Case Report Cardiology 60: 121 128 (1975)
Acute Myocardial Infarction in a Young Female with Familial Hyperbetalipoproteinemia G eorge L ouridas and J osef E delstein 1 Ml. Sinai Hospital of Cleveland, Department of Medicine. Division of Cardiology, Cleveland, Ohio
Key Words. Atherosclerosis • Myocardial infarction • Hyperbetalipoproteinemia • Coronary angiograms Abstract. A young woman, 21 years of age, suffered an acute transmural inferior wall myocardial infarction. EKG changes and serum enzymes accompanied a typical history. Coronary angiography performed 2 months after the acute episode showed complete occlusion of the right coronary artery and some mild disease of the cir cumflex and left anterior descending branches. Family history of type II hyperlipo proteinemia was present and she was known to have high cholesterol since she was 12 years of age.
Introduction
1 We are most grateful to Dr. Howard Simon, Kaiser Foundation Hospital, Cleveland. Ohio, for referring this patient.
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
The occurrence of myocardial infarction in young females is rare [26,28]. Recent studies showed a lower incidence of myocardial infarction in females 30-54 years of age than in men of the same age [1,4, 9, 19] and a predominance of male over female deaths from coronary heart dis ease [24]. Predisposing factors known to increase the likelihood and the magnitude of coronary artery disease in young people are: hypertension, diabetes mellitus and hyperlipidemia [6. 11,13,21]. The significance of oral contraceptives is still controversial [14,16,17,20,27], Myocardial infarctions in young women with intimal fibrous proliferation of the coronary arteries [2] or with normal coronary arteriograms [8] have been
122
I .ouridas/E d h stk in
reported. Patients with familial hypercholesterolemia carry an increased risk of developing coronary heart disease. The genetic background of familial hypercholesterolemia or familial type 11 hyperlipoproteinemia has been well documented [7. 10, 12, 221. The present report refers to a young woman, 21 years of age, with familial type II hyperlipoproteinemia known to be present for the preced ing 10 years, who developed a transmural acute inferior myocardial infarction.
This 21-year-oltl white female was seen for the first time in 1964 when she was 12 years of age. She was admitted for evaluation of elevated blood cholesterol levels. The patient’s mother was noted 2 years previously to have angina pectoris and elevated blood cholesterol levels. Following this, attention was drawn to the fact that the patient had yellowish appearing plaque-like lesions between the thumb and forefinger of each hand for an indeterminate period of time. Physical examination, blood pressure and EKG at that time were normal. There was no corneal arcus present then or now. Serum cholesterol was 620 mg/100 ml while total lipids fluctuated between levels of 900 and 1,900 mg/100 ml. Intravenous glucose tolerance test was normal. She was treated with a low fat diet and cholestyramine but she was not consistent in following her instructions. Her mother, now 58 years of age, has had two myocardial infarctions; one in her early fifties and again 3 years ago. She was treated with the same regime as her daughter. The father, age 58, has no history of coronary disease. A brother, aged 26 and a sister aged 24, are clinically normal but have not been available, inspite of concerted efforts, to be tested for lipid metabolism. Mother and daughter were classified as having familial hyperlipidemia which currently falls into a type II hyperlipoproteinemia. At age 17, the patient was smoking one package of cigarettes per day but has since discontinued this habit. She has been married for 2.5 years and has never been pregnant. She initially took oral contraceptives but discontinued them approximately 1 year ago. On February 1, 1974, she was admitted to the hospital because of severe substernal pressure that awoke her in the middle of the night. The substernal pressure was accompanied by sweating and vomiting. Serial EKGs (fig. I) showed an acute transmural inferior wall myocardial infarction. She evolved uneventfully in the hospital and was discharged in 3 weeks. She has had no previous history of angina before the acute episode of myo cardial infarction. Following her discharge from the hospital, she has remained symptom-free. Seven weeks after her myocardial infarction her serum cholesterol was 345 mg/100 ml and triglycerides 230 mg/100 ml under dietary control and proper doses of clofibrate and cholestyramine. She was seen at Mt. Sinai Hospital in April 1974 for cardiac evaluation. The xanthomas from the fingers had completely disappeared over the years. Her weight
