High Incidence Of Vascular Disease Research Articles

The influence of familial factors on the progression of IgA nephropathy.

Vascular risk factors in first degree relatives of patients with insulin dependent diabetes mellitus are known to increase the risk of that patient developing diabetic nephropathy. We explored the influence of vascular risk factors in first degree relatives on patients with stable (serum creatinine < 150 mumol/l for > 5 years) and progressive (serum creatinine > 200 mumol/l, and > 150% serum creatinine at presentation, after minimum follow-up at 2 years) IgA nephropathy (IgAN). We compared sodium-lithium countertransport activity (SLC Vmax), plasma lipoprotein(a) and von Willebrand factor (vWf) concentrations, incidence of vascular disease, and incidence of hypertension in 37 first degree relatives of 23 patients with stable IgAN and 33 first degree relatives of 17 patients with progressive IgAN. The two groups of relatives were comparable with respect to other risk factors: age, smoking, blood pressure, and plasma glucose, creatinine, cholesterol and triglyceride concentrations. SLC Vmax was higher in relatives of stable patients (mean 0.37 mmol/h/l RBC [S.D. 0.18] vs 0.30 [S.D. 0.09]; P = 0.034 two-sample t-test). There was no difference between the relatives of stable and progressive patients in plasma lipoprotein(a) concentration (median 11.5 mg/l vs 13.0: P = 0.45; 95% C.I. -12 to 3; Mann-Whitney test), plasma vWf concentration (149.4 IU/dl [S.D. 55.6] vs. 163.2 IU/dl [S.D. 57.3]; P = 0.31 two-sample t-test), or incidence of hypertension (13/37 [35.1%] vs 10/33 [30.3%]; chi 2 = 0.185; P = 0.667). Relatives of patients with progressive IgAN had a slightly higher incidence of vascular disease (10/33 [30.3%] vs 8/37 [21.6%]; chi 2 = 0.688; P = 0.407). Familial vascular risk may increase the likelihood of progressive renal failure in patients with IgAN but the influence is likely to be small and unrelated to the factors we measured. SLC Vmax was significantly higher in relatives of patients with stable disease which contrasts with data from other studies and is unexplained.

The treatment of hypertension in older people and its effect on cognitive function

The benefits of antihypertensive drug therapy for older people have been clearly established. Meta-analysis suggests a 12% reduction in all-cause mortality, a 20% reduction in coronary heart disease and a 36% reduction in stroke. The absolute benefits of treatment are great due to the high incidence of vascular disease among older people. Clinicians may nevertheless have been deterred from initiating treatment because of concerns regarding adverse effects on cognition, mood, functional ability and quality of life. Recent evidence from randomised controlled trials suggests that these concerns are groundless. In the light of this evidence it is therefore disturbing that up to 50% of all older people with hypertension may remain untreated; and in over 50% of those who are treated, blood pressure may be inadequately controlled.

Susceptibility of plasma low- and high-density lipoproteins to oxidation in patients with severe hyperhomocysteinemia

A moderate increase in plasma homocysteine is increasingly considered an important risk factor of atherosclerosis and thrombosis. However, the mechanisms by which hyperhomocysteinemia induces vascular disease are not well defined. In vitro studies suggest that cysteine and homocysteine can induce oxidative modification of low-density lipoproteins (LDL). This suggestion is relevant because lipoprotein oxidation is thought to play a key role in the development of atherosclerosis and in the triggering of thrombotic events. An attractive model to study this topic is provided by patients with classical homocystinuria, an inherited disease characterized by severe hyperhomocysteinemia and a high incidence of thromboembolisms. We investigated the existence of oxidized LDL and the susceptibility to oxidation of the plasma cholesterol-rich lipoproteins in six patients with severe hyperhomocysteinemia, most likely due to classical homocystinuria, and compared the results with matched controls. The proportion of electronegative LDL and the concentration of thiobarbituric acid reactive substances in native LDL and high-density lipoproteins (HDL) did not differ between patients and controls, suggesting that the proportion of modified lipoproteins is not increased in patients with severe hyperhomocysteinemia. The susceptibility to oxidative modification of plasma LDL and HDL was also similar in the two groups, although the patients had homocysteine levels 18.3-fold higher than controls. Thus, increased oxidative modification is not likely to be a relevant mechanism in explaining their high incidence of vascular disease. A possible explanation for the lack of increased susceptibility to oxidation, as would be expected for the metabolic blockade that cause classical homocystinuria, is the 4.1-fold decrease in the concentration of cysteine in the plasma of patients. As a result the total concentration of homocysteine plus cysteine was slightly lower in patients than in controls. This interpretation implies that more studies are needed on lipoprotein susceptibility to oxidation in patients in which both plasma homocysteine and cysteine concentrations are increased. This metabolic situation may be frequent in the population with moderate hyperhomocysteinemia and vascular disease.

