PCC Problem Set

1. PCC Problem Set Jack Blazyk 12/9/04

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

3. 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.

4. Medication None.

5. 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.

6. 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.

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

8. Past Surgical History None.

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

10. 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

11. 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

12. Cardiac Monitor Elevated ST segments in leads II, III, and AVF with ST segment depression in AVL and leads VI-VIII

13. Cardiac Enzymes

14. Cardiac Enzymes

15. Lipid Profile Total Cholesterol 185 mg/dL HDL Cholesterol 52 mg/dL LDL Cholesterol 108 mg/dL Triglycerides 92 mg/dL

16. Emerging Risk Factors • Homocysteine • Lipoprotein(a) • C-reactive protein • CETP isoforms • ApoA-1 isoforms

17. Circulation 102 (2000) 605-610

20. From MedicalBiochemistry, Baynes & Dominiczak, Mosby, 1999.

21. Heart Dis 2001 Sep-Oct;3(5):326-32 • Systemic 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.

25. For a review of inflammatory biomarkers and cardiovascular risk prediction See Blake and Ridker – J. Internal Med. 252 (2002) 283-294

26. 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. 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.

27. 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.

28. 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.

29. Unique Lipoprotein Phenotype and Genotype Associated With Exceptional Longevity See JAMA 290 (2003) 1953 See Barzalai – JAMA 290 (2003) 2030-2040

30. ApoA-I Milano and Coronary Artery Atherosclerosis ApoA-I Milano is a variant of apolipoprotein A-I, the majorprotein component of high-density lipoprotein (HDL) particles.In animal models, infusion of recombinant ApoA-I Milano/phospholipidcomplexes has been shown to rapidly reduce atherosclerotic plaqueburden. Nissen and colleagues conducted a randomizedtrial among patients with acute coronary syndromes and foundthat coronary artery atheroma volume as measured by intravascularultrasound decreased significantly from baseline among thosewho received 5 weekly infusions of recombinant ApoA-I Milano/phospholipidcomplexes. In an editorial,Rader discussesresearch on therapies for atherosclerosis that target HDL.

31. ApoA-I Milano and Coronary Artery Atherosclerosis

32. ApoA-I Milano and Coronary Artery Atherosclerosis See Rader – JAMA 290 (2003) 2322-2324 See Nissen – JAMA 290 (2003) 2292-2300