Preventive Cardiology Case File

Preventive Cardiology Case File

Eugene C. Toy, Md, Michael d . Faulx, Md

Case 25

A 60- year - old-woman is being seen by her primary care provide. This is her second visit, and she has never established care with a physician previously. She did not report any complaints or symptoms during the previous visit, is not taking any medications, and exercises on a regular basis. Her family history is significant for a brother with coronary artery disease requiring in surgical revascularization at age 50 years, and her father died of complications related to congestive heart failure In his mind-70s. The patient does not drink alcohol or use illicit drugs, but she Has smoked two or three cigarettes per day since the age of 21 years. Her vital Signs today include a regular heart rate of 70 bpm and a seated blood pressure of 148/90 mmHg. The remainder of her physical examination is unremarkable, and a comprehensive metabolic panel, including a fasting lipid profile, was obtained prior to the current appointment. The physician reviews these results with the patient, and notes that while her serum electrolytes, blood glucose, live transaminases, and creatinine are all within normal limits, her fasting lipid profile is abnormal, She has a total cholesterol (TC) of 260 mg/dL, a high-density lipoprotein (HDL) value of 42 mg/dL, a triglyceride value of 135 mg/dL, and a calculated low-density lipoprotein (LDL) value of 176 mg/dL.

• What is the most likely diagnosis?
• What is the best next diagnostic step?
• What is the best next step in therapy?

 

Answer to Case 25:

Preventive Cardiology

Summary: This asymptomatic 60-year-old woman has an abnormal lipid profile and is a current smoker, and her risk for experiencing adverse outcomes related to coronary heart disease (CHD) needs to be determined. There is a history of coronary artery disease in her family, and this may also contribute to her risk profile. She is otherwise asymptomatic and exercises regularly, although her in-office blood pressure measurement (148/90 mmHg) is consistent with stage 1 hypertension.

• Most likely diagnosis: Increased risk for development of CHD due to untreated hyperlipidemia, hypertension, and active tobacco use.
• Next diagnostic step: Determine risk profile for development of CHD and major cardiovascular events.
• Next step in therapy: Lifestyle modification to include healthy eating, regular aerobic exercise, smoking cessation, and moderate- or high-intensity statin therapy.

ANALYSIS

Objectives

1. Recognize modifiable and nonmodifiable risk factors for development of coronary heart disease.
2. Be able to determine risk profiles for major adverse cardiovascular events due to CHD.
3. Know when to institute pharmacologic therapies for primary prevention of myocardial infarction and death from cardiovascular causes based on risk profile.

Considerations

This asymptomatic 60-year-old woman has hyperlipidemia and hypertension, and actively smokes, and therefore has three major risk factors for CHD. Given that she is a woman and has pertinent, positive family history for CAD, her CHD risk could be estimated using the Reynolds risk score, but since this model requires the measurement of high-sensitivity C-reactive protein (hs-CRP), her risk can instead be calculated using the Framingham model (see below). According to the Framingham risk prediction tool, her 10-year risk of CHD is 11%, and a combination of therapeutic lifestyle changes and drug therapy with moderate- or high-intensity statin treatment would be indicated. In addition, lifestyle changes and/or drug therapy should be prescribed to reduce her systolic blood pressure and assist with smoking cessation.

Approach To:

The Patient with Increased Risk for CHD

DEFINITIONS

HYPERLIPIDEMIA: An abnormally elevated level of any or all lipids/lipoproteins in the blood.

DYSLIPIDEMIA: An abnormal quantity, either increased or decreased, of lipids in the blood

PRIMARY PREVENTION: Interventions targeted at preventing a disease process from occurring, thereby reducing both the prevalence and the incidence of the disease.

SECONDARY PREVENTION: Interventions targeted at preventing recurrent events from a disease process that has already been diagnosed.

CORONARY HEART DISEASE (CHD): Atherosclerotic disease of the epicardial coronary arteries and their subdivisions, manifested by angina pectoris, myocardial infarction, sudden cardiac death, and ischemic heart failure.

CHD RISK EQU IVALENT: Includes diabetes mellitus, chronic kidney disease, and noncoronary atherosclerotic disease, such as prior stroke, symptomatic carotid artery disease, peripheral vascular disease, and thoracic or abdominal aortic aneurysms.

STATIN THERAPY: Drugs in the HMG-CoA reductase inhibitor family. Statins lower LDL cholesterol and have been shown in numerous large randomized clinical trials to reduce the risk of death and nonfatal cardiovascular events in patients who have or are at risk for developing cardiovascular disease. Their benefit is superior to other lipid-lowering agents, and some of this benefit has been attributed to their “pleotropic” effects, particularly the attenuation of systemic inflammation.

