“This 57-year-old woman had a history that included cholecystectomy at age 37, a hysterectomy at age 55, and elevated TC (>290 mg/dL) that she learned about 2 years ago. Treatment for elevated TC included a statin, which was discontinued because of elevated LFTs, and cholestyramine, which was discontinued because of constipation. At presentation, she claimed that she adhered to an AHA Step I diet, exercised four times a week, drank very little alcohol, and took no medications.

Physical examination was unrevealing: blood pressure, 112/74 mm Hg; height, 5 ft 5 in; and weight, 125 lb. A graded exercise was performed, which revealed a 2-mm ST segment depression in the anterior leads that was present at 1 minute into the recovery period, and was associated with chest discomfort.

Initial laboratory studies (A) were conducted; in addition, subsequent studies were done after treatment with 2,000 mg/day nicotinic acid; folic acid (5 mg/day) and an AHA Step II diet (B), and after the addition of oral CEEs and 250 mg pyridoxine daily (C). The laboratory results are listed below.

“”Women in general may not be as aware as men that coronary disease is a potential threat to their lives.”"

Diagnosed Disorders
On initial examination, the patient was diagnosed as having hypercholesterolemia, which was probably exacerbated by the postmenopausal state. Her LDL-C of 184 mg/dL exceeds the 80th percentile for age-matched women not on hormone therapy. Her low HDL-C of 49 mg/dL is near the 25th percentile. The small, dense LDL trait increases cardiovascular risk threefold. The LDL particle size is particularly small at 254 . Lp(a) is significantly elevated and is in the 90th percentile of 20 mg/dL.

In women with a poor TC:HDL-C ratio and elevated Lp(a), the odds ratio for CHD increases approximately 16-fold. Her ApoE isoform 4/3 indicates one abnormal E-4 allele, which may contribute to some elevation in LDL-C but not to the extent seen in E-4/4 patients. She had a better-than-average response to a low-fat diet in terms of LDL-C reduction. Her fasting homocysteine is slightly elevated, but is significantly elevated following methionine load.

According to the Framingham risk table, this patient’s risk for CHD is 6% over the next 10 years based on an LDL-C of 184 mg/dL and normal levels of other risk factors. These risk factors-elevated LDL-C; relatively low HDL-C, subclass pattern B (threefold increased risk); elevated Lp(a) (threefold increased risk); and homocysteinemia (twofold increased risk)-identifies a patient at very high risk, which warrants noninvasive cardiovascular testing.

“”.approximately three times as many women die from heart attacks each year as compared to the number that die from breast cancer.”"

Prognosis Following Treatment
Following initial treatment with 2,000 mg nicotinic acid and folic acid (5 mg/day), the patient’s LDL-C was lowered but did not achieve the goal of <100 mg/dL in CHD patients. The LDL subclass pattern converted from B to A, reflecting a substantial reduction in small LDL and LDL-C and an increase in HDL-C. Lp(a) was reduced from 84 to 43 mg/dL but remained elevated. Homocysteine appeared to be unaffected by folic acid. The reduction in LDL-C, LDL subclass conversion, and change in Lp(a) were most likely attributable to nicotinic acid, which can also reduce elevated homocysteine levels in many of these patients.

Following the addition of oral CEEs and pyridoxine (250 mg/day), LDL-C was further reduced to 89 mg/dL and Lp(a) to 14 mg/dL. Homocysteine was also reduced. This illustrates the role of multiple interventions in controlling multiple disorders. Diet, nicotinic acid, and estrogen were useful in reducing LDL-C. Nicotinic acid was useful in suppressing the LDL subclass pattern B and increasing HDL-C. Nicotinic acid and estrogen were useful in reducing Lp(a). In addition to folic acid, pyridoxine was necessary to reduce homocysteine.

H. Robert Superko, MD
Director, Cholesterol, Genetics, and Heart Disease Institute
San Mateo, CA
”

bio = I write articles for www.lipidhealth.org, offering continuing medical education (CME) online to healthcare professionals.

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