Genotype at a major locus with large effects on apolipoprotein B levels predicts familial combined hyperlipidemia

A sample enriched for familial combined hyperlipidemia (FCHL) was examined for evidence of an association between genotype at an apolipoprotein B (apoB) elevating locus defined by complex segregation analysis and FCHL. Complex segregation analysis detected a locus with a large effect on plasma apoB levels and was used to compute the most probable genotype of family members. None of the 35 normolipidemic adults carried a copy of the allele associated with elevated apoB levels, yet 58% of the 109 adults with FCHL carried 1 (29%) or 2 (28%) copies. Two of 28 (7%) normal children had 1 copy of this allele and none had 2 copies, while 88 of 182 (48%) children with FCHL had 1 (26%) or 2 (22%) copies. Further, 4l of 48 (85%) individuals classified as having hyperapobetalipoproteinemia did not carry a copy of this “elevated apoB” allele. Therefore, the presence of the allele associated with elevation of apoB level is highly predictive of FCHL and this association cannot be explained solely by the presence of elevated apoB levels in FCHL, suggesting that the locus controlling apoB levels may play an etiologic role in FCHL. © 1993 Wiley-Liss, Inc.     

THE INCREASE OF FEMORAL ARTERIAL FLOW BY STIMULATING THE DORSAL AND VENTRAL MEDULLA IN CATS

1. In chloralose-urethane anaesthetized cats, the dorsal cardiovascular reactive area (DCRA) in the parvocellular reticular nucleus dorsomedial to the facial nucleus, and the ventral cardiovascular reactive area (VCRA) ventromedial to the facial nucleus, were stimulated by microinjections of sodium glutamate (100–200 nmol) or electric current. 2. Stimulation of DCRA, with a long latency of 15–20 s, elicited a marked increase of blood flow in the contralateral femoral artery with little change to moderate increase in systemic arterial blood pressure (ABP). In the relatively dorsal portion of DCRA, however, a smaller increase of blood flow in the ipsilateral femoral artery was elicited. 3. On the other hand, stimulation of VCRA with a short latency (3–5 s) evoked an increase of blood flow in both femoral arteries which was more prominent on the contralateral side. The responses were accompanied with decreases in the blood flow of other vascular beds with only a slight increase or minimal change in ABP. 4. The data suggest that DCRA and VCRA are both viscerotopically organized to alter the resistance of individual vascular beds for redistribution of blood flow.     

DIFFERENCES IN ENDOTHELIUM-DEPENDENT RELAXATION IN VARIOUS ARTERIES FROM WATANABE HERITABLE HYPERLIPIDAEMIC RABBITS WITH INCREASING AGE

1. Endothelium-dependent relaxation in response to acetylcholine (ACh) and the calcium ionophore A 23187 was examined in aorta, coronary, basilar and renal arteries isolated from Watanabe heritable hyperlipidaemic (WHHL) rabbits of 2, 6 and 12 months of age, with normolipidaemic heterozygous WHHL rabbits as controls. 2. In the rings of WHHL rabbit aortae and coronary arteries preconstricted with vasoconstrictors, endothelium-dependent relaxation in response to ACh was attenuated with age compared to the heterozygous WHHL rabbits. A significant negative correlation was found between the total cholesterol content and the relaxation response to ACh in the aortae or coronary arteries from 6 and 12 month old WHHL rabbits. 3. In the rings of basilar arteries, endothelium-dependent relaxations to ACh were not modified with age. Similarly, in the rings of renal arteries, the relaxation response to ACh was not changed with age, but in the 6 and 12 month preparations, after the age of 6 months, a contraction following the relaxation appeared at higher concentrations of ACh (10^?7 to 10^?6 mol/L). The contraction was endothelium-dependent and inhibited by indomethacin. 4. A 23187-induced endothelium-dependent relaxations were also markedly attenuated in the aorta and significantly in the coronary artery with age. 5. Endothelium-independent relaxation to sodium nitroprusside was not changed in all arteries from WHHL rabbits of different ages. 6. These findings indicate that in the aorta and coronary artery of the WHHL rabbit, the endothelium-dependent relaxation to ACh and A 23187 becomes impaired with increasing age (i.e., with the progression of cholesterol deposition in the arterial wall) but is preserved in the basilar and renal artery.     

THE INTERACTION BETWEEN ENALAPRILAT AND SELECTED α-ADRENOCEPTOR ANTAGONISTS IN ISOLATED RAT TAIL ARTERIES

1. Isolated perfused rat tail artery preparations were used to investigate the effects of the angiotensin converting enzyme inhibitor enalaprilat on the actions of a series of α-adrenoceptor antagonists. The agonist used was phenylephrine. 2. Enalaprilat (1 μmol/L) potentiated the competitive α₁-adrenoceptor antagonist actions of phentolamine (10–100 nmol/L) and yohimbine (0.3–3.0 μmol/L) as well as the non-competitive antagonist action of phenoxybenzamine (50–100 pmol/L). 3. The competitive α₁-adrenoceptor antagonist action of prazosin (1–10 nmol/L) was not affected by enalaprilat. 4. For the competitive α₁-adrenoceptor antagonists, including prazosin, there appeared to be an inverse relationship between antagonist potency and the extent of potentiation by enalaprilat. 5. The results support the hypothesis and angiotensin II modulates vascular smooth muscle α₁-adrenoceptor function.     

