cv risk guidelines for argentina: what and how to follow? · who / ish risk prediction chart for...

Argentine Society of LipidsArgentine Lipids Society Guidelines 2016

CV Risk guidelines for Argentina: What and how to follow?

Gerardo Damian Elikir

CV Risk Management 2017 Applying the latest insights to clinical care

Buenos Aires - Argentina April 8, 2017

Argentine Lipids Society Guidelines 2016

• Background

• Methodology

2

Clinical Practice Guidelines on Diagnosis and Treatment of Dyslipidemias in Adults 2016


Authorship On behalf of Committee on Standards and Consensus

3


1.Introduction 1.1.Methodology 1.2.Dyslipidemia and atherosclerosis

1.2.1.Atherosclerosis 1.2.2.Atherogenic lipoproteins: estimation through non-HDL-cholesterol 1.2.3.Low HDL-cholesterol 1.2.4.Triglycerides

2.Studies and diagnosis 2.1.The clinical laboratory in the diagnosis of dyslipidemia

2.1.1.Pre analytic variables 2.1.2.Analytic variables 2.1.3.Indices

2.2.Genetic studies 2.3.Risk stratification

3.Clinical Scenarios 3.1.Menopause 3.2.Secondary dyslipidemias

3.2.1.Hypothyroidism 3.2.2.Cholestasis 3.2.3.Drugs induced dyslipidemias

3.3.Renal disease 3.4.Metabolic syndrome and diabetes mellitus

3.4.1.Metabolic syndrome 3.4.2.Diabetes mellitus

3.5.Dyslipidemia in HIV patients 4.Treatment

4.1.General considerations 4.1.1.How long should lipid-lowering treatment be sustained? 4.1.2.Life-style modifications

4.2.Lipid-lowering drugs intolerance 4.2.1.Relevance of myopathies

4.3.Treatment of hypercholesterolemia 4.3.1.Statins 4.3.2.Ezetimibe 4.3.3.Combined treatment

4.4.Treatment of mixed hyperlipidemia and low HDL-c (“Residual risk”) 4.5.Treatment of severe hypertriglyceridemia

4.5.1.Omega-3 fatty acids 4.5.2.Fibrates 4.5.3.Niacin 4.5.4.Other therapeutic modalities

4.6.Treatment of altered HDL 4.7.Algoritms

5.Conclusions 6.Bibliography

4

Contents


• Lipoprotein metabolism

• Atherosclerosis

• Atherogenic lipoproteins: estimation through non-HDL-cholesterol

• Low HDL-cholesterol

• Pathogenic role for triglycerides

5

1.2.Dyslipidemia and Atherosclerosis


1. The clinical laboratory in the diagnosis of dyslipidemia

2. Genetic studies

3. Clinical assessment of cardiovascular risk

6

2.Studios and diagnosis


• Pre analytic variables

• Analytic variables

• Indices

7

2.1. The clinical laboratory in the diagnosis of dyslipidemia


• There are available several genetic scores for diagnosis and for prognostic

• Genetic studies are not recommended for estimating cardiovascular risk

• Genetic study would be reserved to confirm the clinical diagnosis of familial hypercholesterolemia (HF) in the index case and to facilitate the diagnosis of the relatives (cascade diagnosis)

8

2.2. Genetic studies


2.3. Clinical assessment of cardiovascular risk

9

Intensity of interventions should be proportional to the total cardiovascular risk

WHO / ISH cardiovascular risk prediction chart Recommended by National Ministry of Health

Subregion WHO Member States

Region of the Americas

A Canada, Cuba, United States of America

B

Antigua and Barbuda, Argentina, Bahamas, Barbados, Belize, Brazil, Chile, Colombia, Costa Rica, Dominica, Dominican Republic,

El Salvador, Grenada, Guyana, Honduras, Jamaica, Mexico, Panama, Paraguay Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago, Uruguay, Venezuela

C Bolivia, Ecuador, Guatemala, Haiti, Nicaragua, Peru

WHO Member States by subregion, classified according to mortality stratum (based on World Health Report 2002 )

Prevention of Cardiovascular Disease: guidelines for assessment and management of total cardiovascular risk

WHO / ISH risk prediction chart for AMR B. 10-year risk of fatal or non-fatal cardiovascular event by gender, age, systolic blood pressure,

smoking status and presence or absence of diabetes mellitus

This chart can only be used for countries of the WHO Region of the Americas, sub-region B, in settings where blood cholesterol can be measured

CVD risk may be higher than indicated in the chart in people who are already on antihypertensive therapy, in women who have undergone premature menopause, in people approaching the next age category, and in individuals with any of the following: • obesity (including central obesity); • a sedentary lifestyle; • a family history of premature CHD or stroke in a first degree relative (male < 55 years, female < 65 years); • a raised triglyceride level (> 2.0 mmol/l or 180 mg/dl); • a low HDL cholesterol level (< 1 mmol/l or 40mg/dl in males, < 1.3 mmol/l or 50 mg/dl in females); • raised levels of C-reactive protein, fibrinogen, homocysteine, apolipoprotein B or Lp(a), or fasting glycaemia, or impaired glucose tolerance; • microalbuminuria (increases the 5-year risk of diabetics by about 5%) (38, 83, 85); • those who are not yet diabetic, but have impaired fasting glycemia or impaired glucose tolerance; • a raised pulse rate.

