SOAP. – Atherosclerosis and Hyperlipidemia

Debbie A. Gunter

Definition

A.Atherosclerosis is a systemic disease characterized by lipid deposition and smooth muscle cell migration and proliferation in the intima of the larger arteries. Atheromatous changes lead to thrombotic stroke, peripheral vascular disease (PVD), atherosclerosis cardiovascular disease (ASCVD), and myocardial infarction (MI).

B.Hyperlipidemia is an elevation in serum lipoproteins and a major risk factor in the development of cardiovascular disease (CVD). The two main lipids in blood are cholesterol and triglyceride. Cholesterol is a relatively insoluble lipid that is necessary for cell membrane formation, steroid and bile salt production, and the development of nerve sheaths. Cholesterol is composed of three clinically significant components: high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein (VLDL). Triglyceride is found in VLDL particles, but its role in atherosclerosis is not clear.

C.The atherosclerotic buildup of lipids, cholesterol, calcium, and cellular debris within the intima of the blood vessels causes plaque formation, vascular remodeling, and acute and chronic obstruction of the lumen of the blood vessels, which in turn decreases blood flow, causing myocardial ischemia and decreased oxygen to other vital organs.

D.In 2013 the American College of Cardiology (ACC) and the American Heart Association (AHA) published guidelines on the assessment of cardiovascular risk, lifestyle management, and treatment of cholesterol to reduce ASCVD risks. A downloadable spreadsheet enabling estimation of 10-year and lifetime risk for ASCVD, and a web-based calculator, is available at my.americanheart.org/cvriskcalculator. These risk tools are used to drive conversations on patient risk factors for ASCVD, potential benefits, negative aspects of risk, and patient preferences regarding initiation of relevant therapies. The assessment of ASCVD risk factors is recommended every 4 to 6 years in adults 20 to 79 years of age who are free from ASCVD. Long-term and lifetime risk information may be used to motivate therapeutic lifestyle changes (TLCs) and to encourage adherence to these changes and pharmacological therapies.

Incidence

A.Atherosclerosis begins in childhood with the development of fatty streaks. The incidence of atherosclerotic diseases increases with age. CVD causes one in four deaths reported each year in the United States. In 2017 heart disease is second only to cancer. The annual direct cost of CVD is estimated at $273 billion and the overall cost of CVD is estimated at $444 billion annually.

B.The leading risk factors for CVD are hypertension (HTN), high cholesterol, and smoking:

1.HTN can increase arterial wall tension, potentially leading to disturbed repair processes and aneurysm formation.

2.Cigarette smoking is associated with an increase in multiple inflammatory markers, including C-reactive protein (CRP), interleukin-6, and tumor necrosis factor.

Pathogenesis

A.Atherosclerosis is in part attributed to the deposition of cholesterol and lipoproteins in arterial smooth muscle cells. Dietary factors, obesity, drugs, and genetic defects in lipoprotein particle metabolism influence lipid and lipoprotein concentrations in blood.

B.Primary hyperlipoproteinemias are either due to singlegene disorders transmitted by simple dominant or recessive mechanisms, or to multifactorial disorders with complicated inheritance patterns.

C.Secondary hyperlipoproteinemias (such as in thyroid disease and diabetes mellitus) occur as part of a constellation of abnormalities in certain metabolic pathways. The association between atherosclerosis, CVD, and hypercholesterolemia is well documented. HDL-C comprises about one-fourth of the total serum cholesterol and acts as a scavenger, removing cholesterol from peripheral tissues and returning it to the liver, which produces a favorable cardioprotective effect. Elevated HDL-C levels are desirable. HDL-C levels more than 60 mg/dL are a negative risk factor for CVD; those below 35 mg/dL are a major risk factor for CVD.

D.LDL-C constitutes 70% of the total serum cholesterol. It is the most atherogenic cholesterol subgroup. LDL-C particles interact with platelets, damaged arterial endothelium, and smooth muscle cells in the process of plaque formation. LDL-C levels of 160 mg/dL or greater are associated with an increased number of cardiac events.

E.VLDL accounts for a small amount of total serum cholesterol and is responsible for carrying triglycerides from the liver. Its role in atherogenesis is uncertain, but an inverse relationship has been observed between VLDL and HDL-C.

Predisposing Factors

A.High-risk factors for CVD events (CVD risk equivalent):

1.Clinical CVD.

2.Symptomatic carotid artery disease.

3.Peripheral arterial disease (PAD).

4.Abdominal aortic aneurysm.

B.Presence of major risk factors (other than LDL-C):

1.Age is the strongest risk factor for the development of CVD:

a.Age older than 45 years for men, older than 55 years for women.

b.Elderly persons experience a higher morbidity and mortality.

2.Cigarette smoking.

3.Low HDL-C level, less than 40 mg/dL.

4.Family history of early CVD: MI or sudden cardiac death younger than 55 years in father or other male first-degree relative, before age 65 in mother or other female first-degree relative.

5.HTN (blood pressure [BP] >140/90 mmHg or on antihypertensive medication).

