[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.

Relative fat mass is a better predictor of dyslipidemia and metabolic syndrome than body mass index.

Relative fat mass (RFM) had been recently developed. We aimed to examine RFM predictability to various cardiometabolic risk factors, compared to BMI. METHODS: Observational, cohort study, among patients who visited the Rambam Periodic Examinations Institute (RPEI). We compared the correlation of BMI and RFM to hypertension, impaired fasting glucose, high LDL, low HDL and metabolic syndrome, by gender. RESULTS: During study years, 20 167 patients visited the RPEI and included in the trial. Compared to BMI, RFM showed significantly better predictability (odds ratio [OR], [95% confidence interval (CI), P value]) of high LDL [1.618 (1.441-1.816, P < 0.001) vs. 0.732 (0.67-0.8, P < 0.001) in men; 1.572 (1.377-1.794, P < 0.001) vs. 0.938 (0.849-1.163, P = 0.94) in women], low HDL [2.944 (2.569-3.373, P < 0.001) vs. 2.177 (2-2.369, P < 0.001) in men, 2.947 (2.519-3.448, P < 0.001) vs. 1.9 (1.658-2.176, P < 0.001) in women], high triglycerides [4.019 (3.332-4.847, P < 0.001) vs. 1.994 (1.823-2.181, P < 0.001) in men, 3.93 (2.943-5.247, P < 0.001) vs. 2.24 (1.887-2.62, P < 0.001) in women] and metabolic syndrome [7.479, (4.876-11.47, P < 0.001) vs. 3.263 (2.944-3.616, P < 0.001) in men, 16.247 (8.348-31.619, P < 0.001) vs. 5.995 (5.099-7.048, P < 0.001) in women]. There was no significant difference in the predictability of BMI and RFM to hypertension and diabetes mellitus. CONCLUSION: RFM provides high predictability for dyslipidemias and metabolic syndrome.

Normal body mass index (BMI) can rule out metabolic syndrome: An Israeli cohort study.

The aim of the study was to assess whether body mass index (BMI) can be used as a simple and reliable survey test for metabolic syndrome.The study is an observational cohort study among patients who visited the Rambam Periodic Examinations Institute (RPEI). We analyzed the correlation between obesity indices and presence of metabolic syndrome. We identified the ideal value of BMI for identification of patients at risk for metabolic syndrome. We also described the correlation between different BMI values and its negative predictive value (NPV) for metabolic syndrome.During the study years, 23,993 patients visited the RPEI, and 12.5% of them fulfilled the criteria for metabolic syndrome. Women with metabolic syndrome had higher proportion of obesity, when compared with men (89.9% vs 52.6%; P < .0001). Normal BMI had very high NPV to rule out metabolic syndrome among men and women (98% and 96%, respectively). Using receiver-operating characteristic curve, we found BMI 27 to be the ideal value for identification of metabolic syndrome for the entire cohort (area under the curve [AUC] 0.767, 95% confidence interval [CI] 0.758-0.775, P < .0001), for men (AUC 0.726, 95% CI 0.715-0.738, P < .0001), and for women (AUC 0.843, 95% CI 0.831-0.855, P < .0001). BMI below 30 provided NPV of 91.1% to rule out metabolic syndrome.The BMI as single survey measurement of obesity offers high NPV for metabolic syndrome and can be used by physician and patients for this purpose.

Guaiac faecal occult blood screening in individuals younger than 50 years of age.