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Clinical History
Acute Myocardial Infarction in a Young Female
123
BO 3 -1 5 -7 4
V,
r
r
r
~
F
"1 Fig.i. 12 lead EKGs obtained 10 weeks after her acute episode showing un questionable evidence of inferior wall myocardial infarction. was 101 lb and blood pressure 120/80 mm Hg. The EKG showed evidence of an old transmural inferior wall myocardial infarction. Physical examination was normal. Left heart catheterization and coronary angiography dig. 2.3) were performed on April 4, 1974. Pressures obtained showed a slight increase in LVEDP at rest. Left ventricular dp/dl at rest was within normal limits. The right coronary artery was totally blocked approximately 1 in from its origin. Collateral circulation filled the distal branches of the right coronary artery which appeared extremely diseased. There was some mild disease in the proximal portions of the circumflex and left anterior descending coronary artery without any significant area of obstruction. The left ventriculogram (fig. 4) showed marked impairment in left ventricular contractility. On April 10, 1974, she was seen having some PVGs originating in the left ventricle and she was placed on quinidine therapy. On March 5, 1975, she was again seen for a routine follow-up visit. She has continued to take her medications in order to control her serum lipid levels and has been following her diet. She was found to be 6 months into her pregnancy and remained totally asymptomatic. Plans are to allow her full-term pregnancy and physiological delivery.
Myocardial infarction is not common in young females. When it occurs, it is usually associated with one or more predisposing factors as hypertension, diabetes mellitus, hyperlipidemia or the use of oral contra ceptives.
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Discussion
124
Louridas/E dels'i EIN
In a study of 9,500 women under the age of 40, in a 10-year period at the Mayo Clinic, 27 had suffered a myocardial infarction with the youngest women being 30 years of age [26]. It was concluded that coronary heart disease did not exist in this age group in the absence of a predisposing factor. The fact that coronary atherosclerosis can occur in early age is sub stantiated by the report of E nos et al. [6], Coronary atherosclerosis from subintimal thickening to complete occlusion of one or more vessels was found in 77% of autopsies of servicemen killed in Korea. The average age was 22 years, the youngest being 18 years old. In another report [23] a 15-year-old boy suffered an acute inferior wall myocardial infarction and died as a consequence of coronary artery dis ease; no mention was made to any predisposing factors. Davia et al. [3] recently reviewed 40 patients under 35 years of age, including four fe males 31-35 years of age, with a history of acute myocardial infarction. Three of the females had hyperlipoproteinemia type II or IV.
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Fig. 2. Selective right coronary artery injection with the patient in a 60° l.AO projection. The catheter is placed at the origin of the main right coronary artery (RCA). There is a total obstruction of the main RCA approximately 1 in front its origin. A well-developed network of collateral circulation is visualized attempting to fill some of the distal branches of the RCA system.
Acute Myocardial Infarction in a Young Female
125
T sakraklides et al. |25] reported a 29-year-old woman with systemic lupus erythematosus who died from an acute myocardial infarction associated with extreme coronary atherosclerosis. Two large studies concerning the incidence of coronary heart disease in young females have recently been described [5, 18]. One of the series [5] consisted of 21 females below 40 years of age. In this study, five pre disposing factors were identified: family history, hypertension, hyper lipidemia, glucose intolerance and cigarette smoking. In the second [18J hypercholesterolemia, hypertension or excessive cigarette smoking were the predisposing factors of coronary heart disease in 145 females under 45 years of age. Our patient is an extremely young female who suffered an acute trans mural myocardial infarction due to coronary atherosclerosis. It is interest ing to note that she was known to have hyperlipidemia since 12 years of age. We could think that if she had been consistent with the proper medical treatment and diet, coronary atherosclerosis and acute myocardial
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Fig. 3. Selective left coronary arteriogram performed with the patient in a 60° I.AO projection showing minimal irregularities in the proximal LAD and circumflex branches.
