Dyslipidemia aha acc 2013

DYSLIPEDEMIADr Fahad albedaiwi

Resident family medicine

OBJECTIVES

• Introduction• Epidemiology• Classifications• Diagnosis• Screening• Managment

Introduction

Dyslipidemia is a metabolic disorders characterized by elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein level that contributes to the development of atherosclerosis.

Causes may be primary or secondary.Diagnosis is by measuring plasma levels of total

cholesterol, TGs, and individual lipoproteins. Treatment involves dietary changes, exercise, and lipid-

lowering drugs.

Epidemiology

• As demonstrated in the current study, the prevalence of dyslipidemia among adults in the KSA ranges from 20% to 44%,

CLINICAL CLASSIFICATION OF DYSLIPIDEMIAS

• according to the Fredrickson phenotype (This system does not take into account specific lipoprotein abnormalities)

Etiology

• Primary (genetic) causes and secondary (lifestyle and other)

•1ry {

•Familial hypercholesterolemia•Familial defective apo B-100•PCSK9 gain of function mutations•Polygenic hypercholesterolemia•LPL deficiency•Apo C-II deficiency•Familial hypertriglyceridemia•Familial combined hyperlipidemia•Familial dysbetalipoproteinemia•Primary hypoalphalipoproteinemia (familial or nonfamilial)•Familial apo A/apo C-III deficiency/mutations

•Familial apo A/apo C-III deficiency/mutations•Familial LCAT deficiency•Tangier disease•Familial HDL deficiency•Hepatic lipase deficiency•Cholesteryl ester storage disease and Wolman disease•Sitosterolemia•Cerebrotendinous xanthomatosis

• 2ry:

A sedentary lifestyle Diabetes mellitus Alcohol overuse Chronic kidney disease Primary biliary cirrhosis cholestatic liver diseases

HypothyroidismCigarette smokingObesityDrugs: thiazides, β-blockers, retinoids, highly active antiretroviral agents, cyclosporine, tacrolimus, estrogen and progestins, and glucocorticoids

Diagnosis

• History• Physical examination.• Lipid profile.

Symptoms and Signs

• usually causes no symptoms• paresthesias, dypsnea, and confusion • symptomatic vascular disease: CAD, stroke &

peripheral vascular disease• acute pancreatitis• arcus corneae and tendinous xanthomas• planar or tuberous xanthomas.• a creamy white appearance (lipemia retinalis).

• Serum lipid profile (measured total cholesterol, TG, and HDL cholesterol and calculated LDL cholesterol and VLDL)

screening

• Whom to test ?based on overall cardiovascular (CV) risk .influenced by age, sex, and other risk factors for CV

disease including hypertension, smoking, and family history of premature coronary heart disease (CHD)

2012

management

Statin Benefit groups

• The evidence:– The Expert Panel found extensive and consistent evidence

supporting the use of statins for the prevention of ASCVD in many higher risk primary and all secondary prevention individuals.

– In the RCTs reviewed, initiation of moderateintensity therapy (lowering LDL–C by approximately 30% to <50%), or high-intensity statin therapy (lowering LDL–C by approximately ≥50%), is a critical factor in reducing ASCVD events.

– Statin therapy reduces ASCVD events across the spectrum of baseline LDL–C levels >70 mg/dL.

Statin Benefit groups (Contd.)

• The groups:1. Individuals with clinical ASCVD.2. Individuals with primary elevations of LDL–C >190

mg/dL.3. Individuals with diabetes aged 40 to 75 years with

LDL–C 70 to189 mg/dL and without clinical ASCVD.4. Individuals 40-75 with or without clinical ASCVD or

diabetes with LDL–C 70 to189 mg/dL and estimated 10-year ASCVD risk >7.5%.

Clinical ASCVD

• Clinical ASCVD is defined by the inclusion criteria for the secondary prevention statin RCTs:1. acute coronary syndromes2. history of MI3. stable or unstable angina4. coronary or other arterial revascularization, 5. stroke, TIA, or peripheral arterial disease

presumed to be of atherosclerotic origin).

Other risk factors to consider

• Primary LDL–C ≥160 mg/dL or other evidence of genetic hyperlipidemias

• family history of premature ASCVD with onset <55 years of age in a first degree male relative or <65 years of age in a first degree female relative

• Highsensitivity C-reactive protein >2 mg/L• CAC score ≥300 Agatston score or ≥75 percentile for age,

sex• Ethnicity• ankle-brachial index <0.9

Characteristics predisposing individuals to statin adverse effects

• Multiple or serious comorbidities, including impaired renal or hepatic function.

• History of previous statin intolerance or muscle disorders.