Other risk factors not included in these risk prediction charts such as socioeconomic deprivation and ethnicity should also be taken unto account in addressing and managing a person’s overall CVD risk.


WHO / ISH risk prediction chart for AMR B. 10-year risk of fatal or non-fatal cardiovascular event by gender, age, systolic blood pressure,

smoking status and presence or absence of diabetes mellitus

This chart can only be used for countries of the WHO Region of the Americas, sub-region B, in settings where blood cholesterol CANNOT be measured



2.3. Clinical assessment of cardiovascular risk

13

High risk conditions Disease specific Subclinical atherosclerosis ASCVD

• LDL ≥190 mg/dL (4.9 mmol/L) • Chronic renal disease • Inflammatory diseases (RA,

SLE, PSO) • Cancer survivors • Transplant recipients • Metabolic syndrome

Hypoalfalipoproteinemia • Lp(a) >50 mg/dL (>75 nmol/L)

• Familial Hypercholesterolemia • Diabetes Mellitus

Evidence of atherosclerosis by: • Coronary angiography • Non-invasive imaging • Coronary calcium score • Altered myocardial perfusion • Ankle brachial index

• Angina pectoris • Coronary heart disease • Myocardial infarction • Transient ischaemic attacks • Stroke (from AS origin) • Peripheral vascular disease • Coronary revascularization • Carotid endarterectomy

When can treatment decisions be made without the use of risk prediction

charts?


1. Menopause

2. Secondary dyslipidemias

1. Hypothyroidism

2. Cholestasis

3. Drugs induced dyslipidemias

3. Renal disease

4. Metabolic syndrome and diabetes mellitus

5. Dyslipidemia in HIV patients

14

3. Clinical scenarios


• Estrogens have beneficial effects on the lipid profile

• Menopause is associated with increased cardiovascular risk

• In post menopausal women: • Clinical assessment of CVD risk • Treat concomitant conditions (DYS, HBP, T2DM) • HRT: women 50-59 years-old w/menopause <10

years

15

3.1. Menopause


1. Hypothyroidism • Very frequent cause of dyslipidemia • Treatment is controversial

2. Cholestasis • Treat the cause (autoinmune hepatitis, primary biliar

cirrosis, vanishing bile duct syndrome) • Statins are not contraindicated

3. Drugs induced dyslipidemias • Interactions FK / FD

16

3.2. Secondary dyslipidemias


• High risk condition with specific alterations on lipids • “Conventional” risk factors are very common • “Specific” risk factors can worse the prognosis:

calcium-phosphorus metabolism, nutrition, anemia

• Statins should start before renal replacement therapy

• Adjust doses to renal function (e.g. fibrates)

17

3.3. Chronic kidney disease


• Metabolic syndrome identifies high risk subjects. Independent contribution of each component is controversial

• Abdominal obesity is defined using regional cut points (IDF):

• ♀80cm; ♂ 94cm

• Glycemic control contribute to improve lipoprotein alterations and lipid-lowering treatment is key to reduce high risk on T2DM patients

• Consider absolute risk: • <40 years and recent DM: no statins • > 40 years without risk factors: moderate efficacy statins • > 40 years with risk factors: high efficacy statins

18

3.4. Diabetes, metabolic syndrome and obesity


• Lipid profile varies according stage of HIV infection and treatment

• Similar approach to dyslipidemias than general population. Drug interactions is an issue

• Consider changing on antiretroviral therapy before starting lipid-lowering drugs (if suitable!)

19

3.5. Human immunodeficiency virus infection


• How long should treatment be sustained?

• Therapeutic life-style modifications

20

4. Treatment: general considerations


• Exercise regimented + daily walking

• Smoking cessation

• Healthy dietetic pattern • Increased fresh fruit and vegetables intake • Dietary fiber • Reduction of sugar and refined carbohydrates intake (“Nothing white”)

• Weight reduction

• Functional foods

• Psychosocial factors control (depression, stress, social isolation, rage)

• Controlling additional risk factors (other than DYS): HBP, T2DM

21

STEP 1: therapeutic life-style modifications and risk factors control

<20%

Treatment

Specific treatment

STEP 1: Therapeutic life-style modifications and risk factors control

>20%

<40 years

Therapeutic life-style modifications

>40 years

Moderate efficacy statins

High efficacy statins

High risk conditions

Diabetes mellitus Familiar hypercholesterolemia

>75 years <75 years

Subclinical Ath

STEP 4: Clinical assessment of CVD risk (Risk chart)

STEP 2: Secondary dyslipidemia

STEP 3: Triglycerides >500 mg/dL

ASCVD

c-LDL >50c-LDL >70c-LDL >100

Statins intolerance ? —> See below

Add Ezetimibe / Cholestyramine

Novel drugs

Add Fenofibrate (if high TG / low HDL-c)


