Early atherosclerosis beginning in a young menstruating woman

Only 30 when her symptoms began, our patient has a 25-year history of disease progression.

At 30 years of age, Mrs. A suffered transitory double vision and was found to have a right carotid bruit. Two years later, she underwent carotid endarterectomy. Her father had peripheral vascular disease and also underwent carotid endarterectomy.

A NEW PATIENT

When first seen in our offices, Mrs. A was 33 years old. She was noted to have a stocky body habitus, was substantially overweight at 180 lb, and had a serum cholesterol of 218 mg/dL. During history-taking, she reported smoking a pack of cigarettes daily. Cardiac examination was unremarkable, and BPs in both arms were normal. An ECG was unremarkable.

Laboratory studies (complete blood count, erythrocyte sedimentation rate, cold agglutinins, immunoelectrophoresis, check for monoclonal antibodies, rheumatoid agglutination, antinuclear antibodies, VDRL, electrolytes, and thyroid function) were all within normal limits. A repeat cholesterol was 199, calculated LDL was 100 mg/dL, and HDL was 38 mg/dL.

At age 34, Mrs. A underwent angiography, which revealed bilateral carotid atherosclerosis and atherosclerotic obliteration at the origin of the right vertebral artery. The following year, she received a Dacron graft that ran from the proximal aorta to the right common carotid and subclavian arteries.

When Mrs. A was 36 years old, she complained of lower-extremity claudication after walking two blocks. She said her feet were colder than they had been previously. BPs in her right and left arms were elevated (150/105 and 145/95 mm Hg, respectively). Her cholesterol was 237, and hemoglobin was 17.1 g/dL, with a hematocrit of 48%. Angiography revealed severe aortic bifurcation disease and extensive atherosclerosis of the aortic arch. Dipyridamole-thallium imaging of the heart showed reversible anteroseptal myocardial ischemia. Nevertheless, she underwent angioplasty of the aortic bifurcation without event.

CONTINUING PROBLEMS

At 40 years of age, Mrs. A developed classic angina of effort manifested by retrosternal tightness. Her ECG now showed nonspecific ST-T wave changes. Coronary angiography was performed, and angioplasty and stenting of a 90% right mid-coronary lesion was accomplished. Still, walking in cold weather continued to cause angina. She stopped smoking but remained markedly overweight. Her best cholesterol level was 160 with an HDL of 32 and a calculated LDL of 85. Triglycerides were 214 mg/dL. BPs were well controlled below 140/90 mm Hg.

Repeat coronary angiography when Mrs. A was 43 revealed triple-vessel disease, but all the lesions showed <60% narrowing. No intervention was attempted. The estimated ejection fraction was 55%. There was evidence of moderate diastolic dysfunction.

Because the patient reported continued lower-extremity claudication in spite of palpable dorsalis pedis pulses (“my legs are killing me”), a neurology consultation was obtained. The neurologist diagnosed significant spinal stenosis.

PHARMACOTHERAPY

Mrs. A’s daily medications included simvastatin (Zocor) 40 mg, conjugated estrogens (Premarin) 0.3 mg, atenolol 25 mg, aspirin 81 mg, and vitamin C 500 mg, as well as extended- release diltiazem (Cardizem LA) 240 mg and valsartan/hydrochlorothiazide (Diovan HCT) 180 mg/12.5 mg every morning and atenolol 25 mg at bedtime. She was intolerant to larger dosages of the atenolol, complaining that they caused excessive fatigue.

Now 55 years old (15 years after the stenting of her right coronary artery), Mrs. A continues to work as an usher at sports events, is a remarkably active person, and works outside in all kinds of weather. She complains bitterly of leg pains with walking. Exertion brings on retrosternal tightness. She has remained overweight, complains of a stressful home situation, and has refused repeat coronary angiography.

DISCUSSION

Mrs. A had an unusual condition: accelerated and generalized atherosclerosis beginning in a young menstruating woman. It is true that she had some of the risk factors generally associated with predisposition to atherosclerosis, but for the disease to be grossly manifest in a menstruating female so young places her in a rare category. Unlike many of the reported young women with accelerated atherosclerosis, Mrs. A never took oral contraceptives (OCs), and there never was any evidence of an immune or connective tissue disease. She did stop smoking and took all her medications faithfully, though she continued to be grossly overweight.

The risk factors for accelerated atherosclerosis in young women include hypertension, cigarette smoking, OC use, hyperlipidemia, surgical or premature menopause, underlying inflammatory disease (e.g., lupus erythematosus, rheumatoid arthritis), diabetes mellitus, and family history. Other possible risk factors have included prolonged corticosteroid usage, homocystinemia, thrombocytosis, blood clotting disorders, previous viral infections, hyperinsulinemia and, of course, genetic factors.

Accelerated atherosclerosis in young women has been reported in the literature for some time. In 1974, Oliver wrote a landmark paper titled “Ischaemic heart disease in young women.”1 He subsequently located and studied 150 women under the age of 45 with coronary heart disease. Ten years later, McCready and colleagues reported on 47 patients under age 40 who were seen over the course of 15 years with atherosclerotic vascular disease; there were 12 women in the group.2 The title of the paper is interesting: “Atherosclerosis in the young: a virulent disease.” Most recently, Cole et al reviewed 843 patients seen between 1975 and 1985 who had atherosclerosis prior to age 40. There were 94 women in the group.3

Atherosclerosis in young women, though a relatively rare occurrence, merits close attention and vigorous treatment. In particular, cigarette smoking and OCs should be anathema, and lipid abnormalities and hypertension warrant vigorous treatment. This patient is remarkable in the sense that she has remained an active, productive person at age 55 in spite of her manifest persistent problems and her past problems. It is assumed that the statin therapy, smoking cessation, and control of her hypertension have had salutary effects.

Dr. Miller and Dr. Kaplan are professors of clinical medicine (cardiology) at Feinberg School of Medicine, Northwestern University, in Chicago.

References

1. Oliver MF. Ischaemic heart disease in young women. Br Med J. 1974;4:253-259.

2. McCready RA, Vincent AE, Schwartz RW, et al. Atherosclerosis in the young: a virulent disease. Surgery. 1984;96:863-869.

3. Cole JH, Miller JI 3rd, Sperling LS, Weintraub WS. Long-term follow-up of coronary artery disease presenting in young adults. J Am Coll Cardiol. 2003;41:521-528.

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