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October 2018
Ahmad Hassan MD, Ronen Jaffe MD, Ronen Rubinshtein MD, Basheer Karkabi MD, David A. Halon MB ChB, Moshe Y. Flugelman MD and Barak Zafrir MD

Background: Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited.

Objectives: To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography.

Methods: A retrospective analysis (2000–2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted.

Results: Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15–5.99) and revascularization (HR 4.30, 95%CI 2.01–9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal < 70 mg/dl.

Conclusions: CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.

June 2015
David Rott MD, Robert Klempfner MD, Ilan Goldenberg MD and David Leibowitz MD

Background: While earlier studies indicated that cholesterol levels decrease significantly after an acute myocardial infarction (MI), a more recent study refuted this observation. 

Objectives: To assess changes in plasma lipid levels after onset of acute MI, and determine important predictors of lipid dynamics.

Methods: We prospectively measured lipid levels of patients who presented with an acute MI. Blood samples were drawn on admission to the hospital (day 1), after fasting at least 12 hours overnight (day 2), and on the 4th day of hospitalization (day 4). 

Results: Of 67 acute MI patients, 30 were admitted for ST elevation MI (STEMI) and 37 for non-STEMI. Both total cholesterol and low density lipoprotein cholesterol (LDL-C) levels decreased significantly (by 9%) in the 24 hours after admission and by 13% and 17% respectively on day 4. High density lipoprotein cholesterol (HDL-C) levels as well as triglycerides did not change significantly. Independent predictors of LDL-C decrease were the presence of diabetes mellitus [odds ratio (OR) 6.73, P = 0.01), and elevated cardiac troponin T (cTnT) levels (OR 1.81, P < 0.04).

Conclusions: LDL-C levels decrease significantly after an acute MI. The reduction is correlated with cTnT levels. Diabetes is a strong independent predictor of LDL-C decrease. In acute MI patients only measurements taken within 24 hours of onset should be used to guide selection of lipid-lowering medication.


March 2015
Firas Rinawi MD, Theodore C. Iancu MD, Corina Hartman MD, Hofit Cohen MD, Havatzelet Yarden-Bilavsky MD, Michal Rozenfeld Bar Lev MD and Raanan Shamir MD
January 2012
Ronit Lubetzky, MD, Galit Zaidenberg-Israeli, MD, Francis B. Mimouni, MD, Shaul Dollberg, MD, Eyal Shimoni, PhD, Yael Ungar, PhD and Dror Mandel, MD

Background: Human milk produced during prolonged lactation (> 1 year) is extraordinarily rich in fat and has a higher energy content than human milk produced during short lactation.

Objectives: To estimate the fatty acid (FA) profile of human milk and to test the hypothesis that the proportion of C12 and C14 (two dietary saturated FA known to most promote hypercholesterolemia) in human milk during prolonged lactation is similar to that in short lactation.

Methods: We conducted a cross-sectional study of 30 mothers of term infants lactating for more than 1 year as compared with 25 mothers of full-term infants who lactated for 2–6 months. Milk was collected by manual expression in mid-breastfeeding.

Results: The two groups did not differ in maternal height, weight, body mass index, diet, infant birth weight and gestational age, but mothers in the prolonged lactation group were significantly older. There was a significant correlation between lactation duration and C12 or C14. The percentage of all FA combined (except for C12 and C14) decreased significantly over time. In contrast, C12:0 and C14:0 combined increased significantly during lactation (R2 = 10.0%, P < 0.03).

Conclusions: Women who lactated for more than 1 year had higher C12 and C14 FA percentages in their milk than women who lactated for 2–6 months.

June 2011
A. Markel

Hypercholesterolemia is one of the main factors in the development of atherosclerotic cardiovascular disease. The advent of statins led to huge progress in the treatment of hypercholesterolemia, yet the proportion of patients with prohibitive lipid values and the high incidence of cardiovascular events despite treatment are still very high. Niacin, one of the older drugs used to treat hyperlipidemia, was shown to reduce low-density lipoprotein-cholesterol (LDL-C) and triglycerides and to markedly increase high-density lipoprotein-cholesterol (HDL-C) levels. This drug came into disuse owing to frequent side effects, mainly flushing, but in recent years a reemergence of its application has occurred, and multiple clinical trials have shown its effectiveness in the treatment of hyperlipidemia and in the reduction in cardiovascular events. New formulations such as extended-release niacin (ERN) have been developed with the purpose of reducing side effects. Lately, a new compound, laropiprant, which selectively antagonizes the prostaglandin 2 (PGD2) receptor responsible for flushing, has been developed. Laropiprant, when combined with ERN,[1] significantly reduces the incidence of flushing. New and ongoing trials will definitively prove in the long term whether this drug combination significantly reduces the severity of flushing and the incidence of cardiovascular events.

[1] ERN = extended release niacin

May 2011
E. Hayim Mizrahi, A. Waitzman, M. Arad and A. Adunsky

Background: Total cholesterol is significantly associated with increased risk of ischemic stroke. Patients with ischemic stroke and high cholesterol levels may show better functional outcome after rehabilitation.