CLINICAL APPROACH

Etiologies

Several modifiable and nonmodifiable risk factors contribute to the development of CHD. Nonmodifiable factors include age, gender, and family history. Hypertension, dyslipidemia, diabetes, smoking, obesity, and kidney disease constitute major modifiable risk factors. It is important to note here that a significant proportion of cases of myocardial infarction (MI) and stroke occur in patients without hyperlipidemia, highlighting the fact that development of atherosclerotic arterial disease is a complex and multifactorial process. More research has, therefore, focused on risk markers for increased inflammation and abnormalities related to thrombosis and hemostasis, such as high-sensitivity C-reactive protein (hs-CRP), blood homocysteine levels, and lipoprotein(a). Risk prediction models that incorporate these more novel risk markers have evolved and are being used more frequently as evidence of their utility grows.

Clinical Presentation

History The clinical history should stratify patients into those with overt or known cardiovascular disease and those with increased risk for the development of atherosclerotic disease. In the former group preventive strategies are focused on secondary prevention and slowing progression of established disease. In addition to risk factor modification, various pharmacologic strategies for secondary prevention are based on the nature and extent of disease and previous cardiovascular events, and include the use of antiplatelet agents, drugs that block the β-adrenergic system, and agents that attenuate the renin-angiotensin-aldosterone axis.

Family and social history are of critical importance in establishing risk profiles, and assessment of the desire and motivation of the patient to attempt tobacco cessation should be undertaken at every visit.

Physical Examination The physical examination may be completely normal, or may reveal evidence of significant coronary and peripheral vascular disease. Auscultation should be carried out to identify bruits over the femoral, renal, and carotid arteries. Signs of left ventricular dysfunction, such as elevated jugular venous pulsations, pulmonary rales, lateral displacement of the point of maximal impulse, and the presence of murmurs and extra heart sounds should be identified.

Treatment

Risk Assessment The first step in the treatment decision process is to establish the individual patient’s risk profile. According to guidelines established by the third panel of the United States National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III or ATP III), the risk of developing CHD should be estimated in those individuals with two or more risk factors for atherosclerotic cardiovascular disease. There are several established risk assessment tools available, and both the Framingham and Reynolds risk calculators are widely available in online formats:

http://cvdrisk.nhlbi.nih.gov/calculator.asp;

http://www.reynoldsriskscore.org.

In the Framingham model, risk estimation is based on age, smoking status, blood pressure, diabetes, total cholesterol, and HDL cholesterol level. The final score estimates the 10-year CHD risk, and stratifies individuals into low (<10%), intermediate (10–20%), or high (>20%) risk. The Reynolds score incorporates all of the risk factors employed by the Framingham model, with the addition of premature family history of CHD (MI in a parent aged <60 years), and high-sensitivity C-reactive protein (hs-CRP). The Reynolds scoring system was developed to improve CHD risk assessment in women, and was shown to reclassify almost half of those women deemed at intermediate risk by the Framingham model into either higher or lower risk categories.

Establishing Goal LDL-C Levels Current recommendations from the National Cholesterol Education Panel (NCEP) advocate the use of risk factor combination and risk estimates based on the models discussed previously to determine the goal

(Data from Stone NJ, Robinson J, Lichtenstein AH, et al. 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 [published online November 12, 2013]. Circulation. doi:10.1161/ 01. cir.0000437738.63853.7a.)

LDL-C level for each individual patient. For the patient with 0 or 1 risk factors, the goal LDL-C level is ≤160 mg/dL. For the patient with known CHD or a CHD risk equivalent, the goal LDL-C is ≤100 mg/dL. For those patients with two or more risk factors, the LDL-C goal is ≤130 mg/dL, unless the estimated 10-year risk (using an established risk calculator) is found to be >20%, in which case the LDL-C goal should again be ≤100 mg/dL .

Quite recently the American College of Cardiology (ACC) and the American Heart Association (AHA) released their 2013 guideline on the treatment of cholesterol to reduce cardiac event rates. Their recommendations are based on reanalysis of previously published data from >24 large primary and secondary prevention trials with the goal of optimizing statin usage in patients at highest risk. Their recommendations represent a bit of a paradigm shift away from targeting specific blood levels of HDL and LDL cholesterol in favor of targeting greater intensity of statin therapy in select populations of patients on the basis of their underlying risk for cardiac events (Table 25-1).

Lifestyle Changes Therapeutic lifestyle changes (dietary modifications, weight loss, regular aerobic exercise) should be a universal recommendation for all patients with risk factors for cardiovascular disease. Patients who opt to begin regular exercise of their own volition have been shown to experience fewer major adverse cardiac events and have lower mortality rates than comparable subjects who do not regularly exercise. Patients should be advised to pursue at least 150 minutes of moderate intensity aerobic exercise or 75 minutes of intense aerobic exercise per week.