To determine the effectiveness of guaiac faecal occult blood tests (gFOBT) in the early detection of colorectal cancer (CRC) within a population of asymptomatic individuals who attended general periodic examinations, and to suggest the recommended age for this screening tool, the electronic database of the periodic examination institute of Rambam Healthcare Campus for the years 2004-2013 was reviewed. Individuals with positive gFOBT results were interviewed for further workup. Proportions of individuals for whom a polyp or CRC was detected were evaluated according to sex and age. 18 858 individuals were examined during the study period, mean age 48 years. The overall gFOBT uptake was 40.8%. Uptake was significantly higher among men and increased with age. Positive gFOBT was detected in 105 individuals (1.4%). The proportion of positive gFOBT was significantly lower among individuals aged 30-50 years than those older than 50 years of age (1.1 and 1.7%, respectively, P=0.005). No positive gFOBT was detected among individuals younger than 30 years of age. Positive gFOBT was higher in men than in women: 1.8 and 0.9% respectively (P=0.002). CRC was detected in six individuals, including two younger than 50 years of age. Polyps were detected in 15 individuals; of these, four were younger than 50 years of age. In the gFOBT-positive group, proportions of polyps and CRC were the same for subgroups according to age. The findings support consideration of annual gFOBT screening from the age of 40 years.

[Factors influencing short-term and long-term prognosis in patients hospitalized for chest pain].

BACKGROUND: The differential diagnosis of chest pain in the emergency department (ED) is broad, but the ability of the physician to distinguish between life-threatening and benign situations is Limited. OBJECTIVES: (1) To evaluate the in-hospital major adverse cardiac events (MACE) among patients admitted to the hospital for chest pain and their five years mortality rate. (2) To find factors in the ED which influence the short- and Long-term prognosis. METHODS: This is a retrospective cohort study. All patients admitted to the hospital only for chest pain, in a five months period, were identified. In-hospital MACE and five years mortality rates were recorded and evaluated in respect to the demographic and personal history of the patients and to tests performed in the emergency department. RESULTS: The MACE rate was Less than 10%. In-hospital mortality was 0.46%. People who had in-hospital MACE were older, with typical chest pain, higher blood CPK level within the normal range, and ST depression on ECG in the ED. The five-year mortality rate was 13.6%. MortaLity was higher among women, older people with past MI, diabetics and in patients with lower hemoglobin and higher creatinine Levels at the ED. CONCLUSIONS: In this group of ED patients with chest pain the MACE rate is small, and mostly appears in older patients with typical chest pain, higher CPK Levels within the normal range and ST depression on ECG. Long term prognosis depended on age, history of diabetes meLlitus and the blood hemoglobin level at the ED.

Cardiovascular risk factors in restless legs syndrome.

We conducted a population-based cross-sectional study to assess prevalence of cardiovascular risk factors in subjects with and without restless legs syndrome (RLS). Adults attending their annual checkup completed the International RLS Study Group questionnaire and underwent an interview by a neurologist. Data from the annual checkup were compared between subjects with and without RLS. The prevalence of RLS was 6.7% (95% CI 5.45-7.95) among 1,537 responders. RLS subjects' blood tests showed significantly higher fasting blood glucose level (P = 0.029), higher prevalence of hypercholesterolemia (P = 0.029) and reduced renal function (P = 0.013), and increased prevalence of low hematocrit (P = 0.008). RLS subjects weighed more (P = 0.029), had a higher BMI (P = 0.033), larger hip circumference (P = 0.033), and were less fit (P = 0.010). To control for interactions among statistical predictors, we also employed multivariate logistic regression models adjusted for age, gender, smoking, BMI, hemoglobin, glucose, HDL/LDL cholesterol, triglycerides, and creatinine. We found that female gender (OR 2.16; 95% CI 1.11-4.17), smoking (OR 1.82; 95% CI, 1.10-3.00), and HDL/LDL cholesterol (OR 0.18; 95% CI 0.034-0.90) were significantly associated with RLS compared with subjects without RLS. RLS was associated with cardiovascular risk factors.

Factor analysis of risk variables associated with low-grade inflammation.