Objectives: To study the possible interrelations between hypercholesterolemia and functional outcome in elderly survivors of ischemic stroke.

Methods: We conducted a retrospective chart review study of consecutive patients (age ≥ 60 years) with acute stroke admitted to a geriatric rehabilitation ward in a university-affiliated hospital. The presence or absence of hypercholesterolemia was based on registry data positive for hypercholesterolemia, defined as total cholesterol ≥ 200 mg/dl (5.17 mmol/L). Functional outcome of patients with hypercholesterolemia (Hchol) and without (NHchol) was assessed by the Functional Independence Measurement scale (FIMTM) at admission and discharge. Data were analyzed by t-test and chi-square test, as well as linear regression analysis.

Results: The complete data for 551 patients (age range 60–96 years)w ere available for final analysis; 26.7% were diagnosed as having hypercholesterolemia. Admission total FIM[1] scores were significantly higher in patients with Hchol[2] (72.1 ± 24.8) compared with NHchol[3] patients (62.2 ± 24.7) (P < 0.001). A similar difference was found at discharge (Hchol 90.8 ± 27.9 vs. NHchol 79.7 ± 29.2, P < 0.001). However, total FIM change upon discharge was similar in both groups (18.7 ± 13.7 vs. 17.6 ± 13.7, P = 0.4). Regression analyses showed that high Mini Mental State Examination scores (β = 0.13, P = 0.01) and younger age (β = -0.12, P = 0.02) were associated with higher total FIM change scores upon discharge. Total cholesterol was not associated with better total FIM change on discharge (β = -0.012, P = 0.82).

Conclusions: Elderly survivors of stroke with Hchol who were admitted for rehabilitation showed higher admission and discharge FIM scores but similar functional FIM gains as compared to NHchol patients. High cholesterol levels may be useful in identifying older individuals with a better rehabilitation potential.

[1] FIM = Functional Independence Measurement

[2] Hcol = hypercholesterolemia

[3] NHchol = non-hypercholesterolemia

January 2009
H. Gilutz, L. Novack, P. Shvartzman, J. Zelingher, D.Y. Bonneh, Y. Henkin, M. Maislos, R. Peleg, Z. Liss, G. Rabinowitz, D. Vardy, D. Zahger, R. Ilia, N. Leibermann and A. Porath

Background: Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease. The Computer-based Clinical Decision Support System provides an opportunity to close these gaps.

Objectives: To study the impact of computerized intervention on secondary prevention of CAD[1].

Methods: The CDSS[2] 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 with CAD (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 recommended to lower lipid level. A significant decrease in low density lipoprotein 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.

[1] CAD = coronary artery disease

[2] CDSS = clinical decision support system

May 2008
M. Shani, J. Dresner, and S. Vinker.

Background: The introduction of more potent statins such as atorvastatin and rosuvastatin in Israel was accompanied by massive advertising about their superiority.

Objectives: To assess the need for switching therapy from older statins to more potent ones among diabetic patients with uncontrolled hypercholesterolemia.

Methods: Data on all diabetic patients over 30 years old attending two urban clinics were extracted and analyzed. For each patient we checked the last low density lipoprotein-cholesterol measurements for the year 2006, the brand and the dose of cholesterol-lowering medications, prescriptions and actual purchasing over a 4 month period prior to the last LDL-C[1] measurement, and whether treatment changes were necessary to achieve the LDL-C target (100 mg/dl or 70 mg/dl).

Results: The study population comprised 630 patients, age 66.7 ± 12.6 years, of whom 338 (53.6%) were women. Of the 533 (84.6%) patients whose LDL-C was measured in 2006, 45 (8.1%) had levels < 70 mg/dl and 184 (33.3%) had levels of 70 mg/dl < LDL-C < 100 m/dl.  The reasons for LDL-C > 100 mg/dl were patients not prescribed cholesterol-lowering drugs (38.3%), partial compliance (27.2%), and under-dosage of statins (15.4%); only 7.7% needed to switch to a more potent statin. Reasons for LDL-C > 70 mg/dl were patients not prescribed cholesterol-lowering drugs (34.3%), partial compliance (22.0%), and under-dosage of statins (26.6%); only 8.7% needed to switch to a more potent statin.

Conclusions: Only a small minority of diabetic patients with uncontrolled hypercholesterolemia need one of the potent statins as the next treatment step. More emphasis on compliance and dose adjustment is needed to achieve the target LDL-C level.

[1] LDL-C = low density lipoprotein-cholesterol

December 2006
E. Zimlichman, M. Szyper-Kravitz, U. Katz and Y. Shoenfeld
August 2006
December 2005
R. Bitzur, D. Harats

Epidemiologic data demonstrate a long-linear realationship between low density lipoprotein-cholesterol levels and risk of coronary heart disease.

