Aortic valve calcium score in hypercholesterolemic patients with and without low-density lipoprotein receptor gene mutation.

The aim of this study was a comparison of aortic valve calcium score (AVCS) between patients with hypercholesterolemia and genetic diagnosis of familial hypercholesterolemia with low-density lipoprotein receptor gene mutation (LDLR-M group), versus patients with hypercholesterolemia without LDLR gene mutation (LDLR-WT group). A total of 72 LDLR-M patients and 50 LDLR-WT patients were enrolled in the study and underwent CT as a part of an assessment of coronary calcium scoring. AVCS was determined and compared between the two patient groups. AVCS was significantly higher in the LDLR-M group in comparison to the LDLR-WT group (13.8 ± 37.9 vs. 0.94 ± 3.1, p = 0.03). The Yates' chi-squared test for independence revealed that LDLR mutation and AVCS were significantly dependable (Chi^2 = 6.106, p = 0.013). The LDLR mutation was a strong predictor of a high AVCS (OR 7.83, 95% CI 2.08-29.50, p = 0.002) on multivariate regression analysis. Among the traditional risk factors, age (odds ratio 1.12, 95% CI 1.05-1.18, p<0.001) and SBP (OR 1.04, 95% CI 1.00-1.07, p = 0.045) were also significant for high result of AVCS. An assessment of computed tomography calcium scores showed that LDLR-M patients have increased AVCS in comparison to those with LDLR-WT. In addition, LDLR mutation can be considered as an independent risk factor of having high AVSC even after adjustment for risk factors including cholesterol levels. This may result from the associated process connected with the regulatory role of LDLR in evolution of aortic valve calcifications.

Protective modulation of carotid atherosclerosis in hyperalphalipoproteinemic individuals.

To determine whether hyperalphalipoproteinemia modifies carotid intima-media thickness (cIMT) and/or influences the relationship of clinical and biochemical parameters with cIMT. This study was conducted on 169 asymptomatic individuals, classified as hyperalphalipoproteinemic (Hyper-A) (Hyper-A, n = 71, HDL-C > or =68 mg/dL) and controls (CTL) (CTL, n = 98, HDL-C >32 and <68 mg/dL). Enzymatic, nephelometric and ultracentrifugation methods were used for biochemical determinations. Hepatic lipase (HL), lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and phospholipids transfer protein (PLTP) activities were measured by radiometric exogenous methods. The prevalence of dyslipidemia, hypertension, smoking, sedentariness, postmenopausal women, coronary artery disease (CAD) and familial history of CAD were determined. High resolution beta-mode carotid ultrassonography was performed. The Hyper-A group was older and had higher frequencies of hypercholesterolemia (40%), hypertension (31%), sedentariness (37%) and postmenopausal women (1%). In Hyper-A individuals, the mean cIMT after adjustment for age and gender was similar between the groups (0.85 +/- 0.24 mm Hyper-A versus 0.69 +/- 0.17 mm CTL). In multivariate models, age was a significant predictor of cIMT in Hyper-A (R (2) = 0.04, p < or = 0.001), independently of other clinical or biochemical factors. In contrast to CTL, where age (R (2) = 0.63 p < or = 0.001), male sex (R (2) = 0.03, p < or = 0.001), blood pressure (R (2) = 0.006, p < or = 0.001) and HDL-C (R (2) = 0.02, p < 0.022) accounted for the cIMT variations. Despite an increased prevalence of cardiovascular risk factors in Hyper-A and resistance of carotid thickness to modulation by metabolic and anthropometric factors (except age), the similarity in cIMT between Hyper-A and healthy individuals emphasizes the atheroprotective effects of HDL.

A case of marked hyperlipoprotein(a)emia associated with nephrotic syndrome and advanced atherosclerosis.

