Coronary lesion morphology and prognosis in young males with myocardial infarction with or without familial hypercholesterolemia

The present study examined the angiographic characteristics and prognosis of young males under 40 years of age with acute myocardial infarction (AMI) and familial hypercholesterolemia (FH). The study group was divided into an FH group (n=16) and a non-FH group (n=27). Lesion morphology was classified as complex or smooth. Overall 36 patients were followed up for an average of 9.4 years. The frequency of angiographic normal or nonobstructive culprit lesions was significantly higher in the non-FH group (p<0.01). In contrast, the incidence of complex or totally occlusive lesions was higher in the FH group (p<0.01). At 10-year follow-up, survival rates from cardiac death (FH 85% vs non-FH 100%, p=0.06), from AMI (FH 43% vs non-FH 80%, p<0.05), and from any ischemic event at a new lesion (FH 9% vs non-FH 67%, p<0.01) were all reduced in the FH group. These results suggest that the mechanism of AMI in young male patients with FH differs from that in similar aged patients without FH, and that the overall prognosis of these patients is less favorable.     

High and low density lipoprotein cholesterol in myocardial and cerebral infarction.

High density lipoprotein (HDL) and low density lipoprotein (LdL) cholesterol levels were measured in fasting blood samples from 950 healthy subjects and 188 aged patients by a new simple method. The HDL-cholesterol levels and HDL/LDL-cholesterol ratios are significantly higher in females than in males. In the healthy subjects, there are slight decreases in the levels of HDL-cholesterol and HDL/LDL-cholesterol ratio with aging in both sexes. The patients with myocardial infarction had significantly lower HDL-cholesterol levels and HDL/LDL-cholesterol ratios as compared to those of the group without infarction. On the contrary, no differences in total lipoprotein cholesterol levels were observed in the patients with cerebral infarction. The results, obtained in respect of electrocardiographic findings after the isoproterenol stress test, suggest that the HDL-cholesterol levels and HDL/LDL-cholesterol ratios may be related not only to the established myocardial infarction, but also to the presence of coronary atherosclerosis and stenosis.     

Hypercholesterolemic valvulopathy: an aspect of malignant atherosclerosis

Hypercholesterolemia affects not only the coronary artery, but also the aortic root, particularly the aortic valve. Aortic stenosis is critical in the prognosis for most patients with homozygous familial hypercholesterolemia (FH) and some heterozygous FH patients who result in aortic valve replacement (AVR). Histopathological examination of their valves shows lipid deposition, inflammatory cell infiltration and calcification in the aortic cusps. These pathological findings are common in non-FH patients with AVR. In homozygous FH patients, the aortic valves are injured by extreme hypercholesterolemia in a relatively short period of time, whereas in heterozygous FH patients with additional risk factors, the damage to the valves occurs over an intermediate time period. In the non-FH population with several risk factors, an underlying raised serum cholesterol level results in gradual impairment over a number of years. Aortic valvular dysfunction caused by hypercholesterolemia, which we termed hypercholesterolemic valvulopathy is recognized to be a life-threatening complication as the primary clinical characteristic of malignant atherosclerosis.     

Assessment by transesophageal echography of atherosclerosis of the descending thoracic aorta in patients with hypercholesterolemia