6.Sedentary lifestyle.

7.Obesity.

8.Metabolic syndrome.

9.Diabetes.

10.Chronic inflammation.

HDL-C of greater than 60 mg/dL is equal to negative risk factor and removes one risk factor from the total count.

Common Complaints

A.There are no complaints or symptoms associated with atherosclerosis and hyperlipidemia. Most lipid abnormalities are detected by routine laboratory testing or as part of a cardiovascular evaluation.

Subjective Data

A.Ask the patient if there is a history of CVD.

B.Discuss his or her past medical history, including predisposing factors for CVD.

C.Have the patient list current medications, including over-the-counter (OTC) and herbal products.

D.Have the patient discuss his or her current diet and exercise routine.

E.Explore the patient’s social habits, including use of alcohol and tobacco.

Physical Examination

A.Check pulse, respirations, BP, height, and weight. Calculate body mass index (BMI) at each subsequent visit. An adult BMI calculator and teen BMI calculator are located at www.cdc.gov/healthyweight/assessing/bmi.

B.Inspect:

1.Funduscopic exam: Examine eyes for premature arcus cornealis, which is a gray opaque line around the cornea caused by lipoid degeneration, and for lipemia retinalis, which is a pale retina with white blood vessels caused by excess serum lipids due to VLDL of more than 2,000 mg/dL or alcoholism.

2.Inspect skin for xanthomas, which appear as red-brown or yellow papules, nodules, or plaque, caused by lipid deposits from high VLDL. Tendinous xanthomas are found on Achilles tendons, patellae, and hands.

3.Inspect joints for Achilles tendonitis and arthritis.

C.Palpate:

1.Palpate abdomen for hepatomegaly or splenomegaly.

2.Palpate neck and thyroid.

D.Auscultate:

1.Perform a complete heart exam.

2.Perform a complete vascular exam.

Diagnostic Tests

A.Laboratory testing:

1.Lipid profile and lipoprotein analysis (see Table 13.1).

2.Complete blood count (CBC).

3.Complete metabolic panel (CMP).

4.Thyroid function studies to exclude disorders of the thyroid.

5.CRP.

6.Hemoglobin A1C (if appropriate).

B.Tests/imaging:

1.Treadmill stress test.

2.Nuclear stress test.

3.Echocardiogram.

4.Ultrasound.

5.CT.

6.Coronary angioplasty.

Differential Diagnoses

Assess patient for the following secondary causes of ASCVD and hyperlipidemia:

A.Atherosclerosis.

B.Hyperlipidemia.

C.Diabetes mellitus.

D.Hypothyroidism.

E.Nephrotic syndrome.

F.Porphyria.

G.Obesity.

H.Obstructive liver disease.

I.Diuretic use.

TABLE 13.1 ATP III Classification of LDL, Total, and HDL Cholesterol (mg/dL)

Determine lipoprotein levels. Obtain complete lipoprotein profile after 9- to 12-hour fast.
LDL Cholesterol-Primary Target of Therapy
<100	Optimal
100–129	Near optimal/above optimal
130–159	Borderline high
160–189	High
>190	Very high
Total Cholesterol
<200	Desirable
200–239	Borderline high
>240	High
HDL Cholesterol
<40	Low
>60	High

ATP, adult treatment panel; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

Plan

A.General interventions:

1.TLCs, including exercise, diet, and weight management, are recommended for all patients.

2.Increased physical activity. The 2013 ACC/AHA guidelines on lifestyle management outline the newest physical activity recommendations advising adults to engage in 40 minutes of aerobic physical activity three to four times a week. The aerobic exercise should involve moderate-to-vigorous intensity to reduce BP, LDL-C, and non-HDL-C. Refer to Chapter 3 for further exercise recommendations from the 2008 Physical Activity Guidelines for Americans for key guidelines for adults 18 to 64 years, older adults, people with chronic medical conditions, and adults with disabilities.

B.Dietary management:

1.Advise the patient that diet modification is the first line of therapy for hyperlipidemia.

2.Explain the cholesterol-lowering diet. Give dietary recommendation sheets. See Appendix B for low-fat/low-cholesterol and dietary approaches to stop hypertension (DASH) diets.

C.Patient teaching:

1.Weight reduction:

a.Explain that weight reduction in patients who are more than 20% over ideal body weight can lower LDL-C and triglyceride levels.

2.Other key dietary recommendations include the following:

a.Reduce intake of saturated fats and trans fats. Aim for 5% to 6% of calories from saturated fat.

b.Increase intake of poly- and monounsaturated fats.

c.Increase intake of soluble fiber (psyllium supplement).

d.Limit intake of alcohol: One drink per day for women and two drinks per day for men.

e.Increase intake of plant stanols and sterols (1 oz of Promise Activ or Benecol spread per day).

f.Increase intake of omega-3 fatty acids from marine sources (salmon or tuna twice a week or supplements).

g.Follow the DASH, Mediterranean, or AHA diet.

h.Lower sodium intake. Consume no more than 2,400 mg/d of sodium. Further reduction to 1,500 mg/d of sodium is associated with greater reduction in BP.

