DYSLIPIDAEMIA
Figure : Age-standardized deaths due to cardiovascular disease (rate per 100,000), 2004
Kelly et al., 2010. Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. National Academies Press (US);
Burden of CVD in Asia
DM
Gender
Age Reduction of
Diabetes
Hyper- HTN
cholesterol- is the primary
emia
goal
Organ
damage
Smoking
Multiple independent
Integrated identification and management of risk factors
risk factors (silo approach)
contributing to CVD risk
(global approach)
CVD: Cardiovascular disease;
DM: Diabetes mellitus; HTN: Hypertension
Volpe M, et al. J Human Hypertens. 2008;22:154–157.
LDL Cholesterol
is
The Primary Target
in Dyslipidemia Treatment
• Documented CVD
• DM (type 1 or 2) with one or more CV risk factors and/or Patients with clinical ASCVD
Very high risk target organ damage
• Severe CKD
• A calculated SCORE ≥10%.
•Markedly elevated single risk factors Patients with primary elevation of LDL-C of >190 mg/dL
•DM (type 1 or 2) but without CV risk factors or target organ
High risk damage
•Moderate CKD
•SCORE of ≥5% and 10% for 10-year risk of fatal CVD
Patients with diabetes aged 40-75 years with LDL-C of 70-189 mg/dL without
clinical ASCVD
• Subjects are considered to be at moderate risk when
Moderate risk their SCORE is ≥1% and <5% at 10 years
Patients without clinical ASCVD or diabetes with LDL-C of 70-189 mg/dL and
estimated 10-year ASCVD risk of >7.5%
• The low risk category applies to individuals with SCORE
Low risk
<1%.
ACC, American College of Cardiology; AHA, American Heart Association; ASCVD, atherosclerotic cardiovascular disease ; CKD, chronic kidney disease; CV, cardiovascular; CVD,
cardiovascular disease; DM, diabetes mellitus; LDL-C, Low density lipoprotein- cholesterol; SCORE, Systematic Coronary Risk Evaluation Project.
1. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33:1635–1701.
2. Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American
Heart Association Task Force on practice guidelines. 2013. Accessed December 16, 2013.
SCORE Chart: Assessment of Cardiovascular Risk Score
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33:1635–1701
Cardiovascular Risk Reduction: Recommendations of ESC
Guidelines
• Smoking Lifestyle modification
cessation
• Dietary
modification
• Weight Management of comorbid
management
• Physical activity conditions
Lipid-lowering drugs
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33:1635–1701
Lipid-Lowering Medications: Statins have maximum
benefit
Medication Effect on LDL-C Effect on HDL-C Effect on TG Effect on Lp(a)
Nicotinic acid ↓ ↑↑ ↓↓ ↓
Cholesterol absorption ↓↓ ↔ ↔ ↔
inhibitor
CIMT, carotid intima medial thickness; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Lp, Lipo protein; TG, Triglycerides
Jellinger PS , Smith DA, Mehta AE, et al. AACE Guidelines. American association of clinical endocrinologists' guidelines for management of dyslipidemia and prevention of
atherosclerosis. https://www.aace.com/files/lipid-guidelines.pdf. Accessed on December 3, 2013.
2013 ACC/AHA Guideline Recommendations for Statin Therapy
• High-Intensity statin (age ≤75 • High-intensity statin • Moderate-intensity statin • Moderate- to high-intensity
years) statin
• Moderate-intensity statin if • High-intensity statin if
• Moderate-intensity statin if not a candidate for high- estimated 10 year ASCVD risk
>75 years or not a candidate intensity statin ≥7.5%
for high-intensity statin
ASCVD prevention benefit of statin therapy may be less clear in other groups . Consider additional factors influencing ASCVD risk , potential ASCVD
risk benefits and adverse effects, drug-drug interactions, and patient preferences for statin treatment.
Stone NJ, et al. J Am Coll Cardiol. 2013: doi:10.1016/j.jacc.2013.11.002. Available at: http://content.onlinejacc.org/article.aspx?articleid=1770217. Accessed
November 13, 2013.
Intensity of Statin Therapy
High-Intensity Statin Therapy Moderate-Intensity Stain Therapy Low-Intensity Statin Therapy
Lifestyle modification remains a critical component of ASCVD risk reduction, both prior to and in concert with the use of cholesterol lowering drug therapies.
Statins/doses that were not tested in randomized controlled trials (RCTs) reviewed are listed in italics
†Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in IDEAL
‡Initiation of or titration to simvastatin 80 mg not recommended by the FDA due to the increased risk of myopathy, including rhabdomyolysis.
Stone NJ, et al. J Am Coll Cardiol. 2013: doi:10.1016/j.jacc.2013.11.002. Available at: http://content.onlinejacc.org/article.aspx?articleid=1770217. Accessed November 13,
2013.
STATINS MECHANISM OF ACTION
Cholesterol Biosynthesis and the Beneficial and Adverse Downstream Effects of Statin Treatment Beneficial (gray background) and adverse (checkered background) downstream
effects of statin treatment. eNOS = endothelial nitric oxide synthase; HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; LPS = lipopolysaccharide; NAD(P)H = nicotinamide adenine
dinucleotide phosphate; NFκB = nuclear factor kappa B; PI3 = phosphatidylinositol-3; PP = pyrophosphate; tRNA = transfer ribonucleic acid. Important intermediate products in the
mevalonate pathway include the isoprenoids, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate.[1,2] These intermediate products lead to activation of various downstream
intracellular signaling molecules by prenylation of the guanosine triphosphate-binding proteins Rho, Ras, and Rac
http://www.medscape.com/viewarticle/569335_4, http://www.medscape.com/viewarticle/577060_2
PLEIOTROPIC
EFFECTS OF
STATINS
Effects beyond cholesterol
lowering
• improving endothelial function
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694580/
http://content.onlinejacc.org/article.aspx?articleid=1136976
GUIDELINES
ROSUVASTATIN
CLINICAL STUDY
ROSUVASTATIN
PULSAR STUDY
Rosuvastatin 10
mg was more
efficacious than
atorvastatin 20
mg in reducing
LDL-C