Dietary modification should include emphasizing both portion control to reduce excessive caloric intake and dietary composition to avoid excessive intake of saturated fats and simple sugars. Protein intake should consist of nuts and lean meats, and, whenever possible, whole grains should be substituted for simpler carbohydrates. There are numerous heart-healthy diets for patients to choose from that emphasize these fundamental features, such as the dietary approach to stop hypertension (DASH) diet advocated by the National Heart, Lung and Blood Institute (NHLBI) (Table 25-2).

Drug Therapy

The cornerstone agents for the treatment of elevated LDL-C for the primary prevention of CHD are the HMG-CoA reductase inhibitors, also known as statins. Numerous large randomized clinical trials and meta-analyses have demonstrated that statin therapy reduces overall mortality and the rate of cardiovascular events by their LDL-C-lowering effect, and they should be employed in all high-risk individuals, barring intolerance or adverse reactions. The decision to use statins in those patients at low or intermediate risk needs to be individualized, and should involve a discussion with the patient about the anticipated absolute risk reductions with therapy. Interestingly, there is evidence to suggest that statins may reduce the rate of cardiovascular events in relatively healthy individuals with elevated hs-CRP levels despite having LDL-C levels below goal before initiation of therapy, although this concept remains controversial.

CASE CORRELATION

• See also Case 1 (acute coronary syndrome/STEMI), Case 2 (acute coronary syndrome/NSTEMI), Case 4 (chronic coronary artery disease), and Case 5 (peripheral artery disease).

COMPREHENSION QUESTIONS

Match the following intervention (A–E) to the clinical situation (questions 25.1 through 25.4):

A. Initiate statin therapy

B. Recommend a trial of lifestyle modification

C. Use the Reynolds risk calculator to estimate long-term risk of CHD

D. Increase statin dose

25.1 A 45-year-old woman is found to have an elevated total cholesterol, a normal hs-CRP, and an LDL-C of 140 mg/dL. She does not smoke, has stage 1 hypertension, and would like to know whether she will need to initiate statin therapy.

25.2 A 60-year-old woman with insulin-dependent diabetes has recently established care with a new physician. Her most recent LDL-C level was 110 mg/dL. What is the most appropriate management step?

25.3 A 50-year-old woman has an LDL-C of 165 mg/dL and one major risk factor for CHD (stage 1 hypertension). What is the initial management strategy for this individual?

25.4 A 72-year-old man is being seen by his primary care provider. The patient was recently found to have an abdominal aortic aneurysm. His LDL-C is 110 mg/dL on 10 mg simvastatin daily, which he is tolerating without any adverse effects. What is the next best step in management?

ANSWERS

25.1 C. The Reynolds risk score takes gender and hs-CRP level into account, and is a good option in this case for estimating this individual’s risk.

25.2 A. This patient has a CHD equivalent since she is a diabetic. She should be initiated on statin therapy with a goal LDL-C of <100 mg/dL, with an optimal goal of <70 mg/dL.

25.3 B. The goal LDL-C for a patient with 0 or 1 major risk factors is ≤160 mg/dL. If the LDL-C is between 160 and 190 mg/dL, a trial of lifestyle modification is a reasonable initial management strategy.

25.4 D. This patient has a CHD equivalent (abdominal aortic aneurysm). His LDL-C goal is therefore ≤100 mg/dL, and the dose of his statin should be increased.

CLINICAL PEARLS

• Primary and secondary prevention of CHD should always involve therapeutic lifestyle changes and an active dialogue with the patient.
• Patients with two or more major risk factors and a 10-year risk of CHD >20% are treated as though they have a CHD equivalent.
• Smoking is a significant, modifiable risk factor, and the patient’s desire and willingness to quit should be assessed at every patient encounter.
• Cholesterol lowering to reduce cardiac risk should focus on the use of moderate-or high-intensity statin therapy in select groups of patients at high risk for cardiac events.

References

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143. 

Reiner Ž. Statins in the primary prevention of cardiovascular disease. Nat Rev Cardiol. 2013;10:453. 

Ridker PM, Buring JE, Rifai N, et al: Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: The Reynolds risk score. JAMA. 2007;297:611. 

Ridker PM, Danielson E, Fonseca FA, et al: Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195. 

Stone NJ, Robinson J, Lichtenstein AH, et al. 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 [published online November 12, 2013]. Circulation. doi:10.1161/01.cir.0000437738.63853.7a. 

Wilson PW, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 2013;97:1837.

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