In 1989, we encountered a 68-year-old male patient with marked hyperlipoprotein(a)emia (hyperLp(a)emia), who was being treated for hypertension and arteriosclerotic obliterans (ASO) at an outpatient clinic of our hospital. He began to develop leg edema in 2002 and was referred to the Department of Internal Medicine. It was determined that he had severe hyperlipidemia (total cholesterol, 362 mg/dl), proteinuria, and hypoalbuminemia, suggesting the presence of nephrotic syndrome. On lipoprotein analysis, he was found to have very high levels of Lp(a) in the plasma (329 mg/dl). Severe atherosclerosis was also found: that is, abdominal aortic aneurysm (AAA) and coronary artery disease (CAD) were detected, in addition to ASO. After remission of the nephrotic syndrome, the plasma Lp(a) level decreased to 204 mg/dl and the total cholesterol concentration decreased to 179 mg/dl, while very high levels of Lp(a) persisted. We estimate that the markedly elevated Lp(a) plasma levels in this patient may have played some role in the progression of atherosclerosis.

[Dilatation of the popliteal artery in hyperemia and intimal-medial thickness of the carotid artery in hyperlipoproteinemia, ischemic heart disease and in healthy individuals]. / Schopnost dilatace podkolenní tepny pri hyperemii a intimomediální tloustka krkavic u pacientu s hyperlipoproteinemiemi, s ischemickou chorobou srdecní a u zdravých osob.

Non-invasive measurement of the intima-media thickness (IMT) of the carotid artery and flow-mediated dilatation (FMD) of the brachial artery are increasingly used as surrogate markers of vascular disease. Using ultrasound, we measured the diameter of the popliteal artery at rest and during reactive hyperaemia after release of 5-minute arterial occlusion. We also measured IMT of the common carotid artery. In 29 control subjects (average age 35 years) we demonstrated an increase in the diameter by 6.0 +/- 3.3% (p < 0.05), in 29 asymptomatic patients with hyperlipidemia (without therapy, average age 46 years) only by 0.9 +/- 3.0% and in patients with coronary heart disease (average age 50 years) only by 0.2 +/- 2.7%. The difference between patients and control subjects was highly significant (p < 0.001). IMT was 0.58 +/- 0.10 mm, 0.78 +/- 0.17 mm and 1.03 +/- 0.25 mm respectively (p < 0.001). We conclude that in patients FMD of the popliteal artery is smaller and IMT of the common carotid artery is thicker than in controls.

[Usefulness of doppler ultrasonography in diagnosing changes in atherosclerotic lesions in lower extremity arteries in hyperlipoproteinemia]. / Przydatnosc sonografii dopplerowskiej w diagnostyce zmian miazdzycowych tetnic konczyn dolnych w hyperlipoproteinemii.

The purpose of this study was to establish the correlation between the intensity of atherosclerosis of the lower extremities found in the course of the Doppler examination, and type of hyperlipoproteinaemia. An attempt was undertaken to analyse the relation of the risk factors of obliterative atherosclerosis to the condition of the arteries in the lower extremities. 53 men at the age of 37 to 63 years (mean age 51 years) were examined. HLP type IIa, IIb, IV, was found in 16, 19, 18 patients respectively. The control group consisted of 30 healthy non-smoking men. The examination was performed using ACUSON 128 with a linear probe 5 and 7 MHz. The Doppler spectrum was registered from the external iliac, common femoral, superficial femoral, deep femoral and popliteal arteries. Simultaneously, a two-dimensional color picture of contrasted vessels, and the Doppler spectrum of blood velocity were recorded. Blood velocity spectrum was quantitatively assessed according to the classification suggested by Jager et al. The results of the Doppler examination confirmed the unfavourable influence of the so called risk factors on the progress of atherosclerosis, especially low serum concentration of HDL cholesterol and cigarette smoking. Besides, the examination has proved the possibility to diagnose even asymptomatic atherosclerotic lesions of the arteries of lower extremities.

[The intima of the common carotid artery in patients with hyperlipoproteinemia]. / Posuzování intimy arteria carotis communis u nemocných s hyperlipoproteinémií.

Using sonography, the common carotid artery was examined in patients with hyperlipoproteinaemia and in controls. In 21 controls, the intima was present in 62%, intimal thickness was 0.41 +/- 0.14 mm. In patients with familial hypercholesterolaemia free of ischaemic heart disease (46 patients), the intima was demonstrable in 89%, intimal thickness was 0.74 +/- 0.21 mm. In patients with ischaemic heart disease (19 patients), the intima could be demonstrated in 100%, its thickness was 0.84 +/- 0.31 mm. In 21 patients with familial combined hyperlipoproteinaemia, the intima was present in 90%, intimal thickness was 0.73 +/- 0.17 mm. Intimal thickness was significantly greater (p < 0.001) in all groups of patients with hyperlipoproteinaemia than in the control group. A significant correlation between cholesterol levels and intimal thickness (p < 0.01) was demonstrated.