126
LOURIDAS/EDEI.STEIN
infarction could have been delayed or even avoided. Children known to have hyperlipidemia should be treated promptly with the appropriate regimen if coronary heart disease early in their life is to be avoided [15]. We can only speculate about this matter since the natural history of coronary atherosclerosis is virtually unknown, and the effect of medica tions and diet in vascular lesions in humans with hyperlipidemia is also unknown.
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Fig. 4. Left ventriculogram frames in diastole and systole obtained with the patient in a 30° RAO projection. There is an increased end-systolic volume due to marked impairment in contractility of the inferior wall.
Acute Myocardial Infarction in a Young Female
127
References 1 Bengtsson, C.: Ischemic heart disease in women. A study based on a randomized poptdation sample of women and women with myocardial infarction in Göteborg, Sweden. Acta med. scand., suppl. 549 (1973). 2 Brii.l, I.: Brodeur. M., and O yama. A.: M yocardial infarction in two sisters less than 20 years old. J. Am. med. Ass. 217: 1345 (1971). 3 D avia, J. E.; H allal, J. F.; C heitlin , M. D.; G regoratos, G.; Mc C arty, R., and F oote, W.: Coronary artery disease in young patients. Artériographie and
clinical review of 40 cases aged 35 and under. Am. Heart J. 87: 689 (1974). 4 Dawber, T. R.; M oore, F. E., and M ann, G. V.: Coronary heart disease in the Framingham study. Am. J. publ. Hlth 47: suppl., pp. 4-24 (1957). 5 E ngel, H. J.; P age, H. L., and C ampbell, W. B.: Coronary artery disease in young women. J. Am. med. Ass. 230: 1531-1534 (1974). 6 E nos, W. F.; H olmes, R. H„ and Beyer, J.: Coronary disease among United States soldiers killed in action in Korea. J. Am. med. Ass. 152: 1090 (1953). 7 F redrickson, D. S.; L evy, R. 1., and Lees , R. S.: Fat transport in lipoproteins. An integrated approach to mechanisms and disorders. New Engl. J. Med. 276:
young women with normal coronary arteriograms. Circulation 44: 495 (1971). 9 G undersen, P. R.: Coronary heart disease in Kristiansund, 1959-1961. Incidence, prevalence and mortality (Universitetsforlaget, Oslo 1967). 10 G uravich. i. I..: Familial hypercholesterolemic xanthomatosis. A preliminary report. I. Clinical, electrocardiographic and laboratory considerations. Am. J. Med. 26: 8 (1959). 11 James, T. N.; P ost, H. W., and S mith , F. J.: Myocardial infarction in women. Ann. intern. Med. 43: 153 (1955). 12 J ensen, J.: Blankenborn, D. H., and K ornerup. V.: Coronary disease in familial hypercholesterolemia. Circulation 36: 77 (1967). 13 K annel, W. B.; D owber , T. R.: K agan, A., el «/.: Factors of risk in the develop ment of coronary heart disease. Six years follow-up experience. The Framingham study. Ann. intern. Med. 55: 33 (1961). 14 K ubik, M. M. and Bhowmick , B. K.: Myocardial infarction and oral contra ceptives. Br. Heart J. 35: 1271 (1973). 15 L loyd, J. K.: Hyperlipidaemia in children. Br. Heart J. 37: 105-114 (1975). 16 N aysmith, J. H.: Correspondence: oral contraceptives and coronary thrombosis. Br. med. J. /; 250 (1965). 17 O liver. M. F.: Oral contraceptives and myocardial infarction. Br. med. J. ii: 210 (1970). 18 O liver, M. F.: Ischemic heart disease in young women. Br. med. J. iv: 253-259 (1974). 19 R omo, M.: Factors related to sudden death in acute ischemic heart disease. A community study in Helsinki. Acta med. scand.. suppl. 547 (1972). 20 Scharf, J.; N ahir, A. M.; P eled , B., and A sad, A.: Letters to the editor. Oral contraceptives and myocardial infarction. Lancet ii: 411 (1968).
