Cardiology W2: Lipid Disorders

USPSTF Lipid Screening

- all adults 40-75yr screen for dyslipidemia

- 21-39yr insufficient evidence to recommend for or against routine lipid screening. Use clinical judgement (I)

- >76yo insufficient evidence to assess the balance of benefits and harm of screening (I)

USPSTF Lipid Screening and Use of Statins for prevention

- adults w/o a hx of CVD use a low-moderate dose statin if age 40-75, have 1+ CVD factors or calculated 10yr risk of CV event of ≥10% (B)

- clinicians selectively offer a statin for the primary prevention of CVD is age 40-75yo, have 1+ CVD factors or calculated 10yr risk of CV event of 7.5%-10% (C)

- 76yo+ to prevent CVD (I)

How does atherosclerosis develop

When excess LDL cholesterol enters the arterial wall, leading to plaque formation and increasing the risk of ASCVD

LDL-C and risk of ASCVD

higher the level of LDL-C, the greater the risk of ASCVD

HDL-C and risk of ASCVD

higher the level of HDL-C, the lower the risk of ASCVD

Lipoproteins

- subfractions of LDL

- elevated levels considered risk factors for ASCVD

- largely genetically determined

What is a Lipoprotein?

A biochemical compound made up of lipids and proteins that allows fats to travel through the bloodstream

Lipoprotein Function

Transport lipids to and from tissues throughout the body

Apoproteins

part of the outer shell of the lipoprotein and help "guide" it

Types of Lipoproteins (5)

- Chylomicrons

- VLDL

- IDL

- LDL

- HDL

Chylomicrons

transport dietary triglycerides

VLDL

- very low density

- takes triglycerides from the liver to the body

LDL

- low density

- delivers cholesterol to cells

HDL

- high density

- removes excess cholesterol from tissues for excretion

HDL Role

- produced in liver and intestine

- reverse cholesterol transport

- transfers cholesterol to other lipoproteins or directly to the liver

Lipoprotein Metabolism

1. liver packages triglycerides into VLDL

2. VLDL delivers triglycerides to muscles/fat for energy or storage

3. VLDL loses triglycerides and becomes LDL

4. LDL delivers cholesterol to body tissue

5. liver removes excess LDL from the blood and eliminated cholesterol in bile

Lipid Panel Componenets

- total cholesterol

- LDL-C

- HDL-C

- triglycerides

- Non-HDL-C

When should you obtain a fasting lipid panel?

- non fasting triglycerides ≥ 400

- suspected genetic dyslipidemia

- FHx of premature ASCVD

- suspected triglyceride metabolism disorder

Fasting Lipid panel: Fasting time

8-12hr prior to draw

What 2 measurements are recommended to measure along side a lipid panel?

- Lipoprotein A (Lp(a))

- Apolipoproetin B (ApoB)

Lp(a) measurement

- once in a lifetime

- identifies a unique inherited risk factor

- mc in African or South Asian ancestry

- Independent of LDL-C and ApoB

- helps identify hidden inherited risk

Elevated Lp(a)

≥ 125 nmol/L

Do you need to fast before drawing a Lp(a)?

No fasting required

elevated Lp(a) risk for

- premature CAD

- stroke

- calcific aortic stenosis

When do you suspect an elevated Lp(a)?

- strong family history of early ASCVD

- recurrent cardiovascular events despite normal LDL-C

What does an Elevated Lp(a) identify?

Identifies patients who may benefit from more aggressive LDL lowering therapy

Is Lp(a) affected by diet and exercise?

No, largely unaffected

ApoB measurement

- monitored overtime to assess therapy response

- measures total atherogenic particle burden

- reflects total number of plaque-forming particles

- better treatment target than LDL-C alone

- helps guide intensity of lipid-lowering therapy

ApoB measure

the number of atherogenic lipoprotein particles and is associated with increased ASCVD risk

elevated ApoB increased risk

- premature CAD

- MI/ischemic stroke

- residual CVD risk despite normal LDL-C

When to suspect elevated ApoB

- elevated triglycerides

- DM/metabolic syndrome/obesity

- familial combined hyperlipidemia

When should you use an ApoB test?