This study assesses atheromatous lesions and aortic stiffness of the descending thoracic aorta (DTA) in patients with hyperlipidemia by transesophageal echography (TEE) and investigates the relations between atherosclerotic lesions and aging or serum cholesterol levels in these patients. Subjects included 16 patients with familial hypercholesterolemia (FH), 15 non-FH hyperlipidemic patients (non-FH), and 17 age-matched normal subjects. With use of TEE, the DTA was divided into 4 longitudinal portions of equal length, and the atheromatous lesions of each portion of DTA were scored according to their character and extension by biplane 2-dimensional TEE. The scores of atheromatous lesions from all 4 portions were added together to give the total atheromatous score. Then, after measuring the instantaneous dimensional changes of DTA in a cardiac cycle by M-mode TEE and blood pressure (BP) by a cuff method, we calculated the aortic stiffness parameter beta = ln(systolic BP/diastolic BP)/([Dmaximum - Dminimum]/Dminimum). The beta was significantly higher in FH and non-FH subjects than in normal subjects. In both FH and non-FH subjects, the total atheromatous score correlated with total serum cholesterol levels (r = 0.64 [p <0.01]; r = 0.58 [p <0.05], respectively). There were significant correlations between age and beta in all 3 groups (FH, r = 0.67 [p <0.005]; non-FH, r = 0.53 [p <0.05]; normal subjects, r = 0.49 [p <0.05]), and the slopes of the regression lines of FH and non-FH subjects were much steeper than those of normal subjects. The incidence of atherosis in the DTA was significantly higher in hyperlipidemic patients than in normal subjects, even among the younger members of the hyperlipidemic population with progressive aortic stiffness.     

Effectiveness of mevinolin on plasma lipoprotein concentrations in type II hyperlipoproteinemia

Patients with low-density lipoprotein (LDL) concentrations in the top 10th percentile of the population (type II hyperlipoproteinemia [HLP]) are at increased risk for premature cardiovascular disease; however, the incidence of myocardial infarction and death can be decreased by LDL cholesterol reduction. Mevinolin, an inhibitor of endogenous cholesterol synthesis, has been shown to reduce LDL cholesterol concentrations in a subset of type II patients with heterozygous familial hypercholesterolemia (FH). Using a double-blind, randomized, crossover, placebo-controlled trial, the safety and efficacy of mevinolin were compared in 24 patients with type II HLP with heterozygous FH (n = 6) or without FH type II HLP (n = 18). Compared with placebo treatment, both apolipoprotein B and LDL cholesterol levels were reduced (p less than 0.01) in both FH and non-FH patients by 28 to 34% with mevinolin treatment. In addition, high-density lipoprotein cholesterol levels were significantly increased (p less than 0.001) in both patients with FH (16%) and those with non-FH type II HLP (14%). Patients had no serious or clinically significant adverse effects. Thus, mevinolin is a useful drug for treatment of most patients with elevated plasma LDL cholesterol concentrations.     

Coronary artery ectasia: angiographic, clinical profile and follow-up

Out of 3200 coronary angiograms we reviewed, there were 144 cases of coronary ectasia--an incidence of 4.5 percent. Among these, 122 were associated with atherosclerotic coronary artery disease, i.e. coronary stenosis more than 50 percent (group A) and 22 not associated with coronary artery disease (group B). The patients in groups A and B were compared with age- and sex-matched patients (group C) (n=100) who had coronary artery disease alone without ectasia. The incidence of ectasia was not increased in patients with thoracoabdominal aortic aneurysm i.e. 2/154 (1.8%) or in patients with peripheral occlusive vascular disease i.e. 5/161 (3.1%). Ectasia was typed according to a modified version of the criteria proposed by Markis et al. Type II was the commonest, followed by type I, III and IV. Right coronary artery was the most commonly involved vessel by ectasia followed by left circumflex, left anterior descending artery and left main coronary artery. Diffuse ectasia was seen more frequently in right coronary artery and localised ectasia in left anterior descending artery. Patients in groups A and B had similar epidemiological characteristics, though more patients with ectasia alone (group B) had better left ventricular function and negative stress tests. The patients in group A had a similar incidence of previous myocardial infarction, coronary risk factor profile, treadmill exercise test status and severity of coronary artery disease when compared to group C. On a mean follow-up of 3+/-1.2 years, all the three groups had similar event rates.     