Hypertriglyceridemia

23

Severe and refractory: consider genetic forms of hypertriglyceridemia

Inpatient treatment: consider insulin, heparin y aphaeresis

Novel drugs

• Diabetes • Alcohol intake • Apo E phenotype (E2/E2) • Overweight • Drugs / oral contraceptives

Exercise Weight reduction 5-10%

Reduce refined carbohydrates intake Avoid alcohol intake

Hypotriglyceridemic agents

Mild - moderate: mostly secondary

• Primary monogenic LPL deficiency • Secondary monogenic LPL deficiency

(apoC2, apoA5, GPIHBP1, LMF1)


HDL modifications

24

Low HDL-c

Triglycerides >200 mg/dL

See figure 1

Statins

High HDL-c

ASCVD Asymptomatic

Disfunctional HDL

Normal triglyceride levels

?

Control

StatinsFibratesNiacin

Hypoalfalipoproteinemia

See figure 2

Novel drugs (iCETP?)


Management of statin-associated myopathy

25

Asimptomatic

• Not CPK monitoring is required, except in patients with high risk of myopathy* • CPK elevations

• CPK <3 ULN: continue • CPK 3-10 ULN: symptoms assessment and repeat CPK measurement • CPK >10 ULN: stop statin, search causes y predisposing factors (vitD deficiency, electrolyte disturbances, hypothyroidism). Consider risk / benefit ratio

to treatment continuation

Simptomatic

• Tolerable • Search causes y predisposing factors (vitD deficiency, electrolyte disturbances, hypothyroidism) • Dechallenge - re challenge test (to adjudicate causality) • Change statin • Coenzime Q10 supplementation

• Intolerable • Stop statin, down titration, alterne days regime, to máximum tolerable statin doses. Add second cholesterol-lowering drug to attain LDL goal • Confirm statin intolerance (two different statins), if risk is acceptable

Statin Intolerance

• Use of non-statin drugs (mono therapy or combination): • Ezetimibe • Cholestyramine • Niacin • Plant sterols • Red yeast rice (Oryza sativa)

Guideline Strenghts / advantages Weakness Scope

Polish 2016 Evidence-based recommendations Local adapted ESC Guidelines

Local data lackness Dyslipidemia

Argentine Lipids Society 2016

Practice guidelines case-based Integrative approach (goals / fixed dosis)

Spanish

Validation? Implementation issues Dyslipidemia

ESC / EAS 2016 “Traditional” approach (goals-based) Local data lackness CV prevention

Argentine Society of Cardiology 2015

Based on local data Spanish

Just a re-elaboration of foreign guidelines

CV prevention

AHA / ASA 2014Evidence-based recommendations

Simplicity Wide scope of risk factors

Does not adequately consider other dyslipemias other than CT Secondary prevention

AHA / ACC 2013

Evidence-based recommendations Simplicity

Novel (and rational) approach (benefit groups identified)

Hispanic population not included Does not adequately consider other

dyslipemias other than CT Some inusual recommendations

Hypercholesterolemia Secondary prevention

Joint Argentine Societies of

Cardiology 2012

Based on local data Spanish Update needed CV prevention

AHA / ASA 2011Evidence-based recommendations

Simplicity Wide scope of risk factors

Does not adequately consider other dyslipemias other than CT

Stroke prevention

Ministry of Health 2012

(WHO 2003/2007)

Affordability addressed Based on local data

Spanish

Does not adequately consider other dyslipemias other than CT

Update needed

CV prevention (Population approach)

ATPIII 2001Broad dissemination and acceptance

Wide scope of risk factors Introduce Metabolic syndrome

Evidence does not support most recommendations

Dyslipidemia (focus on LDL-c)

We looking forward on September…

14 y 15 de septiembre de 2017 Buenos Aires | Argentina

www.lipidos.org.ar

XIV Reunión Científica Anual I Encuentro internacional SAL - IAS

http://www.lipidos.org.ar


1.1. Methodology: AGREE

29


Paso 2: descartar dislipemias secundarias y dar tratamiento específico

30


Fármacos hipotrigliceridemiantes

31

Dosis y eficacia de los hipotrigliceridemiantes

Grupo Fármaco Dosis diaria Eficacia

Fibratos

Clofibrato (en desuso)GemfibrozilBezafibratoCiprofibratoFenofibrato

Ácido fenofíbrico

500 mg600 - 1200 mg

400 mg100 mg

100 - 350 mg45 - 135 mg

20 - 50%

Ácidos grasos omega-3EPA

DHA + EPA900 - 1800 mg

2 - 4 g25 - 45%

NiacinaLiberación inmediataLiberación extendida

750 - 3000 mg500 - 2000 mg 20 - 40%

EPA: ácido eicosapentaenoico; DHA: ácido docosahexaenoico


• Modificaciones terapéuticas del estilo de vida

• Tratamiento de las condiciones asociadas

• Descartar dislipemias secundarias

• Evaluación del riesgo

• Tratamiento farmacológico

32

Evaluación y tratamiento del paciente con dislipemia

cv risk guidelines for argentina: what and how to follow? · who / ish risk prediction chart for...

Documents