Personalised Personalised treatment treatment of dyslipidemia of dyslipidemia Professor Hana Rosolova, M.D., Professor Hana Rosolova, M.D., DrSc.,FESC DrSc.,FESC Center of Preventive Cardiology Center of Preventive Cardiology 2nd Medical Department 2nd Medical Department Charles University Prague – Medical Charles University Prague – Medical Faculty in Pilsen Faculty in Pilsen
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Personalised treatment of dyslipidemia Professor Hana Rosolova, M.D., DrSc.,FESC Center of Preventive Cardiology 2nd Medical Department Charles University.
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Personalised treatment Personalised treatment of dyslipidemiaof dyslipidemia
Professor Hana Rosolova, M.D., DrSc.,FESCProfessor Hana Rosolova, M.D., DrSc.,FESCCenter of Preventive CardiologyCenter of Preventive Cardiology
2nd Medical Department 2nd Medical Department
Charles University Prague – Medical Faculty in PilsenCharles University Prague – Medical Faculty in Pilsen
DyslipidemiaDyslipidemia
The most common metabolic disorderThe most common metabolic disorder
Subjects in primary preventionSubjects in primary prevention Subjects ≥ 18 y. + dyslipidemia in the personal Subjects ≥ 18 y. + dyslipidemia in the personal
historyhistory Primary prevention of atherosclerosis Primary prevention of atherosclerosis
in men in men >>40 y., in women 40 y., in women >>50 y. ( 50 y. ( àà 5 y.) 5 y.) Patients with arterial hypertensionPatients with arterial hypertension Subjects with abdominal obesitySubjects with abdominal obesity Serious dyslipidemia in a family memberSerious dyslipidemia in a family member Positive family history of early CVD Positive family history of early CVD
We are treated the patient We are treated the patient
not the lipid levels!not the lipid levels!
We have to assess the global cardiovascular risk and We have to assess the global cardiovascular risk and also individual association between dyslipidemia also individual association between dyslipidemia
and other risk factors and diseasesand other risk factors and diseases
Pharmacotherapy of dyslipidemiasPharmacotherapy of dyslipidemias
A panel aimed at 184 different variants on 34 genes (VeraCode ADME Core Panel, Illumina, San Diego, CA) will be used to identify patients at increased simvastatin-
related myopathyOne or two copies of a variant of SLCO1B1, a gene
involved in the regulation of statin uptake in the liver and associated with increased myopathy risk.
Patients with two copies of the variant have an almost 20-fold increased risk of simvastatin-related myopathy.
Pharmacogenomic Resource for Enhanced Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment Decisions in Care and Treatment (PREDICT)(PREDICT)
Vanderbilt University Medical Center (VUMC)Vanderbilt University Medical Center (VUMC)
Vanderbilt University Medical Center. Vanderbilt doctors to screen patients taking cholesterol-lowering drugs
for harmful genetic variation [press release]. October 28, 2011.
Residual vascular risk Residual vascular risk in patients treated by statinsin patients treated by statins
34,9
24,8
29,6
19,4
0
5
10
15
20
25
30
35
40
DM nonDM
MA
CE
% control
treatment
CTT Collab Group: Lancet 2008;371:117-25
100% 78%
RRR 22%
100% 85%
RRR 15%
Residual Residual riskrisk
Residual Risk Reduction Initiative
International Project
Prof. MUDr. R. Češka, CSc. ČIMS, o.p.s.ČSAT Prof. MUDr. Hana Rosolová, DrSc.
Aterogennic dyslipidemiaAterogennic dyslipidemia
American Diabetes Association. Diabetes Care 2003;26 (Suppl. 1):S83-86
Fenofibrate reduces residual risk Fenofibrate reduces residual risk associatedassociated with high TG and low HDL-C in patients with high TG and low HDL-C in patients with T2DMwith T2DM
0
2
4
6
8
10
12
14
16
18
TG <204 mg/ dL, HDL >34 mg/ dL(n=4,548)
TG ≥204 mg/ dL + HDL-C ≤34 mg/ dL(n=941)
Pro
port
ion w
ith E
vent
Simvastatin
Simvastatin + Fenofibrate
ACCORD LipidACCORD Lipid
4.95% ARR
ACCORD Study Group. N Engl J Med March 14, 2010. Epub.
17.32%
12.37%
10.11% 10.11%
TG TG < < 2.3 mmol/L, HD 2.3 mmol/L, HD >>0.9 mmol/L0.9 mmol/L(n= 4 548)(n= 4 548)
• Atherogennic dyslipidemia - monotherapy or combination with statin (metabolic syndrome, T2DM) residual risk reduction (macro and microangiopathy) • Mixed dyslipidemia (LDL-ch + TG) – statin non-tolerance esp. in the secondary CVD prevention
• Serious hypertriglyceridemia (≥7 mmol/L – prevention of pancreatitis)
Complex effect on mixed Complex effect on mixed dyslipidemia:dyslipidemia: Increase of Increase of HDL-CHDL-C Reduction ofReduction of TG TG about about
20%20% Reduction ofReduction of LDL-C LDL-C
Reduction of LpReduction of Lp((a)a) about about 30 % 30 %
1 – Morgan JM et al. J Cardiovasc Pharmacol Ther 1996;1:195-202.
2 – Goldberg A. et al. Am J Cardiol 2008;85:1100-5.3 – McCormack PL, Keating JM. Drugs 2005;65:2719-40.4 – MORGAN JM et al. Am J Cardiol 2003;91:1432-4.5 – Pan J et al. Diiabetes Obes Metab 2002;4:255-61.
Dyslipidemia are different Dyslipidemia are different Dyslipidemia treatment has to be personalizedDyslipidemia treatment has to be personalized
• type of dyslipidemia, other risk factors and diseases (CV risk)type of dyslipidemia, other risk factors and diseases (CV risk)
• individual disorder of lipid metabolism (manifestation + individual disorder of lipid metabolism (manifestation + genomics)genomics)
• individual sensitivity to the specific drug or to its side effectindividual sensitivity to the specific drug or to its side effect (pharmacogenomics)(pharmacogenomics)