Low density lipoprotein density and composition in hypercholesterolaemic men treated with HMG CoA reductase inhibitors and gemfibrozil

The effects of HMG CoA reductase inhibitor (lovastatin or simvastatin) and gemfibrozil treatment on low density lipoprotein (LDL) density distribution and composition were studied in male patients with heterozygous familial hypercholesterolaemia (FH) (n = 17) or non-familial hypercholesterolaemia (non-FH) (n = 14). In FH patients the HMG CoA reductase inhibitors reduced 'light' LDL particles (density 1.022-1.033 g ml-1) significantly more than 'heavy' LDL (density 1.033-1.059 g ml-1), while a more uniform reduction of 'light' and 'heavy' LDL occurred in non-FH patients. HMG CoA reductase inhibitor treatment increased the apolipoprotein B (apoB) content and decreased the cholesterol/apoB ratio of LDL in FH patients. Gemfibrozil significantly reduced 'heavy' LDL but not the 'light' LDL fraction in both FH and non-FH patients, and the mean cholesteryl ester content of LDL increased, while the Tg content decreased, in both FH and non-FH patients. The results indicate that HMG CoA reductase inhibitor and gemfibrozil treatment have distinctly different effects on the physico-chemical properties of LDL, reflecting their different modes of action on lipoprotein metabolism.     

Cholesterol, atherosclerosis and cerebro-cardiovascular complications in 3,236 elderly autopsy cases

The effect of serum cholesterol on aortic, cerebral, coronary and femoral atherosclerosis as well as on the incidence of cerebral and myocardial infarctions were analyzed in 3,236 consecutive autopsies in the elderly. Serum cholesterol levels declined over the age of 80 in both genders. The cholesterol levels of females were significantly higher than that of males in each age group from the sixties through the nineties. The increase in serum cholesterol was correlated with the progression of coronary atherosclerosis in both genders, but not with cerebral or femoral atherosclerosis. Slight progression of aortic atherosclerosis was observed when serum cholesterol was over 160 mg/dl. Cholesterol induced progression of coronary atherosclerosis was found in cases with hypertension, but not in the normotensive group. In accordance with the progression of coronary atherosclerosis, the incidence of myocardial infarction increased with an elevation of serum cholesterol levels, and this relationship between myocardial infarction and cholesterol levels was found only in patients with hypertension. No correlation was found between the incidence of cerebral infarction and serum cholesterol levels. It was concluded that hypercholesterolemia in the elderly is a risk factor of myocardial infarction in cases with hypertension, but is not a risk factor of cerebral infarction.     

Exercise-induced myocardial ischemia in patients with coronary artery ectasia without obstructive coronary artery disease

BACKGROUND: Aetiology, clinical significance and treatment options for coronary artery ectasia/aneurysm is not clear. OBJECTIVE: We sought to determine whether exercise can induce coronary ischemia in patients with coronary artery ectasia/aneurysm without significant coronary stenosis. METHODS: Coronary artery ectasia was defined as 1.5-2-fold, aneurysm as >2-fold luminal dilatation of the adjacent normal segment. The study patients could have irregularities with ectatic coronaries but they did not have stenotic lesions >50% with visual assessment of two blinded observers. Patients having coronary artery ectasia or aneurysm with prior myocardial infarction, dilated cardiomyopathy, valvular heart disease, bundle branch block, significant ST-T changes were excluded. The control group was formed from a well matched population of 32 patients with normal coronary arteries who have not performed a treadmill test before coronary angiography. The study group underwent a symptom limited treadmill test if they did not have one before coronary angiogram, all control patients underwent treadmill test. RESULTS: Thirty-three patients with coronary artery ectasia/aneurysm (ranging from one to three vessels) but without significant stenosis were derived from 4470 cardiac catheterization procedures between January 1998 and July 2000. In the study group, 17 of the patients had positive treadmill tests with respect to five patients in the control group (P = 0.004). In subgroup analysis, diffuse ectasia/aneurysm (involving 2-3 vessels) was found to be strongly related with ischemia (P = 0.005) with respect to local disease. CONCLUSION: Coronary artery ectasia/aneurysm may lead to exercise induced ischemia, especially in the diffuse form.     