• Unexplained ALT elevations >3 times ULN.• Patient characteristics or concomitant use of

drugs affecting statin metabolism.• >75 years of age.

• Additional characteristics that may modify the decision to use higher statin intensities may include, but are not limited to:– History of hemorrhagic stroke.– Asian ancestry.

Why are we giving statins to everyone!?• The findings support the use of statins to

prevent both nonfatal and fatal ASCVD events.• This can reduce the burden of disability from

nonfatal stroke (for which women are at higher risk than men) and nonfatal CHD events.

• Primary and secondary prevention of ASCVD with statins can reduce rising healthcare costs.

Why are we giving statins to everyone!?• high level of evidence was found that statins reduce total

mortality in individuals with a history of prior ASCVD events (e.g., secondary prevention settings).

• In individuals with no prior history of ASCVD events (e.g., primary prevention setting), there is moderate evidence that statins reduce total mortality in individuals at increased ASCVD risk.

• It should be noted, 2 meta-analyses published after the completion of the Expert Panel’s systematic review provide strong evidence that statins reduce total mortality in primary prevention.

Statin therapy: Moderate and high

Initiating treatment in a patient with ASCVD

Initiating treatment in

a patient with no ASCVD

Monitoring Statin Therapy

Statin intolerance

• It is reasonable to evaluate and treat muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or fatigue, in statin-treated patients according to the following management algorithm: – To avoid unnecessary discontinuation of statins, obtain a history of

prior or current muscle symptoms to establish a baseline before initiating statin therapy.

– If unexplained severe muscle symptoms or fatigue develop during statin therapy, promptly discontinue the statin and address the possibility of rhabdomyolysis by evaluating CK, creatinine, and a urinalysis for myoglobinuria.

Statin intolerance (contd.)• If mild to moderate muscle symptoms develop during

statin therapy: – Discontinue the statin until the symptoms can be evaluated. – Evaluate the patient for other conditions that might increase

the risk for muscle symptoms (e.g., hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases.)

– If muscle symptoms resolve, and if no contraindication exists, give the patient the original or a lower dose of the same statin to establish a causal relationship between the muscle symptoms and statin therapy.

Statin intolerance (contd.)• If a causal relationship exists, discontinue the original statin.

Once muscle symptoms resolve, use a low dose of a different statin.

• Once a low dose of a statin is tolerated, gradually increase the dose as tolerated.

• If, after 2 months without statin treatment, muscle symptoms or elevated CK levels do not resolve completely, consider other causes of muscle symptoms listed above.

• If persistent muscle symptoms are determined to arise from a condition unrelated to statin therapy, or if the predisposing condition has been treated, resume statin therapy at the original dose.

Non statins (Niacin)

Non statins (Bile Acid sequestrants)

Non statins (Chol. Abs. inhibitors)

Non statins (Fibrates)

Non statins (Fibrates)

Non statins (Omega 3 fatty acid)

EPA, eicosapentaenoic acid ; DHA, docosahexanoic acid

Hypertriglyceridemia

• The most clinically relevant complication of hypertriglyceridemia is acute pancreatitis, yet only 10% of cases are a direct consequence of triglyceride levels.

• Because documentation for a specific threshold in triglyceride-induced pancreatitis is lacking, levels associated with increased risk are arbitrarily defined as triglyceride levels 1000 mg/dL

• Although borderline-high and high triglyceride levels (150 to 500 mg/dL) are not associated with pancreatitis, they are correlated with atherogenic RLPs and apo CIII– enriched particles.

• The elevations in triglyceride levels serve as a biomarker for visceral adiposity, IR, DM, and nonalcoholic hepatic steatosis (fatty liver).

RLP = Remenant LipoProtiens, IR = Insulin resistance

Effect of nutrition on TG

Effect of drugs on TG

Take home messages

• The treatment of hyperlipidemia is dependent on the risk it poses on the patient concerning ASVCD.

• Statins are beneficial in both primary and secondary prevention of ASCVD.

• There is not enough evidence to support that hypertriglyceridemia directly poses risk as far as ASCVD.

• Hypertriglyceridemia is a marker for other disease that are directly linked to ASCVD such as visceral adiposity, IR and DM.

Case 1

50 year old white female•Total cholesterol 180

•HDL: 50•SBP: 130

•taking anti-hTN meds•+diabetic•+smoker

•Calculated 10 yr ASCVD: 9.8%

• high intensity statin

Case 248 year old white female

• Total cholesterol 180• HDL: 55• SBP: 130• Not taking anti-hTN meds• +diabetic• Non-smoker• Calculated 10 yr risk ASCVD : 1.8%

• Moderate intensity statin

References

Thankyou