BACKGROUND: Chronic subclinical inflammation, manifesting as elevated levels of inflammatory markers such as C-reactive protein (CRP), predicts future atherothrombotic events. The pathophysiology of low-grade inflammation is complex, and multiple intercorrelated conditions have been associated with elevated CRP. METHODS: Principal factor analysis was used to investigate clustering of variables associated with elevated CRP using data from 1435 subjects without known coronary disease. Components of the metabolic syndrome, uric acid, liver enzymes, pulmonary function tests, smoking status, cardiorespiratory fitness (measured by maximal treadmill test), and high-sensitivity C-reactive protein were determined in each subject. RESULTS: Factor analysis identified three factors, which explained 51.0% of the total variance in the dataset (24.4% factor 1, 17.3% factor 2, and 9.3% factor 3). Based on factor loadings of >or=0.5, these factors were interpreted as (1) "metabolic factor" including BMI, fasting glucose, HDL cholesterol, triglycerides, systolic blood pressure, and uric acid; (2) a cardiorespiratory factor that included fitness level, forced expiratory volume in 1s and sex; and (3) "smoking" factor that included cigarette smoking and age. Each of these factors was significantly associated with the presence of high-risk CRP (>or=3mg/L) in the study population. The ability of a multivariate model that included these three factors to predict high-risk CRP was comparable to a model containing the original 10 variables (area under the receiver-operator characteristics curve 0.7 vs. 0.72, respectively). CONCLUSION: Metabolic perturbations, cardiorespiratory fitness, and smoking are separate and largely independent factors in the pathophysiology of chronic, low-grade inflammation.

Exhaustive exercise modifies oxidative stress in smoking subjects.

BACKGROUND: Exhaustive exercise is associated with increased metabolic rate and accelerated generation of reactive oxygen species. Cigarette smoke also contains oxidants that may participate in the development of atherosclerosis. However, data on the association between exercise and smoking are sparse. METHODS: A homogenous group of 30 young men (15 smokers and 15 nonsmokers; mean age, 23.7 +/- 2.6 years), healthy, trained subjects, were assessed before and after a standard maximal exercise test. RESULTS: Exercise led to increased protein oxidation (carbonyl assay) in both smokers (+17.7%, P < 0.001) and nonsmokers (+19.1%, P < 0.05), elevation in plasma conjugated dienes (+ 157%, P < 0.04), and plasma lipid peroxides (+14%, P < 0.059) in smokers versus nonsmokers after exercise. Plasma antioxidants levels were significantly lower in the smoking group, with reduction in total carotenoids (-36.5%, P < 0.001), vitamin A (-80%, P < 0.001), and vitamin E (-64%, P < 0.002), compared with nonsmokers. A significant rise in leakage of muscle enzymes (CPK, LDH) and urine proteins (microalbumin and myoglobin) occurred in all subjects after exercise. CRP levels were higher in smokers compared with nonsmokers before and after exercise. CONCLUSIONS: Our results suggest that unnoticed interaction exists between smoking and intense exercise, which indicates that smokers are more susceptible to oxidative insults probably due to lower antioxidant capacity.

Inverse association between pulmonary function and C-reactive protein in apparently healthy subjects.

RATIONALE: Increased levels of systemic markers of inflammation have been reported in patients with impaired lung function due to obstructive or restrictive lung disease. OBJECTIVE: We tested the hypothesis that a decline in lung function within the normal range may be associated with a systemic subclinical inflammation. METHODS: Pulmonary function tests, cardiorespiratory fitness, components of the metabolic syndrome, and high-sensitivity C-reactive protein (CRP) were determined in 1,131 subjects without known pulmonary disease. MEASUREMENTS AND MAIN RESULTS: Ninety-six of the study participants (8.5%) had FEV(1) of less than 80% of predicted values. There was a strong inverse association between CRP levels and quartiles of FEV(1). The median CRP levels in nonsmoking participants were 2.5, 1.8, 1.7, and 1.3 mg/L in the first, second, third, and forth FEV(1) quartiles, respectively (p < 0.0001). A similar inverse association was present in smoking subjects (median CRP levels were 3.8, 2.3, 2.0, and 1.9 mg/L in the first, second, third, and fourth FEV(1) quartiles, respectively; p < 0.0001). These associations remained highly significant after adjustment for age, sex, components of the metabolic syndrome, and fitness level (p = 0.0005). CONCLUSIONS: An inverse linear relationship exists between CRP concentrations and measures of pulmonary function in subjects without pulmonary disease and in never-smokers. These results indicate that systemic inflammation may be linked to early perturbations of pulmonary function.

