Cardiovasculaire Geneeskunde.nl

Atherosclerosis in the era of widespread metabolic dysregulation

Slides (presentatie) - Mar. 12, 2009

Nutrition, Obesity, Diabetes and CVD: exploring mechanisms and consequences Atherosclerosis in the era of widespread metabolic dysregulation

Atherosclerosis in the era of widespread metabolic dysregulation Dr JT Tamsma, internist- vasculaire geneeskunde LUMC

Atherosclerosis

Atherosclerosis: changing natural history

Primaire Preventie HVZ

Traditionele RF

Traditionele RF en atherosclerose

Primaire Preventie HVZ

Relevantie “de rest”

Metabolic Syndrome – IDF criteria

MS: cardiovascular mortality

De beperkingen van MS

Associated Factors: pathofysiologie

Het Vervolg

Grundy NRDD 2006

Grundy NRDD 2006

Grundy NRDD 2006

Metabolic dysregulation & atherosclerosis

Visceral obesity

Etiologische momenten MS en atherosclerose

IDF vs NCEP criteria vs mortality

Fat & Insulin Resistance

Visceral Adipose tissue inflammation

Fat and Systemic Inflammation

Athero – inflammation (local & systemic)

Low grade systemic inflammation: CRP

Metabolic dysregulation & atherosclerosis: 2009

Prevalences and associations of these phenotypes

Metabolic dysregulation and Atherosclerosis

Rijswijk: visceral obesity dominates metabolic profile

Rijswijk: visceral obesity dominates metabolic profile

Atherosclerosis?

Does Inflammation change vascular phenotype in Visceral Obese patients

Endpoint: 3T Carotid MRI

10 slides per patient

Quantification wall thickness (VesselMass)

Alizadeh Dehnavi R, Atherosclerosis 2008 200 417

CRP associated will maximal wall thickness in visceral obese patients

Conclusion

Does Inflammation change vascular phenotype in Visceral Obese patients

Alizadeh Dehnavi R, Atherosclerosis 2008 200 417

Causality of individual factors for Multifactorial Diseases

Koch’s postulates

Brown: Cholesterol is causally related to atherosclerosis

Lazar Nature Medicine 2006 12 43

VO & CRP: Hepatic inflammatory response

Metabolic dysregulation & atherosclerosis

VO & Hepatic inflammatory response  atherosclerosis

LIKK mouse model

APOE*3-Leiden.LIKK mouse model

APOE*3-Leiden.LIKK mouse model

Hypothesis

LIKK aggravates atherosclerotic lesion severity

LIKK increases atherosclerotic lesion size

Conclusion

Widespread metabolic dysregulation & atherosclerosis

In Summary: A clinicians view on atherosclerosis

Acknowledgements

Slide 59

South Asian (Hindustani) subjects are at increased risk of CVD and Diabetes

South Asian (Hindustani) subjects are at increased risk of CVD and Diabetes

South Asian (Hindustani) subjects are at increased risk of CVD and Diabetes

Slide 63

Slide 64

EC

Atherosclerosis

Atherosclerosis

Atherosclerosis

Diagnosis Primary Prevention

Cholesterol - statins

Koch’s postulates

Brown: Cholesterol is causally related to atherosclerosis

Change central step in atherogenesis

Change central step in atherogenesis

Statins: regression plaque?

Statins: regression plaque

Statins: Reversal-study

LDL & inflammation lowering: regression

Summary

Remaining Clinical Challenges

Clinical approaches LDL-c

Antisense- A New Drug Class -

ISIS 301012 (Mipomersen) for Cardiovascular Disease

Remaining Clinical Challenges II

HDL-cholesterol important target

HDL-cholesterol important target

HDL-cholesterol important target

HDL-Triglycerides

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