Carotid artery intima-media thickness and brachial artery flow-mediated vasodilation in asymptomatic Japanese male subjects amongst apolipoprotein E phenotypes.

BACKGROUND: Epidemiological studies suggest that apolipoprotein E (apoE) polymorphism influences plasma lipoprotein levels and the development of cardiovascular disease. OBJECTIVE: To clarify the role of apoE polymorphism as a risk factor for early atherosclerosis. DESIGN: Using a high-resolution ultrasound method, we investigated the association between apoE phenotypes, carotid intima-media thickness (CCA-IMT), and flow-mediated dilation in the brachial artery (brachial-FMD) in 96 healthy asymptomatic Japanese men (mean +/- SD age, 50 +/- 8 years). RESULTS: Serum cholesterol and LDL-cholesterol levels in subjects with E3E4 were highest and those with E2E3 were lowest (P < 0.05 and P < 0.05, respectively). The CCA-IMT in E3E4 subjects (0.76 +/- 0.17 mm) was greater than that in E2E3 and E3E3 (0.61 +/- 0.15 and 0.64 +/- 0.14 mm, respectively; P < 0.01). In contrast, there was no difference between brachial-FMD and apoE phenotypes (P=0.15). By univariate analysis, CCA-IMT was positively correlated with age (r=0.51, P < 0.01), LDL-chol/HDL-chol ratio (r=0.37, P < 0.01), triglycerides (r=0.23, P < 0.05), and negatively correlated with HDL-cholesterol (r=-0.31, P < 0.01). An association between CCA-IMT and the presence of E4 allele was also found (P < 0.05). Logistic regression analysis revealed that the presence of E4 allele was a higher risk for increased IMT (relative risk of 4.4, 95% CI 1.5-12.5), even after adjustment for age, LDL-cholesterol, blood pressure and other known risk factors. A negative correlation between brachial-FMD and CCA-IMT was also found in all subjects (r=-0.21, P < 0.05), being most apparent in the E3E4 subjects (r=-0.53, P < 0.02). CONCLUSION: ApoE4 phenotype was independently associated with an increased risk of carotid atherosclerosis and elevated LDL-cholesterol levels in asymptomatic middle-aged Japanese men.

Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis independently increase atherosclerotic vascular disease outcome in Japanese patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) have high mortality from atherosclerotic/atherothrombotic vascular disease (AVD). However, the role of an elevated plasma total homocysteine (tHcy) level as a risk factor is uncertain in ESRD. METHODS: We enrolled 55 ESRD patients in a prospective follow-up study in order to evaluate the prognostic significance of their tHcy levels, common methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, and other atherosclerotic risk factors, in combination with the results of B mode ultrasound for carotid arteries. RESULTS: Mean intima-media thickness of the common carotid artery (CCA-IMT) in ESRD patients was thicker than that in 102 age- and sex-matched healthy controls. Carotid plaque was more frequently present in patients compared with controls, as was calcified plaque more common in patients (p < 0.001). Plasma tHcy levels (mean +/- SD) in patients (39.1 +/- 27.2 nmol/ml) were higher than that (8.8 +/- 2.7 nmol/ml) in controls (p < 0.001). Folic acid was the major determinant of elevated tHcy levels in ESRD patients. During the follow-up period of 31 +/- 3 months, 14 patients had one or more AVD complications, and 10 consequently died from AVD causes. Proportional hazards modeling showed that 5-year intervals of age (relative risk of 2.95, 95% CI 1.62 - 5.37), 10 nmol/ml intervals of tHcy levels (relative risk of 2.31, 95% CI 1.31 - 4.08), and presence of diabetes mellitus (relative risk of 6.62, 95% CI 1.07 +/- 40.8) were independent predictors of future AVD events, and tHcy levels (relative risk of 2.67, 95% CI 1.29 - 5.52) and age (relative risk of 2.10, 95% CI 1.15 - 3.83) were those of AVD mortality. We also found a significant association between carotid plaque prevalence and AVD events (X(2) = 11.6, p = 0.001). CONCLUSION: Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis appeared to contribute independently to increase the risk of AVD outcome in Japanese patients with ESRD.

Reversible peritoneal calcification in a patient treated by CAPD.

The patient, a female, aged 65 years, developed diffuse peritoneal calcification nine years after commencing CAPD therapy. No abdominal symptoms or evidence of peritonitis were discovered during this period. Before peritoneal calcification was detected, a dialysate with a high glucose concentration (3.86%) had been used once daily for 16 months. In the case of this patient, it was not possible to discover any of the previous indicated etiologies of peritoneal calcification such as significantly elevated values for the product Ca x P, overt secondary hyperparathyroidism, or relapsing peritonitis. It was realized that the use of a high-glucose dialysate in a patient on long-term CAPD treatment had been one causative factor. After peritoneal calcification had been confirmed, the calcium concentration of the dialysate changed from 3.5 mEq/l to 2.5 mEq/l and the patient was put on a regime of 2.0 g alumigel (aluminum-containing phosphate binders) a day. Eight months later, a CT scan was taken. The peritoneal calcification has clearly been mitigated. At present, CAPD therapy is being continued in the absence of any abdominal symptoms.