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
32, 94. 148. 215, 273 (1967). 8 G lancy, D. 1..; M arcus, M. L., and E pstein , S. E.: Myocardial infarction in
128
Louridas/E delstein
21 Segal. B. L.: The distribution and relation of atherosclerosis to coronary heart disease; in L ikoff and M oyer Coronary heart disease, pp. 140-145 (Grune & Stratton, New York 1963). 22 Slack, J.: Risks of ischemic heart disease in familial hyperlipoproteinaemic states. Lancet H: 1380 (1969). 23 Syme, J. and A llan, W. S. A.: Fatal myocardial infarction in a youth of fifteen years. Br. Heart J. 23: 107 (1961). 24 T racy. R. E.: Sex difference in coronary disease. Two opposing views. J. chron. Dis. 19: 1245 (1966). 25 T sakraklides, V. G.; Blieden , L. C„ and E dwards, J. E.: Coronary athero sclerosis and myocardial infarction associated with systemic lupus erythematosus. Am. Heart J. H7: 637 (1974). 26 U nderdahi., L. O. and S mith , H. L.: Coronary artery disease in women under the age of forty. Proc. Staff Meet. Mayo Clin. 22: 479 (1947). 27 W axler, E. B.; K imbiris, D.; V an den Broek , H.; Segal, B. L., and L ikoff , W.: Myocardial infarction and oral contraceptive agents. Am. J. Cardiol. 2S: 96 (1971). 28 Y ater, W. M.; T rum , A. H.; Brown , W. G., cl u l Coronary artery disease in men eighteen to thirty-nine years of age. Am. Heart J. 36: 334-372, 683 722 (1948).
J osef E delstein , M.D., Chief, Division of Cardiology, Mt. Sinai Hospital, 1800 East Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
105th Street, Cleveland, OH 44106 (USA)
Acute Myocardial Infarction in a Young Female with Familial Hyperbetalipoproteinemia G eorge L ouridas and J osef E delstein 1 Ml. Sinai Hospital of Cleveland, Department of Medicine. Division of Cardiology, Cleveland, Ohio
Key Words. Atherosclerosis • Myocardial infarction • Hyperbetalipoproteinemia • Coronary angiograms Abstract. A young woman, 21 years of age, suffered an acute transmural inferior wall myocardial infarction. EKG changes and serum enzymes accompanied a typical history. Coronary angiography performed 2 months after the acute episode showed complete occlusion of the right coronary artery and some mild disease of the cir cumflex and left anterior descending branches. Family history of type II hyperlipo proteinemia was present and she was known to have high cholesterol since she was 12 years of age.
Introduction
1 We are most grateful to Dr. Howard Simon, Kaiser Foundation Hospital, Cleveland. Ohio, for referring this patient.
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
The occurrence of myocardial infarction in young females is rare [26,28]. Recent studies showed a lower incidence of myocardial infarction in females 30-54 years of age than in men of the same age [1,4, 9, 19] and a predominance of male over female deaths from coronary heart dis ease [24]. Predisposing factors known to increase the likelihood and the magnitude of coronary artery disease in young people are: hypertension, diabetes mellitus and hyperlipidemia [6. 11,13,21]. The significance of oral contraceptives is still controversial [14,16,17,20,27], Myocardial infarctions in young women with intimal fibrous proliferation of the coronary arteries [2] or with normal coronary arteriograms [8] have been
122
I .ouridas/E d h stk in
reported. Patients with familial hypercholesterolemia carry an increased risk of developing coronary heart disease. The genetic background of familial hypercholesterolemia or familial type 11 hyperlipoproteinemia has been well documented [7. 10, 12, 221. The present report refers to a young woman, 21 years of age, with familial type II hyperlipoproteinemia known to be present for the preced ing 10 years, who developed a transmural acute inferior myocardial infarction.
