PONENCIA ACTUALIZACIÓN EN LÍPIDOS Y ARTERIOSCLEROSIS UPDATE 2011, REALIZADA POR EL DOCTOR LLUIS MASANA DURANTE LA XIV JORNADA DE LA XARXA CATALANA DE LÍPIDS i ARTERIOSCLEROSI

1. XIV JORNADA DE LA XARXA CATALANA DE LÍPIDS i ARTERIOSCLEROSI
ACTUALITZACIÓN EN LÍPIDOS Y ARTERIOSCLEROSIS
UPDATE 2011
LLUÍS MASANA
HOSPITAL UNIVERSITARI SANT JOAN
UNIVERSITAT ROVIRA & VIRGILI
CIBERDEM-IISPV
REUS

2. Búsqueda PubMed
“Atherosclerosis AND Lipoprotein”
Limits: 1 year
English or Spanish
+ búsqueda específica en NEJM, Circulation, Diabetes
Estudios básicos y clínicos pero de interés clínico
Estudios en humanos
Selección totalment sesgada por las preferencias del “speaker”
Total 1269 artículos; Primera selección 84 pdf; Incluidos 44

3. CÉLULAS, MOLÉCULAS, LÍPIDOS Y ARTERIOSCLEROSIS

4. The Human Plasma Lipidome
N Engl J Med 2011;365:1812-23.

5. Autophagy Regulates Cholesterol Efflux from Macrophage
Foam Cells via Lysosomal Acid Lipase
Cell Metabolism 2011, 13: 655-667

6. Metabolism: Let them eat fat
Nature:477:166–167; 2011

7. MicroRNA Modulation of Cholesterol Homeostasis
Arterioscler Thromb Vasc Biol. 2011;31:2378-2382

8. MicroRNAs are Transported in Plasma and Delivered to Recipient Cells
by High-Density Lipoproteins
Nat Cell Biol. 2011 April ; 13(4): 423–433. doi:10.1038/ncb2210.

9. MicroRNAs are Transported in Plasma and Delivered to Recipient Cells
by High-Density Lipoproteins
Nat Cell Biol. 2011 April ; 13(4): 423–433. doi:10.1038/ncb2210.

10. OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of
MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases
FASEB J. 25, 1718–1728 (2011)

11. GUÍAS CLÍNICAS Y CONSENSOS

17. Assessment and Treatment of Cardiovascular Risk in Prediabetes:
Impaired Glucose Tolerance and Impaired Fasting Glucose
Because prediabetes and diabetes are
CV risk equivalents,the goals for LDL-C
level should be similar in both groups:
LDL-C 70 mg/dL in patients with
prediabetes/diabetes with known CVD
or without CVD but with 1 additional
major CV risk factor;
and LDL-C 100 mg/dL in patients with
prediabetes/diabetes without CVD
and without any major CV risk factor.
The TZDs—especially at low doses and
in combination with metformin—
represent a rational choice to
ameliorate insulin resistance, prevent
the progression of IGT/IFG to type 2
diabetes, and possibly to reduce the
high incidence of CV events in
individuals with prediabetes and type 2
diabetes
Am J Cardiol 2011;108[suppl]:3B–24B

18. FÁRMACOS, PAUTAS TERAPÉUTICAS Y ENSAYOS CLÍNICOS

19. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in
patients with chronic kidney disease (Study of Heart and Renal Protection):
a randomised placebo-controlled trial
The Lancet, 2011; 377, 2153-2154

20. Safety of Anacetrapib in Patients with or at High Risk for Coronary Heart Disease
N Engl J Med Nov 2010

21. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-
invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial
Lancet 2011;378: 1547-59

22. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-
invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial
Lancet 2011;378: 1547-59

23. dal-VESSEL
FMD: Observed change from baseline. No adverse effect of dalcetrapib
2.00 Placebo (n=234)
1.75 Dalcetrapib 600 mg (232)
Change from baseline in % FMD
1.50
1.25
1.00
0.75
0.50
0.25
0.00
-0.25
-0.50
0 12 36
Week
Data presented as least squares mean (SE) absolute change from baseline in %FMD at weeks 12 and 36
Lüscher et al. ESC 2011.
23