November 2005
M. Shechter, R. Beigel, S. Matetzky, D. Freimark, P. Chouraqui.
 Statins play an important role in the treatment and prevention of coronary artery disease and atherosclerosis. Currently, however, despite its important qualities, the use of statin therapy in the treatment of CAD patients ranges only between 30 and 60% in Europe, the United States and Israel. A wide gap still exists between the numerous scientific publications demonstrating the beneficial effects of statins and the low rate of implementing the guidelines in practice. A Medline search up to June 2005 on all prospective, double-blind, randomized clinical trials evaluating the impact of intensive statin therapy (any statin dose >40 mg/daily) on clinical outcomes after a 1 year follow-up revealed only eight trials. In all the eight trials, with a follow-up period of 12–60 months, intensive statin therapy was significantly more effective than and at least as safe as placebo or other standard statin regimens. Thus, based on the current evidence-based medicine, intensive statin therapy enables more patients with CAD to achieve the current National Cholesterol Education Program goal for low density lipoprotein, while ensuring a relatively high safety profile.


June 2005
D. Harats, E. Leibovitz, M. Maislos, E. Wolfovitz, T. Chajek-Shaul, E. Leitersdorf, D. Gavish, Y. Gerber and U. Goldbourt, for the HOLEM study group
 Background: Hypercholesterolemia control status is lacking throughout the western world.

Objectives: To examine whether the treatment recommendations given to ischemic heart disease patients at hospital discharge are compatible with the guidelines of the Israeli Medical Societies and the U.S. National Cholesterol Education Program for coronary artery disease prevention; and to study the effects of brief educational sessions on the adherence of physicians with the guidelines.

Methods: We included consecutive IHD[1] patients admitted to four central hospitals in Israel between 1998 and 2000. The study was conducted in two phases. In phase 1, we reviewed discharge letters to document treatment recommendations given to each patient. In phase 2 we educated the practitioners by reviewing the Israeli Medical Societies and the NCEP[2] guidelines and the quality of their recommendations in phase 1, after which we reevaluated the discharge letters.

Results: The study included 2,994 patients: 627 in phase 1 and 2,367 in phase 2. Of the patients who needed cholesterol-lowering according to their low density lipoprotein levels, 37.4% were not prescribed such drugs at discharge (under-treatment group). This proportion was reduced by education to 26.6% (P < 0.001) in phase 2. Of the treated patients, 65.6% did not reach the target LDL[3] goal in phase 1 (under-dosage group) as compared to 60.2% in phase 2 (P = 0.23). In phase 2 there was an increase in the percent of patients reaching LDL levels <130 mg/day (69.3% vs. 63.8% of patients prescribed medication, P = 0.01), but the percent of patients reaching LDL levels <100 was not different in phase 2 after adjusting for age and gender (the odds ratio for reaching target LDL was 1.16, with 95% confidence interval of 0.95–1.43).

Conclusions: Physician recommendations to IHD patients discharged from hospital were suboptimal. We documented a high proportion of under-treated and under-dosage patients. Brief educational sessions have a beneficial effect on the usage of statins; however, additional effort in guideline implementations is needed.


[1] IHD = ischemic heart disease

[2] NCEP = National Cholesterol Education Program

[3] LDL = low density lipoprotein

August 2004
E. Leibovitz, N. Hazanov, A. Frieman, I. Elly and D. Gavish

Background: Elevated fibrinogen levels are considered a risk factor for the development of atherosclerosis and might be used as a predictor of risk for the development of atherothrombotic events. Several studies have reached equivocal conclusions regarding the effect of statins on fibrinogen.

Objectives: To evaluate the effect of atorvastatin on plasma fibrinogen levels in patients with severe hypercholesterolemia and no other risk factors.

Methods: Twenty-two patients with low density lipoprotein-cholesterol levels above 170 mg/dl (4.40 mmol/L) and with no other risk factors were included in the study. None of the patients had ever received hypolipidemic medication. Patients were followed for 24 weeks (6 office visits 4 weeks apart). During office visits, lipid profile, complete blood count, fibrinogen and C-reactive protein levels were measured.

Results: After 24 weeks of follow-up, total cholesterol decreased by 33% (287 ± 10 to 192 ± 8 mg/dl, P < 0.001), LDL-C[1] by 45% (198 ± 8 to 111 ± 7 mg/dl, P < 0.001) and triglycerides by 21% (189 ± 26 to 138 ± 15 mg/dl, P <0.001). Fibrinogen levels dropped by 18% (355 ± 26 to 275 ± 7 mg/dl, P = 0.01). CRP[2] levels decreased from 0.51 ± 0.15 to 0.28 ± 0.10 mg/dl, but the difference was not statistically significant (P = 0.09). High density lipoprotein, hemoglobin, white blood cell and platelet counts did not change.

Conclusions: We found that atorvastatin reduces plasma fibrinogen in patients with hypercholesterolemia.

[1] LDL-C = low density lipoprotein-cholesterol

[2] CRP = C-reactive protein

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