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

Búsqueda PubMed

“Atherosclerosis AND Lipoprotein”

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+ búsqueda específica en NEJM, Circulation, Diabetes

Estudios básicos y clínicos pero de interés clínico

Total 1269 artículos; Primera selección 84 pdf; Incluidos 44

Estudios básicos y clínicos pero de interés clínico

Estudios en humanos

Selección totalment sesgada por las preferencias del “speaker”

CÉLULAS, MOLÉCULAS, LÍPIDOS Y ARTERIOSCLEROSIS

The Human Plasma Lipidome

N Engl J Med 2011;365:1812-23.

Autophagy Regulates Cholesterol Efflux from Macrophage Foam Cells via Lysosomal Acid Lipase

Cell Metabolism 2011, 13: 655-667

Metabolism: Let them eat fat

Nature:477:166–167; 2011

MicroRNA Modulation of Cholesterol Homeostasis

Arterioscler Thromb Vasc Biol. 2011;31:2378-2382

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.

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.

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)

GUÍAS CLÍNICAS Y CONSENSOS

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

Am J Cardiol 2011;108[suppl]:3B–24B

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

FÁRMACOS, PAUTAS TERAPÉUTICAS Y ENSAYOS CLÍNICOS

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

Safety of Anacetrapib in Patients with or at High Risk for Coronary Heart Disease

N Engl J Med Nov 2010

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

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

dal-VESSEL FMD: Observed change from baseline. No adverse effect of dalcetrapib

2.00

1.75

1.50

1.25

1.00

0.75

Placebo (n=234)Dalcetrapib 600 mg (232)

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23Lüscher et al. ESC 2011.

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Week

Data presented as least squares mean (SE) absolute change from baseline in %FMD at weeks 12 and 36

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AIM-HIGH STUDY

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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 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.

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Related Information•Simvastatin (marketed as Zocor) Information2

•NIH stops clinical trial on combination cholesterol treatment3

NIH Press Release - 5/26/2011

Weighing the Benefits of High-Dose Simvastatin against the Risk of Myopathy

10.1056/nejmp1106689 2 nejm.org

The relationship of vitamin D deficiency to statin myopathy

a b s t r a c tObjective: 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

Atherosclerosis 215 (2011) 23–29

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.

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

ASPECTOS EPIDEMIOLÓGICOS DEL RIESGO CARDIOVASCULAR

Diabetes Mellitus, Fasting Glucose, and Risk of Cause-Specific DeathThe Emerging Risk Factors Collaboration*

N Engl J Med 2011;364:829-41.

Diabetes Mellitus, Fasting Glucose, and Risk of Cause-Specific DeathThe Emerging Risk Factors Collaboration*

N Engl J Med 2011;364:829-41.

Adolescent BMI Trajectory and Risk of Diabetes versus Coronary Disease

N Engl J Med 2011;364:1315-25.

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

Changes in atherosclerotic plaques induced by inhalation of diesel exhaust

Atherosclerosis 216 (2011) 299–306

Traffic Air Pollution and Oxidized LDL

PLoS ONE 6(1): e16200. doi:10.1371/journal.pone.0016200

MARCADORES DE RIESGO CARDIOVASCULAR

Decreased circulating lipoprotein-associated phospholipase A2 levels are associated with coronary plaque regression in patients with ACS

Atherosclerosis xxx (2011) xxx– xxx

Lipoprotein-associated phospholipase A2 testing usefulness among patients with symptomatic intracranial atherosclerotic disease

Andreu Massot et al. Atherosclerosis 218 (2011) 181– 187

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

IMAGEN , FUNCIÓN VASCULAR Y ATEROSCLEROSIS SUBCLÍNICA

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

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

Aortic Pulse Wave Velocity Is Associated With Measures of Subclinical Target Organ Damage

J A C C : C A R D I O V A S C U L A R I M A G I N G , V O L . 4 , N O . 7 , 2 0 1 1

Carotid-Wall Intima–Media Thickness and Cardiovascular Events

n engl j med 365;3 nejm.org july 21, 2011

Evaluation of subclinical atherosclerosis by computed tomographycoronary angiography and its association with risk factors

in familial hypercholesterolemia

Atherosclerosis 213 (2010) 486–491

HDL

Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis

n engl j med 364;2 nejm.org january 13, 2011 133

Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis

n engl j med 364;2 nejm.org january 13, 2011 133