Effect of obesity on the relationship between plasma C-reactive protein and coronary artery stenosis in patients with stable angina.

INTRODUCTION: The association between plasma C-reactive protein (CRP) and the extent of coronary artery disease (CAD) in patients with stable angina remains controversial. Obesity is strongly associated with elevated CRP levels, potentially confounding the relationship between CRP and CAD severity. METHODS AND RESULTS: We studied 830 subjects without CAD and 218 patients with CAD undergoing elective coronary angiography. Geometric means of CRP were computed in a two-way analysis of covariance model in which study participants were stratified into nine groups according to CAD status (no CAD, single-vessel disease or multivessel disease) and tertiles of BMI. There was a significant interaction between CAD and categories of BMI with regard to CRP level (P=0.002). In the lower tertile of BMI, patients with CAD had markedly higher CRP concentration compared to control subjects (1.16, 1.80 and 2.82 mg/L in subjects without CAD, patients with single-vessel disease and patients with multivessel disease, respectively; P=0.003). However, the relationship between CRP and CAD became weaker for patients in the second BMI tertile (P=0.15), whereas no significant relationship was observed for patients in the third BMI tertile (P=0.75). In patients undergoing coronary angioplasty (n=195), BMI was independently related to the magnitude of the angioplasty-induced CRP elevations (P=0.002). CONCLUSION: The level of obesity is essential to the interpretation of the relationship between CRP and severity of CAD. The production of inflammatory mediators with increasing levels of obesity becomes the dominant determinant of plasma CRP levels and masks the vascular contribution due to CAD.

Association between elevated liver enzymes and C-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome.

OBJECTIVE: The objective of this study was to test whether the frequent association between liver enzyme elevations and various components of the metabolic syndrome is associated with higher C-reactive protein (CRP) levels. METHODS AND RESULTS: Alanine aminotransferase (ALT), alkaline phosphatase (Alk-P), and high-sensitivity CRP were measured in 1740 subjects. Adjusted geometric mean CRP was calculated for subjects with normal and elevated ALT and for subjects with normal and elevated Alk-P, adjusting for age, sex, smoking, physical activity, body mass index, fasting glucose, triglycerides, the presence of hypertension and low HDL cholesterol, and use of aspirin or hormone replacement therapy. Adjusted CRP levels were higher in subjects with elevated ALT (2.21 versus 1.94 mg/L, P=0.028) or elevated Alk-P (2.58 versus 1.66 mg/L, P<0.0001). Logistic regression showed that compared with subjects with normal liver function tests, the adjusted odds for high-risk CRP (>3 mg/L) were significantly higher in subjects with elevated ALT (OR, 1.5; 95% CI, 1.2 to 1.9, P=0.002) or elevated Alk-P (OR, 2.1; 95% CI, 1.7 to 2.6, P<0.0001). CONCLUSIONS: Elevations of liver enzymes are associated with higher CRP concentrations. Hepatic inflammation secondary to liver steatosis is a potential contributor to the low-grade inflammation associated with the metabolic syndrome.

The association between cardiorespiratory fitness and C-reactive protein in subjects with the metabolic syndrome.