Sudden bilateral sensorineural hearing loss.

Most cases of sudden sensorineural hearing loss (SHL) remain idiopathic, and the majority are unilateral. From 1989 to 1993, 823 patients with sudden SHL were evaluated. Of these, 14 (1.7%) had sudden bilateral SHL. We reviewed the charts of these 14 patients to compare sudden bilateral SHL with sudden unilateral SHL. Usually, bilateral SHL was asymmetric. Most bilateral cases received combined steroid and vasodilator treatment, while unilateral cases were more likely to receive only one of these treatments. By audiological criteria, 67% of bilateral SHL cases improved, while the improvement rate in unilateral SHL was 52%; however, this difference was not statistically significant. In bilateral SHL patients showing improvement, both ears responded. Bilateral SHL patients were older at the onset of hearing loss, had a higher incidence of vascular disease, and were more likely to have positive antinuclear antibody titer. Recognition of similarities and differences between sudden unilateral and bilateral SHL can help in counseling patients.

Lipoprotein abnormalities in hypertriglyceridaemic patients on long‐term haemodialysis

To analyse by ultracentrifugation in a zonal rotor the plasma lipoproteins in hypertriglyceridaemic patients on long-term haemodialysis. Case-control study. Tertiary referred care centre. Ten consecutive hypertriglyceridaemic patients on haemodialysis and 12 consecutive healthy controls. Plasma lipid and lipoprotein cholesterol concentrations, lipoprotein physical properties and compositions, apolipoprotein concentrations. Hypertriglyceridaemia in patients undergoing haemodialysis is characterized by an increased amount of small and slow floating very-low density lipoproteins (VLDL), higher concentrations of intermediate density lipoproteins (IDL) and small and dense low-density lipoprotein (LDL) particles; reduced levels of high-density lipoproteins (HDL), in particular of HDL2. The lipoprotein composition of such patients indicates reduced cholesterol ester and increased triglyceride content. Compared to controls, they have lower levels of plasma apolipoprotein A-I and A-II and higher B, C-II, C-III and E values. The lipoprotein abnormalities observed in hypertriglyceridaemic patients undergoing haemodialysis have recently been associated with an increased incidence of vascular complications and may in part explain the high incidence of vascular disease reported in these subjects.

Modifications of platelet phospholipid fatty acid composition in streptozocin-induced diabetic rats

Increased thromboxane A 2 (TXA 2) generation by platelets has been reported both in diabetic patients and streptozocin-induced diabetic rats. This increase is in contrast to the decreased prostacyclin (PGI 2) synthesis by endothelial cells in diabetes. An imbalance in the ratio of TXA 2/PGI 2 has been implicated in increased platelet aggregation and a high incidence of vascular disease in human diabetes. The mechanism for this imbalance, however, remains elusive. In a previous study from our laboratory, we reported unchanged arachidonic acid levels in platelet membrane phospholipids of 3-week diabetic rats, but a decreased arachidonic acid level in platelet membrane phospholipids of 6-week diabetic rats. In the present communication, we report the role of enzymes that are involved in remodeling arachidonic acid levels of platelet membrane phospholipids in both 3- and 6-week diabetic rats. No alterations were observed in the activities of arachidonoyl-CoA synthetase, acyl-CoA: lysophosphatidylcholine acyltransferase, or phospholipase A 2 in platelets from both 3- and 6-week diabetic rats. However, both increased uptake and incorporation of [ 14C]arachidonic acid into platelets were observed in the diabetic platelet-rich plasma. In conclusion, increased TXA 2 formation in diabetic platelets is not due to alterations in the activities of enzymes involved in the incorporation into or release of arachidonate from the diabetic platelet membrane phospholipid, but may be due to increased efficiency of uptake, incorporation or possibly redistribution of this fatty acid among phospholipid classes in diabetic platelets.

Anaesthesia for abdominal aortic surgery--a review (Part II).