This 21-year-oltl white female was seen for the first time in 1964 when she was 12 years of age. She was admitted for evaluation of elevated blood cholesterol levels. The patient’s mother was noted 2 years previously to have angina pectoris and elevated blood cholesterol levels. Following this, attention was drawn to the fact that the patient had yellowish appearing plaque-like lesions between the thumb and forefinger of each hand for an indeterminate period of time. Physical examination, blood pressure and EKG at that time were normal. There was no corneal arcus present then or now. Serum cholesterol was 620 mg/100 ml while total lipids fluctuated between levels of 900 and 1,900 mg/100 ml. Intravenous glucose tolerance test was normal. She was treated with a low fat diet and cholestyramine but she was not consistent in following her instructions. Her mother, now 58 years of age, has had two myocardial infarctions; one in her early fifties and again 3 years ago. She was treated with the same regime as her daughter. The father, age 58, has no history of coronary disease. A brother, aged 26 and a sister aged 24, are clinically normal but have not been available, inspite of concerted efforts, to be tested for lipid metabolism. Mother and daughter were classified as having familial hyperlipidemia which currently falls into a type II hyperlipoproteinemia. At age 17, the patient was smoking one package of cigarettes per day but has since discontinued this habit. She has been married for 2.5 years and has never been pregnant. She initially took oral contraceptives but discontinued them approximately 1 year ago. On February 1, 1974, she was admitted to the hospital because of severe substernal pressure that awoke her in the middle of the night. The substernal pressure was accompanied by sweating and vomiting. Serial EKGs (fig. I) showed an acute transmural inferior wall myocardial infarction. She evolved uneventfully in the hospital and was discharged in 3 weeks. She has had no previous history of angina before the acute episode of myo cardial infarction. Following her discharge from the hospital, she has remained symptom-free. Seven weeks after her myocardial infarction her serum cholesterol was 345 mg/100 ml and triglycerides 230 mg/100 ml under dietary control and proper doses of clofibrate and cholestyramine. She was seen at Mt. Sinai Hospital in April 1974 for cardiac evaluation. The xanthomas from the fingers had completely disappeared over the years. Her weight
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Clinical History
Acute Myocardial Infarction in a Young Female
123
BO 3 -1 5 -7 4
V,
r
r
r
~
F
"1 Fig.i. 12 lead EKGs obtained 10 weeks after her acute episode showing un questionable evidence of inferior wall myocardial infarction. was 101 lb and blood pressure 120/80 mm Hg. The EKG showed evidence of an old transmural inferior wall myocardial infarction. Physical examination was normal. Left heart catheterization and coronary angiography dig. 2.3) were performed on April 4, 1974. Pressures obtained showed a slight increase in LVEDP at rest. Left ventricular dp/dl at rest was within normal limits. The right coronary artery was totally blocked approximately 1 in from its origin. Collateral circulation filled the distal branches of the right coronary artery which appeared extremely diseased. There was some mild disease in the proximal portions of the circumflex and left anterior descending coronary artery without any significant area of obstruction. The left ventriculogram (fig. 4) showed marked impairment in left ventricular contractility. On April 10, 1974, she was seen having some PVGs originating in the left ventricle and she was placed on quinidine therapy. On March 5, 1975, she was again seen for a routine follow-up visit. She has continued to take her medications in order to control her serum lipid levels and has been following her diet. She was found to be 6 months into her pregnancy and remained totally asymptomatic. Plans are to allow her full-term pregnancy and physiological delivery.
Myocardial infarction is not common in young females. When it occurs, it is usually associated with one or more predisposing factors as hypertension, diabetes mellitus, hyperlipidemia or the use of oral contra ceptives.