OBJECTIVES: We sought to study relationship between cardiorespiratory fitness and C-reactive protein (CRP) in subjects with the metabolic syndrome. BACKGROUND: Recent studies have shown an association between the metabolic syndrome and chronic subclinical inflammation, as determined by elevated CRP. Cardiorespiratory fitness is associated with a lower risk of diabetes and improved insulin resistance. METHODS: Physical fitness was assessed in 1,640 subjects using the Bruce treadmill protocol and expressed as maximal metabolic equivalents. The level of CRP was measured using a high-sensitivity assay. RESULTS: Geometric mean CRP was calculated across quartiles of fitness after adjustment for age, gender, smoking, use of medications, and coronary disease. A strong inverse trend toward decreasing CRP levels with increasing fitness quartiles was present in subjects without metabolic abnormalities, subjects with one or two metabolic abnormalities, and subjects with the metabolic syndrome (all p

C-Reactive protein is inversely related to physical fitness in middle-aged subjects.

INTRODUCTION: Physical fitness has a protective effect with regard to the risk of developing coronary disease or diabetes. C-reactive protein (CRP) levels are directly related to increased risk of coronary disease and diabetes. However, data on the association between physical fitness and CRP are sparse. METHODS: Physical fitness was assessed in a population-based cross-sectional study (n = 892; age 50 +/- 9 years) using the Bruce treadmill protocol. CRP was measured using a high-sensitivity assay. RESULTS: Geometric mean CRP levels were calculated across quartiles of physical fitness after adjustment for age, gender, body mass index, smoking habit, presence of diabetes and hypertension, HDL cholesterol and triglyceride levels, and use of hormone replacement therapy, statins, and aspirin. CRP levels decreased with increasing quartiles of fitness (P for trend <0.0001). When used as a continuous variable in a stepwise linear regression model, the geometric mean of CRP decreased by 0.061 mg/L (95% confidence interval (CI) 0.034-0.089 mg/L) for each 1 unit increase in metabolic equivalents (METs). Multivariate logistic regression models showed that compared to subjects in the lowest fitness quintile, subjects in the highest fitness quintile had significantly lower adjusted odds of having a high-risk (>3 mg/L) CRP level (OR 0.53; 95% CI 0.39-0.71, P = 0.007). CONCLUSION: CRP concentration decreases continuously with increasing levels of physical fitness. The health-related salutary effects of physical fitness may be mediated, in part, through an antiinflammatory mechanism.

[Cardiovascular risk factors assessment in Rambam Center Preventive Medicine].

Atherosclerosis, expressing itself as cardiovascular disease, is the first cause of death in Israel, in people over 35 years of age. The main risk factors for atherosclerosis are generally known, and amendable, resulting in a decrease in morbidity and mortality rates. In our present article we investigate the prevalence of major atherosclerosis risk factors in the population being examined in the Rambam Center of Preventive Medicine. This is a young population, usually considered healthy. The prevalence of the major risk factors is high, and a large portion of the population is at high risk of developing cardiovascular disease. Identifying the people at high risk of developing cardiovascular disease and of instigating preventive measures is of utmost importance.

Plasma endothelin levels as a function of coronary artery manipulation during balloon angioplasty and high-speed rotational atherectomy.

This study was conducted to test the hypothesis that endothelin levels may be related to the coronary artery manipulation during balloon angioplasty (BA) or rotational atherectomy (RA). Blood endothelin levels were measured in 35 patients who underwent BA and in 11 patients who underwent RA followed by adjunctive balloon angioplasty. Arterial and venous levels were measured before, immediately after, and 24 h after the procedure. The levels were then related to the number of balloon inflations, the total inflation time and the maximal pressure in the balloon during inflation. There were no significant differences between groups or time periods. However, 24 h after BA the endothelin plasma levels in venous blood were directly related to the number of balloon inflations (r 3 0.49; P 3 0.03), to the total inflation time (r 3 0.67; P 3 0.005) and to the maximal inflation pressure (r 3 0.71; P 3 0.001). No such correlation was found in venous blood immediately after BA, either in arterial blood or in the RA group. It can be concluded that plasma endothelin levels do not change significantly after balloon angioplasty; however, venous endothelin levels 24 h after BA are related to procedural parameters, reflecting endothelial damage, which may determine the post-angioplasty late results.