- ASCVD

- CKM syndrome

- DM 2

- elevated triglycerides

- LDL-C/non-HDL tx goals reached but residual risk remains

- characterizing inherited lipid disorders

Hyperlipidemia

elevated LDL, total cholesterol, triglycerides, lipoprotein levels, or low HDL

Hyperlipidemia Etiology

1. primary (familial): polygenic inheritance pattern

2. secondary (acquired): central obesity, saturated fat intake, dietary cholesterol

Hypercholesterolemia

elevated LDL-C

When should you suspect a secondary cause of elevated LDL-C?

When LDL-C is newly elevated, rapidly worsening, or inconsistent with the patient's age or family history

Secondary Causes of Elevated LDL-C (8)

- hypothyroidism (mc)

- DM

- nephrotic syndrome

- CKD

- cholestatic liver disease

- obesity/metabolic syndrome

- diet high in saturated fats

- medications

What tests should you perform to evaluate for secondary causes?

- HbA1c

- urine albumin-to-creatinine ratio

- TSH

- liver and renal function testing

Familial Hypercholesterolemia

- Genetic disorder causing markedly elevated LDL-C from birth

- Significant increased risk of early heart disease and stroke if untreated

Familial Hypercholesterolemia Causes (3)

- defective/absent LDL receptors

- pathogenic variants in ApoB

- increased-function in PCSK9

Familial Hypercholesterolemia Two Types

1. Heterozygous FH (HeFH)

2. Homozygous FH (HoFH)

Which type of Familial Hypercholesterolemia is more common?

HeFH

Familial Hypercholesterolemia Types

Amount of defective genes

- HeFH: 1 defective gene

- HoFH: 2 defective genes

Familial Hypercholesterolemia Types

LDL-C amount

- HeFH: 2-3x normal (≥190)

- HoFH: 4-8x normal (>400-500)

Familial Hypercholesterolemia Types

ASCVD Risk age if untreated

- HeFH: 30s-502

- HoFH: childhood

Familial Hypercholesterolemia HeFH Tx

High intensity static + ezetimibe +/- PCSK9 inhibitor

Familial Hypercholesterolemia HoFH Tx

- multiple agents + LDL apheresis

- occasional liver transplant

Familial Hypercholesterolemia: Lipoprotein Lipase Deficiency

- causes extremely high levels of triglycerides due to disruption of normal fat breakdown

- rare, autosomal recessive mutation of LPL gene

- presents in childhood/adolescence

Familial Hypercholesterolemia: Lipoprotein Lipase Deficiency sx

- recurrent pancreatitis

- abdominal pain

- hepatospenomagaly

- eruptive xanthomas

Familial Hypercholesterolemia: Lipoprotein Lipase Deficiency tx

very low fat diet (no more than 20g/day) for all ages

Familial Hypercholesterolemia

Other Genetics/Lipid Diseases

- familial combined hyperlipidemia

- familial defective apo-100

- familial dysbetalipoproteinemia

familial combined hyperlipidemia

- high total cholesterol, LDL, triglycerides, and low HDL

- hepatic overproduction of LDL and VLDL

familial combined hyperlipidemia clinical manifestations

obesity, premature CVD, xanthelasmas

familial defective apo-100

- autosomal dominant; mutations in the APOB gene

- reduces binding affinity of LDL-C to receptor

- slows clearance of LDL from blood

familial defective apo-100 clinical manifestation

elevated serum cholesterol levels

familial dysbetalipoproteinemia

high total cholesterol and high triglycerides (300-1000)

familial dysbetalipoproteinemia clinical manifestations

premature CHD, xanthomata of palmar creases, tuboeruptive xanthoma

Mixed Hyperlipidemia

elevated triglycerides and LDL-C

Dyslipidemia

imbalance of lipids

When to Refer Lipid related disease

- known genetic lipid disorder

- striking FH of hyperlipidemia or premature ASCVD

- extremely high serum LDL, triglycerides, lipoprotein(a) and extremly low HDL

Clinical Manifestations of Hyperlipidemias (4)