Reduced apolipoprotein E-rich high-density lipoprotein level at birth is restored to the normal range in patients with familial hypercholesterolemia in the first year of life

BACKGROUND: High-density lipoprotein (HDL) consists of apolipoprotein E (apoE)-rich and apoE-poor HDL particles. ApoE-rich HDL level is high at birth but decreases after birth with reciprocal elevation in low-density lipoprotein (LDL)-cholesterol. OBJECTIVES: The objective of the study was to clarify whether apoE-rich HDL decreases after birth in children with familial hypercholesterolemia (FH), a disorder caused by impaired LDL clearance. METHODS: We measured apoE-rich HDL-cholesterol and LDL-cholesterol during the first year of life in 10 FH children (one homozygote and nine heterozygotes), 12 non-FH siblings, and 75 healthy controls. RESULTS: At birth, apoE-rich HDL-cholesterol was undetectable in a homozygous FH child and lower in heterozygous FH children than non-FH siblings and controls (4+/-2 vs. 12+/-4 and 11+/-4 mg/dl, P<0.001). At 3-4 months, apoE-rich HDL-cholesterol increased in homozygous and heterozygous FH children and decreased in non-FH siblings and controls. At 12 months, apoE-rich HDL-cholesterol levels were similar among these four groups (6-7 mg/dl). In contrast, LDL-cholesterol concentration was always twice as high in heterozygous FH children as non-FH siblings and controls (at birth, 50+/-15 vs. 25+/-7 and 25+/-5 mg/dl, P<0.001; at 3-4 months of age, 159+/-29 vs. 71+/-16 and 73+/-15 mg/dl, P<0.001; at 12 months of age, 156+/-29 vs. 75+/-18 and 76+/-17 mg/dl, P<0.001). CONCLUSION: ApoE-rich HDL level is low at birth in FH children and increases to the normal level in the first year of life, opposite to the change in normal children.     

Coronary risk factors used to predict coronary artery disease by logistic regression analysis.

Risk factor analysis in coronary artery disease was conducted in 303 patients who underwent coronary arteriography to identify associations between personal characteristics and the prevalence of coronary heart disease. Age, sex, obesity, smoking, alcohol intake, hypertension, diabetes mellitus, serum uric acid, total cholesterol, LDL- and HDL-cholesterol, triglyceride, and atherogenic indices were statistically analyzed. All 13 variables were first compared between patients with positive and negative ergonovine tests. Only total cholesterol was significantly different, while significant differences in age, sex, history of diabetes, total cholesterol, LDL- and HDL-cholesterol, triglyceride and atherosclerotic indices were observed between patients with and without organic coronary artery stenosis. A multivariate analysis was performed, and the resulting equation was tested using the remaining patients. Logistic analysis of all 13 variables identified 5 (age, sex, diabetes mellitus, LDL- and HDL-cholesterol) which accounted for the differences between patients with and without significant coronary artery disease and that were validated in the test group. The sensitivity for prediction of coronary artery disease was 75.8%, specificity 68.5%, and predictive accuracy 71.5% in the test group. Thus, risk factor analysis appears to be very valuable in screening subjects with high-risk organic coronary stenosis and in optimizing the preventive and therapeutic modalities, but not in predicting vasospastic subjects.     

Extracoronary atherosclerosis in familial hypercholesterolemia

Sixty-two patients (31 males, 31 females) with familial hypercholesterolemia (FH) underwent a vascular examination by Doppler ultrasound. The ankle/arm systolic pressure index was determined, and serum lipoproteins were analyzed. Eight of 124 legs examined (6.5%) showed an ankle/arm pressure index less than 0.95, suggesting flow reducing stenosis. Common carotid, internal carotid, and iliac arteries were evaluated by echo Doppler examination with spectral analysis. Forty-five of the 372 arteries examined (12.1%) had detectable abnormalities at echo Doppler examination. Iliac and internal carotid artery lesions were significantly (P less than 0.01) more frequent among FH patients than in a control group (30 men, 20 women) comparable for sex and age. The mean age of the patients with heterozygous FH and detectable arterial lesions was 45.3 years and that of those without lesions 30.7 years (P less than 0.05). When 14 patients with heterozygous FH and arterial lesions were compared to another 14 without lesions and matched for age and gender, it was found that patients with lesions had on average lower concentrations of HDL-cholesterol, and that 10 of 14 cases were actual smokers.     