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Discussion
124
Louridas/E dels'i EIN
In a study of 9,500 women under the age of 40, in a 10-year period at the Mayo Clinic, 27 had suffered a myocardial infarction with the youngest women being 30 years of age [26]. It was concluded that coronary heart disease did not exist in this age group in the absence of a predisposing factor. The fact that coronary atherosclerosis can occur in early age is sub stantiated by the report of E nos et al. [6], Coronary atherosclerosis from subintimal thickening to complete occlusion of one or more vessels was found in 77% of autopsies of servicemen killed in Korea. The average age was 22 years, the youngest being 18 years old. In another report [23] a 15-year-old boy suffered an acute inferior wall myocardial infarction and died as a consequence of coronary artery dis ease; no mention was made to any predisposing factors. Davia et al. [3] recently reviewed 40 patients under 35 years of age, including four fe males 31-35 years of age, with a history of acute myocardial infarction. Three of the females had hyperlipoproteinemia type II or IV.
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Fig. 2. Selective right coronary artery injection with the patient in a 60° l.AO projection. The catheter is placed at the origin of the main right coronary artery (RCA). There is a total obstruction of the main RCA approximately 1 in front its origin. A well-developed network of collateral circulation is visualized attempting to fill some of the distal branches of the RCA system.
Acute Myocardial Infarction in a Young Female
125
T sakraklides et al. |25] reported a 29-year-old woman with systemic lupus erythematosus who died from an acute myocardial infarction associated with extreme coronary atherosclerosis. Two large studies concerning the incidence of coronary heart disease in young females have recently been described [5, 18]. One of the series [5] consisted of 21 females below 40 years of age. In this study, five pre disposing factors were identified: family history, hypertension, hyper lipidemia, glucose intolerance and cigarette smoking. In the second [18J hypercholesterolemia, hypertension or excessive cigarette smoking were the predisposing factors of coronary heart disease in 145 females under 45 years of age. Our patient is an extremely young female who suffered an acute trans mural myocardial infarction due to coronary atherosclerosis. It is interest ing to note that she was known to have hyperlipidemia since 12 years of age. We could think that if she had been consistent with the proper medical treatment and diet, coronary atherosclerosis and acute myocardial
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Fig. 3. Selective left coronary arteriogram performed with the patient in a 60° I.AO projection showing minimal irregularities in the proximal LAD and circumflex branches.
126
LOURIDAS/EDEI.STEIN
infarction could have been delayed or even avoided. Children known to have hyperlipidemia should be treated promptly with the appropriate regimen if coronary heart disease early in their life is to be avoided [15]. We can only speculate about this matter since the natural history of coronary atherosclerosis is virtually unknown, and the effect of medica tions and diet in vascular lesions in humans with hyperlipidemia is also unknown.
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
Fig. 4. Left ventriculogram frames in diastole and systole obtained with the patient in a 30° RAO projection. There is an increased end-systolic volume due to marked impairment in contractility of the inferior wall.
Acute Myocardial Infarction in a Young Female
127
References 1 Bengtsson, C.: Ischemic heart disease in women. A study based on a randomized poptdation sample of women and women with myocardial infarction in Göteborg, Sweden. Acta med. scand., suppl. 549 (1973). 2 Brii.l, I.: Brodeur. M., and O yama. A.: M yocardial infarction in two sisters less than 20 years old. J. Am. med. Ass. 217: 1345 (1971). 3 D avia, J. E.; H allal, J. F.; C heitlin , M. D.; G regoratos, G.; Mc C arty, R., and F oote, W.: Coronary artery disease in young patients. Artériographie and