24. AIM-HIGH STUDY
-
FDA Statement on the AIM-HIGH Trial
[05-26-2011]
The U.S. Food and Drug Administration (FDA) will conduct a comprehensive review of the results from the clinical trial called the Atherothrombosis Intervention in Metabolic
Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) once they are available. The AIM-HIGH trial studied whether raising high-density
lipoprotein (HDL) or "good" cholesterol levels in patients who have a history of cardiovascular disease and well-controlled low-density lipoprotein (LDL) or "bad" cholesterol
levels could lower the rate of major adverse cardiovascular events (MACE). In AIM-HIGH, MACE was defined as cardiovascular death, non-fatal heart attack, ischemic stroke,
hospitalizations for acute coronary syndrome in which there is insufficient blood flow to the heart, or revascularization procedures to improve blood flow in the arteries of the
heart and brain.
In this trial, all study participants were given standard therapy with simvastatin 40 mg per day, and then randomly assigned to receive either extended-release niacin 1500-2000
mg per day or placebo. In the first year of the trial, the simvastatin dose could be adjusted, or a second LDL cholesterol-lowering drug, ezetimibe 10 mg, could be added, to
achieve the target LDL-cholesterol goal of 40-80 mg/dL.
The trial was started in September 2005, but was stopped early due to the lack of incremental benefit on cardiovascular risk reduction in the extended-release niacin plus
simvastatin treatment group over simvastatin alone. In addition, a small, unexplained, increase in the rate of ischemic stroke was noted in the simvastatin plus extended-release
niacin group compared to the simvastatin alone group (28 strokes [1.6%] vs. 12 strokes [0.7%], respectively). Nine of the ischemic strokes in the simvastatin plus extended-
release niacin group occurred in participants who had stopped taking their niacin for at least 2 months and up to 4 years before their stroke. Therefore, it is unclear what role, if
any, niacin contributed to this imbalance in ischemic stroke.
At this time, FDA has made no new conclusions or recommendations regarding the use of extended-release niacin alone or in combination with simvastatin or other statins.
The Agency will conduct a comprehensive review of the AIM-HIGH trial data as soon as they become available to determine their impact on the approved indications for
extended-release niacin.
High-dose niacin is a prescription drug that is used along with diet and exercise to manage cholesterol and fat (triglyceride) levels in the blood. It is also indicated as a
monotherapy to lower the risk of heart attacks in patients who have had a heart attack and have high cholesterol. High-dose niacin is available as an extended-release tablet
under the brand-name Niaspan, and is also available in combination with simvastatin under the brand-name Simcor, and in combination with lovastatin under the brand-name
Advicor.
Healthcare professionals should consider the available clinical information on high-dose extended-release niacin and statin drugs when deciding what cholesterol-lowering
medication to prescribe.
Patients should not stop taking their current medications without talking to their healthcare professional.
The Agency will update the public with any new recommendations or conclusions when its review of the AIM-HIGH trial data is complete.
The AIM-HIGH trial was funded by the National Heart, Lung, and Blood Institute (NHLBI). To view the NHLBI's press release, please visit NIH stops clinical trial on combination
cholesterol treatment1.
-
Related Information
•Simvastatin (marketed as Zocor) Information2
•NIH stops clinical trial on combination cholesterol treatment3
NIH Press Release - 5/26/2011

25. Weighing the Benefits of High-Dose Simvastatin against the Risk of Myopathy
10.1056/nejmp1106689 2 nejm.org

26. The relationship of vitamin D deficiency to statin myopathy
abstract
Objective: Our goal was to examine the interaction between vitamin D and statins and the possible role
of vitamin D deficiency in statin myopathy.
Background: The vitamin D receptor is present in skeletal muscle and vitamin D deficiency can cause
myopathy. Statins (3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors) are generally well tolerated,
but have been associated with a spectrum of skeletal muscle complaints, ranging from myalgia and
asymptomatic mild elevations of creatine kinase (CK) to rhabdomyolysis. There has been recent interest
in the possible interaction between statin myopathy and vitaminDdeficiency.Weperformed a systematic
medical literature review to examine this possible relationship.
Methods: We identified English language articles relating statins, vitamin D and statin myopathy via a
PubMed search through July 2010. Articles pertinent to the topic were reviewed in detail.
Results/conclusions: Our review suggests that some
but not all statins increase 25(OH) D
levels. Two crosssectional studies have associated vitamin D deficiency with statin-
associated myalgias, and suggested that that increasing vitamin D levels can reverse the myalgia.
Nevertheless, given the quality and paucity of studies examining this possibility, additional studies are
needed to examine the potential role of vitamin D deficiency in statin myopathy. It is presently premature to
recommend vitamin D supplementation as treatment for statin associated muscle complaints in the absence
of low vitamin D levels although such supplementation could be tried in patients with
deficient or reduced vitamin D levels.
Atherosclerosis 215 (2011) 23–29