[Alterations of Lp (a) lipoprotein in patients with chronic renal failure treated by continuous ambulatory peritoneal dialysis].

Cerebrovascular and cardiovascular diseases are important predictors for survival in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and account for about half the deaths in these patients. Lipoprotein(a) [Lp(a)] is known to show high values in diabetics with proteinuria, and albuminuric renal disease. The purpose of this study was to determine Lp(a) levels and to investigate the association of Lp(a) and atherosclerotic risk factors in patients treated by CAPD. Lp(a) concentration were measured in 20 CAPD patients in the age range 31 to 83 years. Mean (+/- SD) levels of serum Lp(a) were elevated in the CAPD patients compared to age, sex matched 17 controls (49.5 +/- 27.7 vs. 15.5 +/- 12.4 mg/dl, p < 0.001). The levels of Lp(a) were significantly higher in the diabetic CAPD patients than in non-diabetics. There were significant positive correlations between serum Lp(a) concentrations and fasting blood sugar. However, when the above two groups were matched for age, sex, body mass index and FBS, Lp(a) concentrations were also significantly higher in CAPD patients than those in normal controls. We found no statistically significant correlations of Lp(a) with either age, body mass index, blood pressure, serum lipoprotein, apoprotein, glycated hemoglobin, BUN, creatinine or serum protein levels. There were no correlations between serum Lp(a) levels and albumin and LP(a) concentrations in the dialysate in all CAPD patients. Along with assessment of other known established cardiovascular risk factors such as elevated blood pressure, atherogenic abnormalities of plasma lipids and lipoproteins, and impaired glucose tolerance, we suggest that elevated levels of Lp(a) may lead to the accelerated atherosclerosis in these patients.

[The correlation between pulse wave velocity and diabetic angiopathy].

Pulse wave velocity (PWV) of the aorta was measured in 40 patients with diabetes mellitus, in order to study the relation between PWV and diabetic angiopathy. The PWV was significantly faster in diabetic patients on oral hypoglycemic agents than in those on diet alone or on insulin. The PWV correlated significantly and positively with age, systolic blood pressure and urinary albumin index. The PWV significantly faster in diabetics with microalbuminuria than in those without this findings. It was concluded that PWV in addition to known risk factors such as elevated blood pressure, atherogenic abnormalities of plasma lipids and lipoproteins, and elevated blood glucose, may be a reliable index of diabetic micro- and macroangiopathy.

A study of the clinical significance of lipoprotein (a) in nephrotic syndrome.

Lipoprotein (Lp)(a) concentrations were measured in eight patients with nephrotic syndrome in the age range of 8 to 69 yrs. Mean (+/- SE) levels of serum Lp(a) were elevated in the nephrotic patients compared to controls (76.5 +/- 19.7 vs 18.6 +/- 0.9 mg/dl, p less than 0.001). After treatment with prednisolone, Lp(a) concentrations were decreased from 85.2 +/- 21.6 to 42.2 +/- 14.0 mg/dl. During the treatment, serum total cholesterol showed a negative correlation with serum albumin concentration. However, no correlation was noted between Lp(a) and serum albumin concentration. There were no significant correlations between Lp(a) and other lipoprotein lipid and apolipoprotein levels. It was concluded that hyperLp(a)aemia may be an independent risk factor in the development of premature atherosclerosis in patients with nephrotic syndrome.

[A study of clinical significance of Lp[a] lipoprotein in patients with chronic renal failure treated by hemodialysis].

Lipoprotein [a] (Lp[a]) is known to show high values in patients with ischemic heart disease (IHD). In the present study attempts were made to determine Lp[a] levels and to investigate the association of Lp[a] and other atherosclerotic risk factors in patients with chronic renal failure treated by hemodialysis. Lp[a] concentrations were measured in 30 hemodialysis patients in the age range 34 to 77 years. Mean (+/- SD) levels of serum Lp[a] were not elevated in the hemodialysis patients compared to controls (19.3 +/- 18.0 mg/dl vs. 18.3 +/- 10.4 mg/dl, respectively). We found no statistically significant correlation of Lp[a] with either cholesterol, triglycerides, HDL-C or apoproteins. However, compared with controls, more than fivefold as many of those hemodialysis patients had high risk (greater than 30 mg/dl) concentrations of Lp[a]. Lp[a] tended to increase in hemodialysis patients with diabetes mellitus and/or ischemic heart disease. In patients with high levels of Lp[a] (greater than 30 mg/dl), Lp[a] tended to correlate positively with cholesterol, LDL-, HDL-C, apo B or apo B/AI. Incidence of IHD was also elevated in these patients. Along with other known risk factors such as hyperlipidemia and hypertension, an increased concentration of Lp[a] may play an important role in accelerating development of atherosclerosis in this condition.