REOPERATION FOR RECURRENT CORONARY ARTERY DISEASE: RESULTS OF 200 CONSECUTIVE CASES

Background : It is well known that reoperation for recurrent coronary artery disease is more difficult than primary coronary artery bypass grafting. However, it is possible to reduce the morbidity and mortality of reoperation to the same level as the initial procedure with careful surgical technique. Methods : A retrospective study of the first 200 patients who underwent redo coronary bypass grafting was undertaken. Results : In the first 200 cases of redo coronary bypass grafting at St George Hospital, Sydney (August 1986–January 1995), there were five in-hospital deaths (2.5%). There was one case of sternal infection (0.5%), which required surgical debridement, three cases of stroke (1.5%), one case of postoperative bleeding (0.5%), which required a return to theatre and six cases (3%) required mechanical ventilation for more than 24h. The need for major postoperative support (such as intra-aortic balloon pumping/adrenaline infusion) was significantly affected by the degree of urgency and the degree of pre-operative ventricular impairment. Conclusions : The mortality rate of redo coronary artery bypass grafting in this series is similar to that of primary surgery described in other reports.     

Lipoprotein (a) levels in those with high molecular weight apo (a) isoforms may remain low in a significant proportion of patients with end-stage renal disease.

BACKGROUND: Studies have reported an increase in median Lipoprotein (Lp) (a) in patients with high molecular weight (HMW) apolipoprotein (apo) (a) isoforms and renal impairment. Some studies identify Lp (a) levels as a risk factor for vascular disease in renal failure whilst others have demonstrated an association with apo (a) isoform type and vascular disease. METHODS: A total of 239 patients at end-stage renal failure (ESRF) were studied prior to the initiation of dialysis. Blood was taken for Lp (a) levels and apo (a) isoforms. Clinical vascular disease (CVD) was assessed on the basis of clinical history and Rose questionnaire. The control group for Lp (a) levels consisted of 228 healthy volunteers. RESULTS: Despite a higher median Lp (a) level in those with HMW isoforms, 30% of patients had Lp (a) levels <10 mg/dl. Overall, 49% patients were identified as having CVD. Diabetes, smoking history and Lp (a) levels were significantly associated with CVD in logistic regression analysis, although when patients with low molecular weight (LMW) and HMW isoforms were analysed separately, Lp (a) levels were not significantly associated with CVD in those with LMW isoforms. The rates of CVD in those with HMW isoform and low Lp (a) levels were significantly lower than those with HMW isoforms and elevated Lp (a) levels, 34 vs 57% (P < 0.01). CONCLUSIONS: Although median Lp (a) levels in those patients at ESRF with HMW isoforms are higher than controls, in a third of such patients Lp (a) levels remain relatively low. These patients have lower rates of CVD than those with high levels of Lp (a).     

Carotid intima-media thickness in Parkinson's disease.

There have been a few studies and inconsistent results regarding the coincidence of Parkinson's disease (PD) and atherosclerotic diseases, such as cerebrovascular disease. Carotid intima-media thickness (IMT) is a known marker for subclinical atherosclerosis. The aim of this study was to investigate the carotid IMT between PD patients and controls. We studied 43 patients with PD and 86 matched controls. The carotid IMT in PD patients was significantly smaller than in controls (0.796 +/- 0.179 mm vs. 0.913 +/- 0.237 mm, P < 0.05). In multivariate analysis, the carotid IMT was inversely associated with the duration of levodopa medication and the severity of PD. These results suggest that PD patients have a lower risk of atherosclerosis.     

Cholesterol-based personal risk assessment in coronary heart disease

Using data from the National Health and Nutrition Examination Survey (NHANES II) 1976-1980, we demonstrate how cross-sectional total serum cholesterol surveillance data can be used by an individual to assess current and future personal cholesterol risk status. We propose statistical models, based on a person's current measured cholesterol level and the relationship between cross-sectional age and cholesterol percentile estimates, that will allow prediction of future cholesterol levels or the age at which specified cholesterol risk levels will be reached if no cholesterol-altering intervention is taken. These models incorporate the observed variation in the NHANES II data and expected intraperson biological variation and intralaboratory analytical variation. We illustrate the adequacy of the models using data from the longitudinal Framingham Study.     

Petrous internal carotid aneurysm causing epistaxis: balloon embolization with preservation of the parent vessel

Summary A patient with severe, recurrent posterior epistaxis was shown at angiography to have an aneurysm of the petrous portion of the internal carotid artery (ICA). Since childhood, she had had pain related to eustachian tube blockage by the aneurysm. An endovascular balloon embolization of the aneurysm was successful with preservation of the parent artery. The treatment resulted in resolution of the symtpoms. The report confirms the usefulness of an angiographic protocol in evaluating vascular problems.     

Von Willebrand factor, platelets and endothelial cell interactions

Summary.  The adhesive protein von Willebrand factor (VWF) contributes to platelet function by mediating the initiation and progression of thrombus formation at sites of vascular injury. In recent years there has been considerable progress in explaining the biological properties of VWF, including the structural and functional characteristics of specific domains. The mechanism of interaction between the VWF A1 domain and glycoprotein Ibα has been elucidated in detail, bringing us closer to understanding how this adhesive bond can oppose the fluid dynamic effects of rapidly flowing blood contributing to platelet adhesion and activation. Moreover, novel findings have been obtained on the link between regulation of VWF multimer size and microvascular thrombosis. This progress in basic research has provided critical information to define with greater precision the role of VWF in vascular biology and pathology, including its possible involvement in the onset of atherosclerosis and its acute thrombotic complications.