27. Colesevelam HCl Added to Background Metformin Therapy in Patients With
Type 2 Diabetes Mellitus: A Pooled Analysis From Three Clinical Studies
Endocr Pract 2011 AACE.DOI:10.4158/EP11218.OR

28. ASPECTOS EPIDEMIOLÓGICOS DEL RIESGO CARDIOVASCULAR

29. Diabetes Mellitus, Fasting Glucose, and Risk of Cause-Specific Death
The Emerging Risk Factors Collaboration*
N Engl J Med 2011;364:829-41.

30. Diabetes Mellitus, Fasting Glucose, and Risk of Cause-Specific Death
The Emerging Risk Factors Collaboration*
N Engl J Med 2011;364:829-41.

31. Adolescent BMI Trajectory and Risk of Diabetes versus Coronary Disease
N Engl J Med 2011;364:1315-25.

32. Trends in the Risk for CHD Among Adults With Diagnosed Diabetes in the U.S.
Findings from the National Health and Nutrition Examination Survey, 1999–2008
DIABETES CARE, VOLUME 34, JUNE 2011

34. Changes in atherosclerotic plaques induced by inhalation of diesel exhaust
Atherosclerosis 216 (2011) 299–306

35. Traffic Air Pollution and Oxidized LDL
PLoS ONE 6(1): e16200. doi:10.1371/journal.pone.0016200

36. MARCADORES DE RIESGO CARDIOVASCULAR

37. Decreased circulating lipoprotein-associated phospholipase A2 levels are
associated with coronary plaque regression in patients with ACS
Atherosclerosis xxx (2011) xxx– xxx

38. Lipoprotein-associated phospholipase A2 testing usefulness among
patients with symptomatic intracranial atherosclerotic disease
Andreu Massot et al. Atherosclerosis 218 (2011) 181– 187

39. Predictive value of remnant lipoprotein for cardiovascular events in patients
with coronary artery disease after achievement of LDL-cholesterol goals
Atherosclerosis 218 (2011) 163– 167

40. IMAGEN , FUNCIÓN VASCULAR Y ATEROSCLEROSIS SUBCLÍNICA

41. Predictors of Coronary Heart Disease Events Among Asymptomatic Persons
With Low Low-Density Lipoprotein Cholesterol
MESA (Multi-Ethnic Study of Atherosclerosis)
J Am Coll Cardiol 2011;58:364–74

42. Predictors of Coronary Heart Disease Events Among Asymptomatic Persons
With Low Low-Density Lipoprotein Cholesterol
MESA (Multi-Ethnic Study of Atherosclerosis)
J Am Coll Cardiol 2011;58:364–74

43. Aortic Pulse Wave Velocity Is Associated With
Measures of Subclinical Target Organ Damage
JACC:CARDIOVASCULARIMAGING,VOL.4,NO.7,2011

44. Carotid-Wall Intima–Media Thickness and Cardiovascular Events
n engl j med 365;3 nejm.org july 21, 2011

45. Evaluation of subclinical atherosclerosis by computed tomography
coronary angiography and its association with risk factors
in familial hypercholesterolemia
Atherosclerosis 213 (2010) 486–491

46. HDL

47. Cholesterol Efflux Capacity, High-Density Lipoprotein Function,
and Atherosclerosis
n engl j med 364;2 nejm.org january 13, 2011 133

48. Cholesterol Efflux Capacity, High-Density Lipoprotein Function,
and Atherosclerosis
n engl j med 364;2 nejm.org january 13, 2011 133