3. See Section III: Patient Teaching Guide Nicotine Dependence.

D.Pharmaceutical therapy: Use clinical judgment when deciding potential benefits, possible side effects, and costs of drug treatment:

1.Drug of choice: HMG-CoA reductase inhibitors (statins):

a.Statins suppress the activity of the key enzyme in cholesterol synthesis in liver; they are highly effective in lowering LDL-C but can cause liver toxicity, myositis, rhabdomyolysis, and low

b.There are four major statin benefit groups:

i.Individuals with the presence of clinical ASCVD, including acute coronary syndromes, a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or PAD.

ii.Individuals with primary elevations of LDL-C greater than 190 mg/dL

iii.Individuals 40 to 75 years of age with diabetes and LDL-C 70 to 189 mg/dL and without clinical ASCVD (refer to Chapter 24 for statin therapy for diabetes).

iv.Individuals without clinical ASCVD or diabetes who are 40 to 75 years of age with an LDL-C 70 to 189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher.

c.ASCVD events are reduced by using the maximum tolerated statin intensity in those groups shown to benefit. The expert panel defines intensity of statin therapy on the basis of the average expected LDL-C response to a specific statin and dose. The intensity levels are high-intensity, moderate-intensity, and lower-intensity statin therapy. Full statin treatment recommendations for primary and secondary prevention as well as the high/moderate/low-intensity statin therapy from the 2013 ACC/AHA guidelines on the treatment of cholesterol are available at http://www.ahajournals.org/doi/10.1161/JAHA.116.004909.

d.Monitor liver function tests (LFTs) before therapy begins, and 4 to 6 weeks after starting drug therapy. Then check at 6- to 12-month intervals or more frequently, if necessary.

e.Discontinue medications if abnormal lab values or adverse symptoms appear.

f.Use caution with the use of statins and other medications. Avoid concomitant drugs such as erythromycin, nicotine, azole antifungals, clofibrate, and gemfibrozil.

g.The use of statins in older adults above age 75 remains controversial. See the Individual Considerations section on geriatrics.

2.Category X drugs:

a.Statins are category X drugs and are contraindicated in pregnancy.

3.Nonstatin drug therapy (see Table 13.2 for the nonstatin drugs that affect cholesterol):

a.Bile acid sequestrants bind bile acids in the gastrointestinal (GI) tract; lower moderately elevated LDL-C by 20%; and may cause constipation, bloating, and poor absorption of other drugs. Bile acid sequestrant therapy is not recommended if triglycerides are greater than 300 mg/dL.

b.Nicotinic acid or niacin: Broad-spectrum lipid regulating agent. Niacin has been documented to exhibit anti-inflammatory properties (reduction of lipoprotein associated phospholipase A2 and CRP). Discuss possibilities of flushing. Niacin is contraindicated with chronic liver disease and severe gout. The niacin-treated subjects in the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health (AIM-HIGH) clinical trial had a trend toward increased stroke incidence.

c.Fibric acid derivatives: Highly effective in lowering triglycerides; lowers VLDL-C, causes modest reduction in LDL-C, and raises HDL-C:

i.The combination of niacin with other lipid-lowering drugs has been shown to reduce progression and promote regression of coronary and carotid atherosclerosis and improve clinical outcomes.

ii.Fibrates may cause GI distress, rash, pain, blurred vision, anemia, and gallstones.

iii.Fibrates may inhibit insulin and oral hypoglycemic absorption, and potentiates oral anticoagulants.

Follow-Up

A.Measure patient’s total cholesterol 4 weeks after initiation of diet and then at 3- to 4-month intervals.

B.If initiating medication therapy, obtain baseline blood work, including fasting lipid profile with LFTs and a CBC. Recheck tests 4 to 6 weeks after starting drug therapy. Then check at 6- to 12-month intervals or more frequently, if necessary.

Consultation/Referral

A.Refer to dietician for nutritional counseling for dietary modifications.

Individual Considerations

A.Geriatrics:

1.The use of statin therapy for primary prevention of ASCVD in those over age 75 remains controversial. The use of the 10-year ASCVD risk calculator almost always exceeds the guideline-recommended treatment threshold in this population. However, there is little evidence that statins provide primary prevention in older adults.

2.The risk for side effects in the use of statins increases with age (myalgias, elevated liver enzymes, cognitive impairment).

3.The American Diabetes Association recommends statins as primary prevention in older adults with diabetes, even in those with no previous CVD who are over age 75.

4.There is compelling evidence supporting the use of statins for secondary prevention in individuals older than 75. Much the same as younger adults, older adults age 75 years and older with clinical ASCVD have been shown to have a reduction in the risk for secondary events when a statin is used.

5.Because of a number of barriers, physical activity participation rates often remain low among many older adults. Older adults who are isolated, frail, have mobility limitations or disabilities, and have fewer resources available may be particularly vulnerable to the effects of inactivity. Chronic pain and arthritis could represent additional barriers to physical activity among populations who are already at high risk of poor health outcomes associated with low levels of physical activity.