No specific signs but high levels associated with:

- xanthelasma

- xanthomas

- tendinous xanthomas

- eruptive xanthoma

Xanthelasma

localized lipid deposition on the eyelids

Xanthomas

fatty deposits under the surface of the skin

Tendinous xanthomas

may be seen on radiograph

Eruptive Xanthoma

red-yellow papules

Total Cholesteral:

normal female

normal male

- normal female: <200

- normal male < 200

Triglycerides

normal female

normal male

optimal

normal female: 35-135

normal male: 40-160

optimal: <150

LDL

normal female

normal male

optimal

normal female: <130

normal male: <130

optimal: <100

HDL

normal female

normal male

optimal

normal female: >50-55

normal male: >40-45

optimal: >60

Non-HDL

normal female

normal male

optimal

normal female: <159

normal male: <159

optimal: <130

What is the strongest predictor of ASCVD

LDL-C

What medication to target LDL-C?

Statin Therapy

Boarderline/Intermediate CVD risk LDL-C level goal

<100 mg/dL

High CVD risk LDL-C level goal

<70 mg/dL

Very high CVD risk LDL-C level goal

<55 mg/dL

LDL-C <100

- goal for most adults

- continue lifestyle and monitor

LDL-C 130-189

- risk enhancing factor

- consider statin based on PREVENT risk and shared decision making

LDL-C ≥ 190

- severe hypercholesterolemia

- start high intensity statin regardless of calculated PREVENT risk

Clinical ASCVD (prior MI, stroke, PAD)

- secondary prevention

- high intensity statin regardless of LDL level

- goal LDL < 70

Very high risk ASCVD

- highest risk

- goal LDL <55

- add ezetimibe or PCSK9 inhibitor if not at goal

Hypertriglyceridemia

elevated triglycerides

Triglycerides

- carried by VLDL particles

- reflect metabolic dysfunction (insulin resistance, obesity, DM)

Normal Triglycerides

<150

Borderline Triglycerides

150-199

High Triglycerides

200-499

Very High Triglycerides

≥ 500

A patient with very high Triglycerides is at risk for what?

Pancreatitis

Elevated Triglycerides is what?

A marker of atherogenic remnant lipoproteins

What are the advanced risk markers for hyperlipidemia?

Non-HDL and ApoB

Non-HDL

- represents all atherogenic lipoproteins (LDL; VLDL; remnants)

- better predictor than LDL when triglycerides are elevated

When to use Non-HDL-C and ApoB

- high risk patients

- triglycerides ≥200

Risk factors that favor LDL lowering therapy (10)

- FHx of premature ASCVD

- chronic inflammatory disease

- lopoprotein(a)

- CRP ≥ 2

- persistently elevated triglycerides

- CKM syndrome

- elevated atherogenic lipids

- reproductive risk markers

- higher risk ancestry (Sough Asion/Filipino)

- high polygenic risk score

What CRP level supports more intensive lipid lowering therapy?

≥ 2 mg/L on two separate occasions

Coronary Calcium Score (CAC)

- non contrast cardiac CT

- detects calcified coronary plaque

- best test for refining ASCVD risk

When should you use Coronary Calcium Score (CAC)?

- borderline/intermediate risk

- uncertain statin decision

- LDL doesn't match risk

CAC Score: 0

- very low risk

- consider deferring statin

If a patient has a CAC score of 0, when should you still treat with a statin?

If they have DM, smoke, or a strong FHx

CAC Score: 1-99

- mild plaque

- favors statin, especially ≥ 55yrs

CAC Score: ≥100 or 75th percentile

- significant plaque

- statin recommended

1st Line pharmacologic therapy for all lipid disorders

Statins