clinical review of 40 cases aged 35 and under. Am. Heart J. 87: 689 (1974). 4 Dawber, T. R.; M oore, F. E., and M ann, G. V.: Coronary heart disease in the Framingham study. Am. J. publ. Hlth 47: suppl., pp. 4-24 (1957). 5 E ngel, H. J.; P age, H. L., and C ampbell, W. B.: Coronary artery disease in young women. J. Am. med. Ass. 230: 1531-1534 (1974). 6 E nos, W. F.; H olmes, R. H„ and Beyer, J.: Coronary disease among United States soldiers killed in action in Korea. J. Am. med. Ass. 152: 1090 (1953). 7 F redrickson, D. S.; L evy, R. 1., and Lees , R. S.: Fat transport in lipoproteins. An integrated approach to mechanisms and disorders. New Engl. J. Med. 276:
young women with normal coronary arteriograms. Circulation 44: 495 (1971). 9 G undersen, P. R.: Coronary heart disease in Kristiansund, 1959-1961. Incidence, prevalence and mortality (Universitetsforlaget, Oslo 1967). 10 G uravich. i. I..: Familial hypercholesterolemic xanthomatosis. A preliminary report. I. Clinical, electrocardiographic and laboratory considerations. Am. J. Med. 26: 8 (1959). 11 James, T. N.; P ost, H. W., and S mith , F. J.: Myocardial infarction in women. Ann. intern. Med. 43: 153 (1955). 12 J ensen, J.: Blankenborn, D. H., and K ornerup. V.: Coronary disease in familial hypercholesterolemia. Circulation 36: 77 (1967). 13 K annel, W. B.; D owber , T. R.: K agan, A., el «/.: Factors of risk in the develop ment of coronary heart disease. Six years follow-up experience. The Framingham study. Ann. intern. Med. 55: 33 (1961). 14 K ubik, M. M. and Bhowmick , B. K.: Myocardial infarction and oral contra ceptives. Br. Heart J. 35: 1271 (1973). 15 L loyd, J. K.: Hyperlipidaemia in children. Br. Heart J. 37: 105-114 (1975). 16 N aysmith, J. H.: Correspondence: oral contraceptives and coronary thrombosis. Br. med. J. /; 250 (1965). 17 O liver. M. F.: Oral contraceptives and myocardial infarction. Br. med. J. ii: 210 (1970). 18 O liver, M. F.: Ischemic heart disease in young women. Br. med. J. iv: 253-259 (1974). 19 R omo, M.: Factors related to sudden death in acute ischemic heart disease. A community study in Helsinki. Acta med. scand.. suppl. 547 (1972). 20 Scharf, J.; N ahir, A. M.; P eled , B., and A sad, A.: Letters to the editor. Oral contraceptives and myocardial infarction. Lancet ii: 411 (1968).
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
32, 94. 148. 215, 273 (1967). 8 G lancy, D. 1..; M arcus, M. L., and E pstein , S. E.: Myocardial infarction in
128
Louridas/E delstein
21 Segal. B. L.: The distribution and relation of atherosclerosis to coronary heart disease; in L ikoff and M oyer Coronary heart disease, pp. 140-145 (Grune & Stratton, New York 1963). 22 Slack, J.: Risks of ischemic heart disease in familial hyperlipoproteinaemic states. Lancet H: 1380 (1969). 23 Syme, J. and A llan, W. S. A.: Fatal myocardial infarction in a youth of fifteen years. Br. Heart J. 23: 107 (1961). 24 T racy. R. E.: Sex difference in coronary disease. Two opposing views. J. chron. Dis. 19: 1245 (1966). 25 T sakraklides, V. G.; Blieden , L. C„ and E dwards, J. E.: Coronary athero sclerosis and myocardial infarction associated with systemic lupus erythematosus. Am. Heart J. H7: 637 (1974). 26 U nderdahi., L. O. and S mith , H. L.: Coronary artery disease in women under the age of forty. Proc. Staff Meet. Mayo Clin. 22: 479 (1947). 27 W axler, E. B.; K imbiris, D.; V an den Broek , H.; Segal, B. L., and L ikoff , W.: Myocardial infarction and oral contraceptive agents. Am. J. Cardiol. 2S: 96 (1971). 28 Y ater, W. M.; T rum , A. H.; Brown , W. G., cl u l Coronary artery disease in men eighteen to thirty-nine years of age. Am. Heart J. 36: 334-372, 683 722 (1948).
J osef E delstein , M.D., Chief, Division of Cardiology, Mt. Sinai Hospital, 1800 East Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:37:30 PM
105th Street, Cleveland, OH 44106 (USA)
