PCC Problem Set

Jack Blazyk12/9/04

Presenting Complaint

“I can’t believe that this is happening,” gasped Prunella.

History of Chief Complaint

Prunella, a 44-year-old Caucasian woman, presents to the ER with severe substernal chest pain that began while she was riding her bike this morning. She continued riding her bike, including a couple of hills, one of which was so steep that she didn’t think she could make it. When her pain persisted and she was unable to find any comfortable position at home, she decided to come to the Emergency Department. She is complaining of severe substernal chest pain that radiates through to her back.

Medication

None.

Habits

Prunella follows a high-carbohydrate diet, with very little red meat. She eats lots of salads, but eats few dark green vegetables. She does not smoke, and only drinks an occasional glass of wine. She exercises regularly, and considers herself to be in great shape.

Social History

Prunella is a computer programmer. She is married and has two daughters, ages 12 and 16. She is an avid gardener (she grows flowers, not vegetables) and always has enjoyed physical activities.

Past Medical History

Prunella was recently diagnosed with Graves’ disease. She was treated at OSU Hospital with 131I.

Past Surgical History

None.

Family Medical History

Unremarkable. Both parents are in good health, and her grandmothers lived to ages 87 and 93.

Physical Examination

General Appearance• Height: 66 inches• Weight: 128 pounds• Alert • Oriented to time, person and place

Vital Signs• Temperature: 98.8°F• Pulse: 110/min• Respirations: 30/min• Blood Pressure: 162/96

Physical Examination

Face• Patient is pale and diaphoretic

Thorax/Breasts• Breathing is labored with use of accessory muscles

of respiration• Patient continues to experience crushing substernal

chest pain

Heart/Lungs• Heart: Regular rhythm, rate 110 bpm, no murmurs• Lungs: Clear to auscultation bilaterally with no

respiratory distress

Cardiac Monitor

Elevated ST segments in leads II, III, and

AVF with ST segment depression in AVL

and leads VI-VIII

Cardiac Enzymes

Cardiac Enzymes

Lipid Profile

Total Cholesterol 185 mg/dL

HDL Cholesterol 52 mg/dL

LDL Cholesterol 108 mg/dL

Triglycerides 92 mg/dL

Emerging Risk Factors

• Homocysteine

• Lipoprotein(a)

• C-reactive protein

• CETP isoforms

• ApoA-1 isoforms

Circulation 102 (2000) 605-610

From Medical Biochemistry, Baynes & Dominiczak, Mosby, 1999.

Heart Dis 2001 Sep-Oct;3(5):326-32Systemic inflammation as a cardiovascular disease risk factor and as a potential target for drug therapy. Kaplan RC, Frishman WH.

Inflammation-related processes play a key role the current etiologic model of atherosclerosis and its acute complications. Recent evidence suggests that blood-based biomarkers that reflect systemic inflammation may contribute to our ability to predict future risk of cardiovascular disease. Global markers of inflammation, such as C-reactive protein and fibrinogen, have been well studied as potential cardiovascular risk factors. A variety of additional markers that reflect various elements of the complex systems governing inflammation, including pro-inflammatory and anti-inflammatory cytokines, mediators of cellular adhesion, and matrix degradation enzymes, are also worthy of study. Although many previous studies have examined the relation of inflammation to myocardial infarction, emerging evidence suggests that other cardiovascular phenotypes such as ischemic stroke and early-stage atherosclerosis may also be related to inflammation. Further elucidating the role of inflammation in cardiovascular disease may lead to the identification of new targets for preventive or therapeutic interventions. In addition, markers of inflammation may be useful as a means to predict or monitor an individual's response to currently available cardiovascular therapies, such as aspirin or HMG coenzyme A reductase inhibitors, that may act via anti-inflammatory mechanisms.

For a review of inflammatory biomarkers and cardiovascular risk prediction

See Blake and Ridker – J. Internal Med. 252 (2002) 283-294

BACKGROUND: Both C-reactive protein and low-density lipoprotein (LDL) cholesterol levels are elevated in persons at risk for cardiovascular events. However, population-based data directly comparing these two biologic markers are not available.

CONCLUSIONS: These data suggest that the C-reactive protein level is a stronger predictor of cardiovascular events than the LDL cholesterol level and that it adds prognostic information to that conveyed by the Framingham risk score.

N Engl J Med. 2002 Nov 14;347(20):1615-7.

Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.

Ridker PM, Rifai N, Rose L, Buring JE, Cook NR.

Researchers Identify A Cholesterol-Related Gene Connected To

Human Aging And Exceptional Longevity

Researchers led by Dr. Nir Barzilai at the Albert Einstein College of

Medicine of Yeshiva University and colleagues have discovered

that a gene mutation helps people live exceptionally long lives and

apparently can be passed from one generation to the next.

The mutation (I 405 V) alters the Cholestryl Ester Transfer Protein

(CETP), an enzyme involved in regulating lipoproteins and their

particle size. CETP affects the size of "good" HDL and "bad" LDL

cholesterol, which are packaged into lipoprotein particles. The

researchers found that the centenarians had significantly larger

HDL and LDL lipoprotein particles than individuals in the control

group. The same finding held true for offspring of the

centenarians but not for control-group members of comparable

ages.

Evidence increasingly indicates that people with small LDL

lipoprotein particles are at increased risk for developing

cardiovascular disease, the leading cause of death in the

United States and the Western world. Dr. Barzilai and his

colleagues believe that large LDL particles may be less apt

than small LDL particles to penetrate artery walls and

promote the development of atherosclerosis, a major

contributor to heart disease and stroke.

The next step for the researchers is to try to develop drugs

that mimic the effects of the CETP gene mutation and,

ultimately, to test them on people who lack the mutation.

"In this way, we can focus on preventing or delaying the

onset of age-related diseases, which can help give people

a better quality of life as they get older," notes Dr. Barzilai.

Unique Lipoprotein Phenotype and Genotype Associated With Exceptional Longevity

See JAMA 290 (2003) 1953

See Barzalai – JAMA 290 (2003) 2030-2040

ApoA-I Milano is a variant of apolipoprotein A-I, the major

protein component of high-density lipoprotein (HDL) particles. In animal models, infusion of recombinant ApoA-I Milano/phospholipid complexes has been shown to rapidly reduce atherosclerotic plaque burden. Nissen and colleagues conducted a randomized trial among patients with acute coronary syndromes and found that coronary artery atheroma volume as measured by intravascular ultrasound decreased significantly from baseline among those who received 5 weekly infusions of recombinant ApoA-I Milano/phospholipid complexes. In an editorial, Rader discusses research on therapies for atherosclerosis that target HDL.

ApoA-I Milano and Coronary Artery Atherosclerosis

ApoA-I Milano and Coronary Artery Atherosclerosis

ApoA-I Milano and Coronary Artery Atherosclerosis

See Rader – JAMA 290 (2003) 2322-2324

See Nissen – JAMA 290 (2003) 2292-2300