The natural history of aneurysmal coronary artery disease.

OBJECTIVE: To assess the contribution of coronary artery ectasia, either isolated or in association with obstructive coronary artery disease, to morbidity and mortality from ischaemic heart disease. DESIGN: A retrospective study of patients undergoing coronary arteriography at a tertiary cardiac centre. PATIENTS AND METHODS: The epidemiological, clinical, arteriographic, and follow up characteristics of three groups of patients were examined: group A, 172 patients with coronary artery ectasia and coexisting significant coronary artery disease; group B, 31 patients with coronary artery ectasia only; group C, 165 patients with significant coronary artery disease but without ectasia, matched for sex and age with group A. RESULTS: Group A patients had a similar incidence of a previous myocardial infarction to group C patients (61.6% v 64.2%), exercise performance, severity of obstructive lesions (CASS score 2.19 v 2.14), and similar distribution of diseased vessels. At follow up of approximately two years they experienced a similar incidence of unstable angina (7.5% v 4.4%) and myocardial infarction plus cardiac death (4.9% v 6.1%). They underwent bypass surgery with similar frequency (39% v 42%) but there was a lower frequency of percutaneous transluminal coronary angioplasty (5.8% v 17%, P < 0.01). Patients with pure coronary ectasia (group B) had a lower incidence of a previous myocardial infarction (38.7%, 12/31, P < 0.05) than the two other groups. The infarct in all cases was related to an ectatic artery. Their exercise performance and ejection fraction (9 (SD 3) minutes and 56.5(9)%) were higher (P < 0.01) than group A (5 (2) minutes, 48.3(10)%) and group C (5.3 (2) minutes, 49.3(10)%). Group B had no myocardial infarctions, cardiac death, surgery, or intervention at follow up; 4.4% (5/115) developed unstable angina. The incidence of angina at study entry was similar in all three groups (38.7-49.7%). CONCLUSIONS: Coronary artery ectasia does not confer added risk in patients with coexisting obstructive coronary artery disease. Although there is a measurable incidence of previous myocardial infarction, patients with pure ectasia have a good prognosis. The wisdom of giving oral anticoagulants to such patients is questioned.     

Ultrasonography in the detection of Achilles tendon xanthomata in heterozygous familial hypercholesterolemia.

We have examined the usefulness of ultrasound (US) in the detection of Achilles tendon (AT) xanthomata in heterozygous familial hypercholesterolemia. Our study is based on 30 adult subjects with heterozygous familial hypercholesterolemia (FH) (16 men, 14 women), 27 subjects with other non-familial forms of severe hypercholesterolemia (non-FH) with serum total cholesterol levels > or = 8 mmol/l (13 men and 14 women) and 31 subjects without marked hypercholesterolemia of the same age (control group; serum total cholesterol < 8 mmol/l) (15 men, 16 women). The three groups were comparable with respect to age, sex and body mass index. In the control group the mean sagittal thickness of AT was 4.5 mm (95% CI 3.2, 5.9 mm) and the mean coronal breadth of AT 11.0 (95% CI 9.0, 13.0 mm). Mean thickness of AT was 4.9 (range 4-7) mm in the non-FH group and 11.1 (5-16) mm in the FH group. The mean breadth of AT was in these groups 12.0 (10-17) mm and 19.2 (12-27) mm, respectively. Using the upper 95% confidence interval cut-off point in the control group as a criterion for normal AT thickness and breadth, 6 (22%) of non-FH and 29 (97%) of FH patients had increased AT thickness and 5 (19%) vs. 26 (87%) patients had increased AT breadth, respectively. The sensitivity of AT thickness for identifying FH was 0.97, specificity 0.78 and positive predictive value 0.83. The sensitivity of AT breadth in identifying FH was 0.87, specificity 0.81 and positive predictive value 0.84. None of the control subjects and none of the non-FH patients showed structural abnormalities of AT in the US, whereas 89% of FH-patients showed hypoechogenicity of AT. FH-score obtained by summing up the number of abnormal US findings gave a sensitivity of 0.93, a specificity of 0.96 and a positive predictive value of 0.96 for AT US in discriminating FH from non-FH. In conclusion, US examination of AT is a useful method in the detection of AT xanthomata and thus of help in the diagnosis of heterozygous FH.     

Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia

Familial hypercholesterolemia (FH) is characterized by severe hypercholesterolemia and premature coronary heart disease (CHD). The lower the plasma cholesterol level, the more likely it is that CHD can be prevented or retarded; aggressive cholesterol-lowering therapies may be indicated for FH patients with CHD. This study describes the long-term (6 years) safety and efficacy of intensive cholesterol-lowering therapies with low-density lipoprotein (LDL) apheresis in heterozygous FH patients with CHD. One hundred thirty heterozygous FH patients with CHD documented by coronary angiography had been treated by cholesterol-lowering drug therapy alone (n = 87) or LDL apheresis combined with cholesterol-lowering drugs (n = 43). Serum lipid levels and outcomes in each treatment group were compared after approximately 6 years. Both treatment groups had significant reductions in serum cholesterol, LDL cholesterol, and high density lipoprotein cholesterol levels. LDL apheresis significantly reduced LDL cholesterol levels from 7.42 ± 1.73 to 3.13 ± 0.80 mmol/L (58%) compared with group taking drug therapy, from 6.03 ± 1.32 to 4.32 ± 1.53 mmol/L (28%). With Kaplan-Meier analyses of the coronary events including nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, and death from CHD, the rate of total coronary events was 72% lower in the LDL-apheresis group (10%) than in drug therapy group (36%) (p = 0.0088). It is concluded that LDL-apheresis is effective as treatment of CHD in FH heterozygotes, and may become the therapy of choice in severe types of FH.     

Plasma lipid and lipoprotein concentrations in Chinese males with coronary artery disease, with and without hypertension

Plasma lipid and lipoprotein concentrations were determined in 125 Chinese males with a medical history and electrocardiographic abnormalities consistent with the diagnosis of coronary artery disease (CAD). All subjects underwent coronary arteriography, and patients were divided into 3 groups based upon the results of the coronary arteriograms: 1) patients with a negative angiogram (CAD-, n = 30), without hypertension; 2) patients with a positive angiogram, without hypertension (CAD+, n = 70); and 3) patients with a positive angiogram, who had hypertension (CAD + HT, n = 25). Mean fasting plasma lipid and lipoprotein concentrations of these 3 groups of patients were compared to values in age and weight-matched groups of normal individuals (n = 80) and untreated patients with hypertension and no evidence of CAD (HT, n = 20). The results indicated that total plasma triglyceride, cholesterol, and LDL-cholesterol levels were significantly higher (P less than 0.001) than normal in patients with CAD+ and CAD + HT, whereas only plasma cholesterol levels were higher than normal in patients with HT. Although patients with CAD- had values intermediate between normal and CAD, the differences were not statistically significant. In addition, the ratio of LDL to HDL-cholesterol was significantly increased (P less than 0.05-0.001) above normal in patients with CAD+, CAD + HT, and HT. As before, the values in patients with CAD- were intermediate. These data document the presence of multiple abnormalities of lipid and lipoprotein concentration in patients with angiographic evidence of CAD, whether or not they were hypertensive. Furthermore, abnormalities in lipid and lipoprotein metabolism were seen in patients with hypertension alone.     