Patients presenting for abdominal aortic surgery have a high incidence of vascular disease elsewhere, manifested primarily by hypertension, coronary and cerebrovascular disease, as well as co-existing respiratory, renal and metabolic disorders. Routine clinical assessment, electrocardiogram, chest roentgenograms, resting and exercise radionuclide ventriculography and echocardiography, dipyrdiamole-thallium scanning are all designed to assess the functional status of the myocardium and to detect the presence of significant coronary artery disease. Patients with no abnormalities on physical examination, routine evaluation and no redistribution on dipyridamole-thallium scanning should proceed to surgery with the expectation of very low perioperative cardiac risk. Patients with evidence of coronary artery disease and significant redistribution on dipyridamole-thallium scan should undergo coronary angiography and possible myocardial revascularization before definitive aortic vascular surgery. For high cardiac risk patients with no bypassable lesions presenting for abdominal aortic aneurysm resection a conservative policy of serial three monthly ultrasound or CT assessment may be adopted, with selective resection for rapid aneurysm expansion or symptom development. A variety of extra-anatomical and angioplastic techniques is available for similar high cardiac risk patients with aortoiliac occlusive disease. The haemodynamic consequences of aortic cross-clamping, especially in aneurysm patients, include a significant reduction in stroke volume, cardiac index, and myocardial oxygen consumption with an increased systemic vascular resistance. Patients with coronary artery disease may respond to aortic cross-clamping by increasing pulmonary capillary wedge pressure and by demonstrating ECG evidence of myocardial ischaemia. Pulmonary artery catheterization is especially indicated in patients with a history of previous myocardial infarction, angina or signs of cardiac failure and in patients with evidence of diminished ejection fraction, abnormal ventricular wall motion or myocardial redistribution on preoperative scanning. The more widespread application of intraoperative transoesophageal two-dimensional echocardiography and radionuclide cardiography monitoring techniques into anaesthetic practice will enable measurement of left ventricular dimensions, myocardial performance and wall motion. Suggested guidelines for anaesthetic management are presented in Table VI. A combined opiate-oxygen-volatile anaesthetic agent technique will best ensure a hypodynamic circulation with preservation of myocardial oxygenation.(ABSTRACT TRUNCATED AT 400 WORDS)

US location of the adductor canal hiatus: morphologic study.

In the lower extremities, the adductor canal hiatus is a site of predilection for arterial stenoses and occlusions. The high incidence of vascular disease in this region is thought to be due to a local factor. To gain more insight into the mechanisms leading to such disease, the authors used ultrasound to locate the adductor canal hiatus in dissecting room preparations and in healthy volunteers.

Adverse Effects of Amiodarone

<h3>To the Editor.—</h3> The recent article by Nademanee and Singh (1982;247:217) did not emphasize the significant potential adverse reactions that we have noted in 100 patients receiving a mean dosage of 461 mg/day of amiodarone hydrochloride. Transient ischemic attacks have occurred in four of our patients and cerebral vascular accidents have occurred in three patients after initiation of amiodarone therapy (followup, one to 20 months; mean, 6.6 months). While our patients have a high incidence of vascular disease, only five patients had cerebral vascular accidents before the initiation of amiodarone therapy. We hope that this will not prove to be a long-term sequelae of amiodarone therapy. Weakness, fatigue, a nonproductive cough, and dyspnea have been symptoms that have responded to diuresis. None of our patients required cessation of therapy because of the adult respiratory distress syndrome. We have reported previously¹a grading system for amiodarone keratopathy. However, we neglected to

INSULIN AND ATHEROMA

New information on carbohydrate and lipid metabolism has resulted in reappraisal of ideas of the underlying abnormalities in diabetes and atherosclerosis. It is noted that the incidence of diabetic arteriopathy has increased in spite of control of hyperglycemia and ketosis by insulin and that many nondiabetic persons with coronary artery disease have abnormalities or carbohydrate and lipid metabolism similar to those found in diabetics. Some patients secrete abnormally large amounts of insulin in response to dietary carbohydrate; these people have a particularly high incidence of vascular disease. Physicial excercise lowers insulin requirements. Synalbumin increased serum lipids in the forms of cholesterol triglycerides and the endogenous type of hyperlipidemia induced by dietary carbohydrate have been related to the incidence of coronary artery disease. The insulin response produced by the carbohydrate diet is related to the hepatic-triglyceride-secretion rate and is considered to be the primary cause of elevated serum-triglyceride. A similar mechanism is assumed for serum-cholesterol regulation. Hyperinsulinism is found in obesity in patients with hypertension and in some women who have been taking oral contraceptives for more than 1 year. These women also show elevated triglycerides and pre-beta-lipoprotein levels. It has been reported that these women also have an increased risk of vascular diseas e. The evidence incriminating insulin and carbohydrate is considered strong and would link atherosclerosis with diabetes obesity hyperlipidemia lack of physical exercise and possibly hypertention and use of contraceptive drugs.