A case of hyperLp(a)aemia, associated with systemic lupus erythematosus, suffering from myocardial infarction and cerebral infarction.

We describe a case of systemic lupus erythematosus (SLE) with nephrotic syndrome who suffered from myocardial infarction and cerebral infarction associated with hyperLp(a)aemia. The proband was an 18-year-old Japanese male who was found to have hypercholesterolemia and hyperLp(a)aemia, with a serum total cholesterol level of 361 mg/dl and a serum Lp(a) level of 197 mg/dl. His father and mother showed higher Lp(a)levels (26 and 56 mg/dl, respectively) than those in normals (18 +/- 0.6 mg/dl, mean +/- SE). Lp(a)glycoprotein phenotypes were examined. The proband had the phenotype S2/4, which is associated with high Lp(a) concentration. His parents had the phenotype S3/4 and S2/4. No cardiovascular diseases were noted in other members of his family. After treatment with CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Lp(a) levels decreased from 197 to 121 mg/dl, but still remained abnormally high. LDL apheresis using a Liposorber system was attempted in this patient. Total and LDL cholesterol levels decreased by 57 and 62%, respectively. Lp(a) levels decreased by 68%. These results suggest that LDL apheresis may be an alternative therapy in drug resistant hyperLp(a)aemia.

Decreased serum cholesteryl-ester transfer activity in a patient with familial hyperalphalipoproteinemia.

Lipoprotein patterns and cholesteryl-ester transfer activity (CETA) were examined in a patient with familial hyperalphalipoproteinemia (FHALP). The proband was a 41-year-old Japanese male. He was found to have hypercholesterolemia, with a serum total cholesterol level of 382 mg/dl and a HDL-cholesterol level of 177 mg/dl. HDL showed a high cholesterol/Apo AI ratio. His father, all of his siblings and one of his children showed high HDL-cholesterol levels (91, 100, 70, 108, 75 and 98 mg/dl, respectively). These data suggest that all members of his family were heterozygotes. He had neither cutaneous or tendinous xanthomas nor any clinical signs of atherosclerosis. The proband appears to have only one-tenth of the normal level of CETA. However, the level of lipid-transfer protein I (LTP-I) activity was near normal. Thus, this patient is most likely to have an exaggerated level of LTP-I inhibitor(s). Effects of probucol on serum lipoprotein and apolipoprotein levels were studied in our patient. Treatment with 250 mg of probucol twice daily reduced total serum cholesterol, low density lipoprotein (LDL) and HDL-cholesterol levels by 33.32 and 33%, respectively. Apo AI, B and E levels decreased by 22, 16 and 35% respectively. HDL-cholesterol/Apo AI ratio decreased from 0.9 to 0.76. CETA showed no significant changes. However, cholesterol ester mass transfer increased from 10.8 to 14.9% after treatment with probucol. These results suggest that probucol appears to be a useful drug for FHALP.

[Heterotopic ossification in the skeletal muscle metastases of advanced stomach cancer].

The formation of heterotopic bone tissue in carcinomas of the gastrointestinal tract and/or their metastases is extremely rare. In a 74-year-old female with gastric adenocarcinoma, we observed extensive bone formation within metastases in the skeletal muscles. There are only 7 other cases of heterotopic bone formation in gastric cancer reported in the world literature. We suggest that heterotopic ossification in primary cancers and/or their metastases is probably the result of metaplasia of stromal fibroblasts into osteoblasts.

[Case of gastric cancer associated with acanthosis nigricans and meningeal carcinomatosis].

The patient was a 61-year-old man who initially complained of skin pigmentation. He was diagnosed as malignant acanthosis nigricans associated with gastric cancer (IIc advanced) in March 1981. Surgical excision of the stomach was performed in May 1981. In July 1981 he experienced headache, vomiting and muscle weakness. A diagnosis of meningeal carcinomatosis was made based on his clinical symptoms, spinal fluid examination and a computerized tomography scan. The intraventricular administration of cytosine arabinoside, methotrexate and hydrocortisone via the Ommaya reservoir resulted in complete remission. In November 1981 the patient died of bronchopneumonia and sepsis due to pancytopenia.