets and were followed for changes in carotid artery intima-media thickness, measured with standard B-mode ultrasound, and carotid vessel wall volume (VWV), measured with carotid 3D ultrasound. Of 140 complete images of participants (aged 51 years; body mass index, 30 kg/m(2); 88% men), higher baseline carotid VWV was associated with increased intima-media thickness, age, male sex, baseline weight, blood pressure, and insulin levels (P<0.05 for all). After 2 years of dietary intervention, we observed a significant 5% regression in mean carotid VWV (-58.1 mm(3;) 95% confidence interval, -81.0 to -35.1 mm(3); P<0.001), with no differences in the low-fat, Mediterranean, or low-carbohydrate groups (-60.69 mm(3), -37.69 mm(3), -84.33 mm(3), respectively; P=0.28). Mean change in intima-media thickness was -1.1% (P=0.18). A reduction in the ratio of apolipoprotein B(100) to apolipoprotein A1 was observed in the low-carbohydrate compared with the low-fat group (P=0.001). Participants who exhibited carotid VWV regression (mean decrease, -128.0 mm(3); 95% confidence interval, -148.1 to -107.9 mm(3)) compared with participants who exhibited progression (mean increase, +89.6 mm(3); 95% confidence interval, +66.6 to +112.6 mm(3)) had achieved greater weight loss (-5.3 versus -3.2 kg; P=0.03), greater decreases in systolic blood pressure (-6.8 versus -1.1 mm Hg; P=0.009) and total homocysteine (-0.06 versus +1.44 mumol/L; P=0.04), and a higher increase of apolipoprotein A1 (+0.05 versus -0.00 g/L; P=0.06). In multivariate regression models, only the decrease in systolic blood pressure remained a significant independent modifiable predictor of subsequent greater regression in both carotid VWV (beta=0.23; P=0.01) and intima-media thickness (beta=0.28; P=0.008) levels. CONCLUSIONS: Two-year weight loss diets can induce a significant regression of measurable carotid VWV. The effect is similar in low-fat, Mediterranean, or low-carbohydrate strategies and appears to be mediated mainly by the weight loss-induced decline in blood pressure. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00160108.

Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.

BACKGROUND: Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates. METHODS: In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie. RESULTS: The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels). CONCLUSIONS: Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108.)

Physician adherence to the dyslipidemia guidelines is as challenging an issue as patient adherence.

BACKGROUND: A wide therapeutic gap exists between evidence-based guidelines and their practice in the primary care, which is primarily attributed to physician and patient adherence. OBJECTIVE: This study aims to differentiate physician and patient adherence to dyslipidemia secondary prevention guidelines and various factors affecting it. METHODS: A post hoc analysis of data collected by a prospective cluster randomized trial with 7041 patients diagnosed with clinical atherosclerosis requiring secondary prevention of dyslipidemia and 127 primary care physicians over an 18-month period. Adherence was measured by physicians' and patients' actions taken according to the guidelines and correlated using multivariate logistic regressions. RESULTS: Physician adherence was 36.9% for lipid profile screening, 27.6% for pharmacotherapy up-titration and 21.0% for pharmacotherapy initiation. Physician adherence was positively correlated with frequent patient visits [odds ratios (OR = 1.304)], having more dyslipidemic patients (OR = 1.304) and treating immigrants (OR = 1.268). Patient adherence was 83.8%, 71.9% and 62.6% for medication up-titration, lipid profile screening and pharmacotherapy initiation, respectively. Patient adherence was affected by attending clinics with many dyslipidemic patients (OR = 1.542), being older (OR = 1.271) and being treated by a male physician (OR = 0.870). CONCLUSIONS: We learn from this study that (i) physician non-adherence was a major cause for the failure to follow guidelines, (ii) pharmacotherapy initiation was the most challenging issue to tackle and (iii) greater adherence occurred mainly in high volume conditions (patients and visits). Practical implications are designated focus on metabolic condition prevention in primary care by cardiologists or primary care clinics specializing in metabolic conditions and the need to facilitate more frequent follow-up visits.

Risk factors and outcome of acute myocardial infarction in Bedouins living in permanent compared to unrecognized villages in southern Israel.

BACKGROUND: The incidence and prevalence of coronary heart disease (CHD) among Bedouins living in the Negev region were very low until the 1960s. During the past 50 years this pattern has changed: in parallel to the changes in lifestyle and nutrition in the Bedouin population, a rapid increase in incidence and mortality from CHD occurred. The relationship between the rise in CHD incidence and the degree of urbanization in this population has not been investigated to date. The study hypothesis was that the prevalence of risk factors and the outcome of myocardial infarction in Bedouins differ between those settled in permanent villages and those remaining in unrecognized villages. OBJECTIVES: To compare the prevalence of cardiovascular risk factors, clinical characteristics, and in-hospital management of a first acute myocardial infarction (AMI) in two Bedouin groups: those residing in permanent villages versus those residing in unrecognized villages. METHODS: We conducted a retrospective analysis of in-hospital data of 352 patients admitted with a first AMI during the period 1997-2003 to Soroka Medical Center, the only medical facility in the region. RESULTS: There were no differences between the two groups regarding the major cardiovascular risk factors and outcome. A relatively greater number of patients from urban areas underwent catheterization of any sort during their hospitalization (primary, rescue, and risk stratification; P = 0.038). No significant difference was found between the two groups in the type of catheterization performed (P = 0.279). CONCLUSIONS: We found no differences in the clinical characteristics and in-hospital management of patients with AMI between Bedouins residing in permanent villages versus unrecognized villages.

