1. Case 1: Elevated LDL-C in a Young Adult

2. Page 2 of 10 *DALY; disability-adjusted life years Routine checkup:  Age:33 years  Sex: male  Status: Except for hypercholesterolaemia when fasting, the patient was in excellent health  Fasting analysis (lipid profile):  TC: 280 mg/dl(7.2 mmol/l)  HDL-C: 60 mg/dl(1.6 mmol/l)  TG: 140 mg/dl(1.6 mmol/l)  Calculated LDL-C: 192 mg/dl(4.9 mmol/l)  Lp(a): 13 mg/dl  Repeated blood sampling confirmed the lipid profile Case 1: Elevated LDL-C in a Young Adult

3. Page 3 of 10 *DALY; disability-adjusted life years Other parameters:  Thyroid, renal and hepatic values: normal  Blood pressure: 110/70 mmHg  There were no clinical signs of atherosclerosis Case 1: Elevated LDL-C in a Young Adult

4. Page 4 of 10 *DALY; disability-adjusted life years Family history:  negative for hypertension, diabetes mellitus and premature CVD  the patient said that his parents and older brother had normal lipid values The patient:  never smoked  was not overweight: 173 cm and 64 kg, or 5 ft 8 in and 140 lb, BMI 21.4 kg/m 2  vigorously played tennis on weekends in addition to jogging 5-6 km (3-4 miles) 2-3 times a week Case 1: Elevated LDL-C in a Young Adult

5. Page 5 of 10 *DALY; disability-adjusted life years Dietary recommendations:  The patient was advised to follow the general cholesterol-lowering diet (NCEP Step I Diet), including:  total fat not exceeding 30% of energy intake  saturated fat not exceeding 10% of energy intake  not more than 300 mg/day dietary cholesterol  Lipid values were checked over a period of several months, and LDL-C stabilised at about 170 mg/dl (4.4 mmol/l) Case 1: Elevated LDL-C in a Young Adult

6. Page 6 of 10 *DALY; disability-adjusted life years What do you recommend to the patient? Begin statin therapy Begin low-dose cholestyramine (8 g/day) in a divided dose Begin ezetimibe 10 mg/day Begin fibrate therapy Adding plant sterols in functional foods to diet Continue with the current programme Case 1: Elevated LDL-C in a Young Adult ABCDEFABCDEF

7. Page 7 of 10 *DALY; disability-adjusted life years Answer: E. Recommend adding plant sterols to functional foods in the diet LDL-C remained elevated (>160 mg/dl, or >4.1 mmol/l) despite exercise and maximum efforts towards dietary control. However, given the patient’s relative youth, otherwise acceptable lipid profile, including high HDL-C and the absence of other risk for CHD, it would be best to defer lipid-lowering pharmacotherapy, which is usually a lifelong therapy. The patient’s LDL-C:HDL-C ratio (2.8) is now at a desirable level (<3) for primary prevention. Still, it would be best to reduce his LDL-C to <130 mg/dl (<3.4 mmol/l). Case 1: Elevated LDL-C in a Young Adult

8. Page 8 of 10 *DALY; disability-adjusted life years Phytosterol characteristics:  Phytosterol-containing foods are a dietary supplement which lowers the mean LDL-C levels by 10-15% in addition to any other treatment previously followed Case 1: Elevated LDL-C in a Young Adult

9. Page 9 of 10 *DALY; disability-adjusted life years Study results from patients similar to this case Effective LDL lowering Case 1: Elevated LDL-C in a Young Adult Placebo 1.8 g Sitostanol2.6 g Sitostanol Figure 1 (Miettinen T et al. N Engl J Med. 1995;333:1308-12). Long-term LDL lowering could be shown.

10. Page 10 of 10 *DALY; disability-adjusted life years Evidence:  Phytosterol therapy is in line with the updated NCEP ATPIII guidelines. The patient’s absolute 10-year CHD risk according to Framingham is below 5%, placing the patient in the low-risk group. The recommended LDL-C treatment goal in this risk category is <160 mg/dl (4.1 mmol/l), and the threshold level for considering drug therapy is ≥190 mg/dl (≥5.0 mmol/l).  Two large studies on asymptomatic persons at risk of coronary heart disease (WOSCOPS, AFCAPS/TexCAPS) have shown that lifestyle changes and lowering LDL-C can substantially reduce the risk of a heart attack (myocardial infarction) in patients with moderately elevated LDL-C. Case 1: Elevated LDL-C in a Young Adult