[In vivo flow of autologous radioactively labeled low-density lipoproteins (LDL) in human blood vessels]. / In-vivo-Einstrom autologer radioaktiv markierter Low-density-Lipoproteine (LDL) in menschliche Gefässe.

Following 123I-labelling and reinjection of autologous low-density lipoproteins (LDL) to patients with clinically manifest atherosclerosis and/or hyperlipoproteinaemia (HLP), an investigation was carried out of whole body kinetics and local kinetics over atherosclerotic lesions and areas of increased LDL entry identified by "hot spots" in the 123I-LDL scintigram. In patients with HLP the number and frequency of "hot spots" was higher than in normolipaemics. The time course of 123I-LDL influx into atherosclerotic lesion sites until scintigraphic visualization of "hot spots" exhibited three different types of LDL uptake among the patients. In the majority of patients LDL kinetics was characterized by entry into the vessels with the maximal radioactivity measured as early as within 60 minutes after reinjection. In some patients maximal radioactivity over lesion sites was discovered after 20 hours or even later. Morphological evaluation revealed that in comparison to control tissue, fatty streaks and lipid lesions show by far the highest 123I-LDL accumulation. Ex vivo measurement of the deposition of 125I-LDL in de- and re-endothelialized rabbit aortic segments exhibited a significantly (p less than 0.01 - p less than 0.001) higher 125I-LDL retention as compared with endothelialized segments (after i.v.-injection).

[Technic of radioactive labeling of autologous human thrombocytes using 111-indium-oxine and 111-indium-oxine-sulfate and their clinical use]. / Technik der radioaktiven Markierung autologer menschlicher Thrombozyten mit 111-Indium-Oxin und 111-Indium-Oxin-Sulfat und deren klinische Anwendung.

Using 111indium oxine and 111indium oxine sulphate as platelet labels, maximal labelling efficiency can be achieved already after 3 minutes at an incubation temperature of 37 degrees C. Mean labelling efficiency values of about 90% are reached at a platelet count of greater than 10(9) platelets/ml, but the labelling efficiency is satisfactory also at a rather low platelet count of about 10(6) platelets/ml (71% on average). Platelet labelling with these tracers allows the calculation of platelet half-life in vivo, and gamma-camera imaging of platelet aggregates in thrombosis and renal transplant rejection as well. In the present study, the platelet half-life is significantly shortened in patients with coronary heart disease (n = 15), peripheral vascular disease (n = 13) and primary hyperlipoproteinaemia (n = 32) in comparison with 106 controls. No age dependence of platelet half-life was found in the different groups of patients whereas in the control group, a significant negative correlation between age and platelet half-life was observed.

Cerebrovascular arteriopathy (arteriosclerosis) and ischemic childhood stroke.

The aim of this report is to describe the intracranial cerebrovascular abnormalities and clinical status of 8 children who had familial lipoprotein disorders and evidence of thromboembolic cerebrovascular disease. Six of the 8 children had low levels of plasma high density lipoprotein cholesterol, two had high triglyceride levels, and all came from kindreds characterized by familial lipoprotein abnormalities and premature cardio- and/or cerebrovascular atherosclerosis. Vascular occlusion, irregularities of the arterial lumen, beading, tortuosity, and evidence of collateralization were consistently noted. We speculate that cerebrovascular arteriosclerosis in pediatric ischemic stroke victims who have familial lipoprotein abnormalities may be related to lipoprotein-mediated endothelial damage and thrombosis formation, or to the failure to restore endothelial cells' integrity following damage. The apparent association of lipoproteins and strokes in children and their families merits further exploration, particularly when assessing cerebral angiograms in pediatric ischemic stroke victims. In children with unexplained ischemic cerebrovascular accidents, the diagnostic possibility of occlusive arteriosclerosis with thrombosis must be entertained.