Adherence by primary care physicians to guidelines for the clinical management of dyslipidemia.

BACKGROUND: There is a wide treatment gap between evidence-based guidelines and their implementation in primary care. OBJECTIVE: To evaluate the extent to which physicians "literally" follow guidelines for secondary prevention of dyslipidemia and the extent to which they practice "substitute" therapeutic measures. METHODS: We performed a post hoc analysis of data collected in a prospective cluster randomized trial. The participants were 130 primary care physicians treating 7745 patients requiring secondary prevention of dyslipidemia. The outcome measure was physician literal adherence or substitute adherence. We used logistic regressions to evaluate the effect of various clinical situations on literal and substitute adherence. RESULTS: Literal adherence was modest for ordering a lipoprotein profile (35.1%) and for pharmacotherapy initiations (26.0%), but rather poor for drug up-titrations (16.1%) and for referrals for specialist consultation (3.8%). In contrast, many physicians opted for substitute adherence for up-titrations (75.9%) and referrals for consultation (78.7%). Physicians tended to follow the guidelines literally in simple clinical situations (such as the need for lipid screening) but to use substitute measures in more complex cases (when dose up-titration or metabolic consultation was required). Most substitute actions were less intense than the actions recommended by the guidelines. CONCLUSIONS: Physicians often do not blindly follow guidelines, but rather evaluate their adequacy for a particular patient and adjust the treatment according to their assessment. We suggest that clinical management be evaluated in a broader sense than strict guideline adherence, which may underestimate physicians' efforts.

Computerized community cholesterol control (4C): meeting the challenge of secondary prevention.

BACKGROUND: Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease. The Computer-based Clinical Decision Support System provides an opportunity t close these gaps. OBJECTIVES: To study the impact of computerized intervention on secondary prevention of CAD. METHODS: The CDSS was programmed to automatically detect patients with CAD and to evaluate the availability of an updated lipoprotein profile and treatment with lipid-lowering drugs. The program produced automatic computer-generated monitoring and treatment recommendations. Adjusted primary clinics were randomly assigned to intervention (n=56) or standard care arms (n=56). Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment. Compliance and lipid levels were monitored. The study group comprised all patients with CAD who were alive at least 3 months after hospitalization. RESULTS: Follow-up was available for 7448 patients (median 19.8 months, range 6-36 months). Overall, 51.7% of patients were adequately screened, and 55.7% of patients were compliant with treatment to lower lipid level. In patients with initial low density lipoprotein >120 mg/dl, a significant decrease in LDL levels was observed in both arms, but was more pronounced in the intervention arm: 121.9 +/- 34.2 vs. 124.3 +/- 34.6 mg/dl (P < 0.02). A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs, 37% vs. 40.9% (P < 0.001). CONCLUSIONS: This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines, presenting a major obstacle to implementing effective secondary prevention. Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation.

Changes in triglyceride levels and risk for coronary heart disease in young men.

BACKGROUND: Current triglyceride levels might be only a weak predictor of risk for coronary heart disease (CHD). OBJECTIVE: To assess the association between changes over time in fasting triglyceride levels and CHD risk in young adults. DESIGN: Follow-up study over 5.5 years after 2 measurements of fasting triglycerides 5 years apart. SETTING: The Staff Periodic Examination Center of the Israel Defense Forces, Zrifin, Israel. PATIENTS: 13,953 apparently healthy, untreated, young men (age 26 to 45 years) with triglyceride levels less than 3.39 mmol/L (<300 mg/dL). MEASUREMENTS: Two triglyceride measurements (at enrollment [time 1] and 5 years later [time 2]), lifestyle variables, and incident cases of angiography-proven CHD. RESULTS: Within 5.5 years, 158 new cases of CHD were identified. The multivariate model was adjusted for age; family history; fasting glucose; high-density lipoprotein cholesterol; blood pressure; body mass index; and changes between time 1 and time 2 in body mass index, physical activity, smoking status, and habit of eating breakfast. Investigators categorized triglyceride levels according to low, intermediate, and high tertiles (as measured at time 1 and time 2 [expressed as tertile at time 1/tertile at time 2]). The risk for CHD in men with high-tertile triglyceride levels at time 1 changed depending on the tertile at time 2 (hazard ratios, 8.23 [95% CI, 2.50 to 27.13] for high/high, 6.84 [CI, 1.95 to 23.98] for high/intermediate, and 4.90 [CI, 1.01 to 24.55] for high/low, compared with the stable low/low group). The risk for CHD in men with low-tertile levels at time 1 also changed depending on the tertile at time 2 (hazard ratios, 3.81 [CI, 0.96 to 15.31] for low/intermediate and 6.76 [CI, 1.34 to 33.92] for low/high, compared with the stable low/low group). LIMITATIONS: Participants were healthy and had a low incidence rate of CHD. The study was observational. CONCLUSIONS: Two triglyceride measurements obtained 5 years apart may assist in assessing CHD risk in young men. A decrease in initially elevated triglyceride levels is associated with a decrease in CHD risk compared with stable high triglyceride levels. However, this risk remains higher than in those with persistently low triglyceride levels.

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.

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.