Comparison of the risk factors for coronary artery spasm with those for organic stenosis in a Japanese population: role of cigarette smoking

We compared the risk factors for coronary spasm with those for coronary atherosclerosis in 183 patients with coronary spasm, 132 patients with coronary organic stenosis, and 224 control subjects with chest pain syndrome. Our findings confirmed that, when compared with controls, age, gender, total cholesterol, LDL-cholesterol, hypertension, diabetes mellitus, and cigarette smoking are all significant risk factors for coronary organic stenosis. On the other hand, only cigarette smoking proved to be a significant risk factor for coronary spasm. Also, when compared between coronary spasm group and coronary organic stenosis group, the incidence of cigarette smoking in males was significantly higher in the coronary spasm group than in the coronary organic stenosis group. We conclude that cigarette smoking is a crucial risk factor for coronary spasm. On the other hand, serum lipid levels and the incidence of hypertension and diabetes mellitus were within the normal ranges in the coronary spasm patients and were thus poorly associated with coronary spasm. These results showed that the risk factors for coronary spasm differ significantly from those for atherosclerosis-based coronary stenosis in the Japanese. Among the risk factors for coronary atherosclerosis (organic stenosis) smoking alone was a significant preventable risk factor for coronary artery spasm.     

The Retardation of Progression,Stabilization, and Regression of Coronary and Carotid Atherosclerosis by Low-Density Lipoprotein Apheresis in Patients with Familial Hypercholesterolemia

Abstract: The long-term effects of low-density lipoprotein (LDL) apheresis (LA) on the progression and regression of atherosclerosis were evaluated by angiographic and pathological findings as well as ultrasonography based studies, and the clinical significance of the treatment was evaluated. We studied 11 patients with familial hypercholesterolemia (FH), 2 with homozygous FH and 9 with severe heterozygous FH who received combined LA and drug therapy for a mean of 7.7 years. During the treatment period, the mean time-averaged level of LDL cholesterol was 181 ± 52 mg/dl. According to the coronary angiographic results, 3 patients showed regression, 6 patients showed progression, and 2 patients showed no change. Cardiac events occurred in 6 patients. We pathologically examined at autopsy the coronary arteries of 1 FH patient who had received long-term LA therapy before death. The results revealed the process of scarring of atheromatous plaque, suggesting pathological regression correlated with the angiographic regression shown in serial angiograms taken during LA treatment. It was further suggested that the formation of an eccentric thick end wall lesion rich in collagen fiber prevented atheromatous plaque from tearing off. However, the annual progression rate of the mean maximal intima-media thickness in the common carotid artery was 0.0002 mm/year in the LA group, which was significantly lower than the mean of 0.251 mm/year seen in the control group (drug therapy only group). In the patients with heterozygous FH (9 patients), the annual progression rate was lowered to 0.0023 mm/year, suggesting regression. The findings of the present study indicate that patients with severe FH refractory to drug treatment may benefit from more aggressive cholesterol lowering treatments such as LA combined with cholesterol lowering drug therapy. The progression of atherosclerosis may be prevented, plaque may be stabilized (regressed), and clinical events may be reduced as seen with patients with non-FH hypercholesterolemia.     

Coronary artery disease and bile acid synthesis in familial hypercholesterolemia

A cohort of 97 consecutive patients (mean age 43 years), heterozygous for familial hypercholesterolemia (FH) with tendon xanthomata, were studied to explore the possible association of coronary artery disease (CAD) with classical risk factors of CAD and parameters of cholesterol metabolism, including cholesterol and bile acid synthesis. Seventy percent of the patients had CAD. Male sex, advanced age (in females), increased blood pressure (in females), obesity (in males), short stature and clinical signs of tissue deposition of cholesterol were more common in the patients with than without CAD. Serum total and LDL-cholesterol and triglyceride levels were not associated with the presence of CAD. As compared with normolipidemic healthy subjects, studied under similar conditions, the bile acid synthesis was subnormal in FH. However, the low bile acid values were associated with CAD, especially in men, while the bile acid formation was within the normal limits in the healthy FH patients. The findings suggest that FH patients with a low bile acid synthesis have an increased risk to develop coronary heart disease by an unknown mechanism.     

Coronary artery ectasia in a patient with myocardial infarction

We report on a case of triple-vessel coronary artery ectasia (CAE) in a young patient. This patient presented with anterior wall myocardial infarction (MI) with post-infarct angina. His coronary angiogram revealed coronary artery ectasia involving the left anterior descending, circumflex and right coronary arteries.