Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease

BACKGROUND: A family history of premature coronary artery disease (CAD) in a first-degree relative is an independent risk factor for coronary disease. Both genetic and environmental influences are likely to be responsible and may interact, but their relative importance is unclear. METHODS AND RESULTS: We studied endothelial function in 50 first-degree relatives (31 men, 19 women; mean age, 25+/-8 years) of patients (men < or = 45 years, women < or = 55 years) with proven CAD. All subjects were well, lifelong nonsmokers, not diabetic, and not hypertensive and took no medications. Using high-resolution external vascular ultrasound, we measured brachial artery diameter at rest and in response to reactive hyperemia (with increased flow causing an endothelium-dependent vasodilatation) and to sublingual glyceryltrinitrate (GTN, an endothelium-independent dilator). Vascular responses were compared with those of 50 healthy control subjects matched for age and sex. Flow-mediated dilatation (FMD) was impaired in the family history group (4.9+/-4.6% versus 8.3+/-3.5% in control subjects, P<.005). In contrast, GTN caused dilatation in all subjects (family history, 17.1+/-8.8%; control subjects, 19.0+/-6.3%; P=NS), suggesting that reduced FMD was due to endothelial dysfunction. When the family history subjects were subdivided, those found to have a serum cholesterol > 4.2 mmol/L (group A, n=10) had mildly impaired FMD compared with control subjects (5.5+/-5.1% versus 8.3+/-3.5%). In others whose affected relative had coronary risk factors (group B, n=24), FMD was also only slightly reduced (6.2+/-4.8% versus 8.3+/-3.5%). In contrast, subjects with no risk factors and whose affected relative had a normal cardiovascular risk factor profile (group C, n=16) had markedly impaired FMD (2.9+/-3.7% versus 8.3+/-3.5%). Although ANOVA of the three family history subgroups did not reach statistical significance (F=2.55, P=.09), pairwise analysis showed that FMD in group C was significantly impaired compared with group B (P=.026). CONCLUSIONS: Healthy young adults with a family history of premature coronary disease may have impaired endothelium-dependent dilatation, even in the absence of other cardiovascular risk factors. Those subjects, who were free of risk factors and whose affected first-degree relative was free of risk factors, had the most impaired endothelial function, suggesting a genetic influence on early arterial physiology that may be relevant to later clinical disease.     

Erythrocyte sodium and potassium in patients with hypokalaemia

1. The erythrocyte content of sodium and of potassium were measured in 231 unselected patients with hypokalaemia, and together with net ouabain-sensitive sodium efflux in patients with severe hypokalaemia, before (20 patients) and during potassium repletion (14 patients). 2. The erythrocytes of the patients with hypokalaemia compared with control subjects had on average an increase in sodium content, a decrease in potassium content and a reduction in the rate constant of ouabain-sensitive sodium efflux. All three changes had a similar curvilinear relation to the concentration of potassium in plasma with relatively little change in the measured variable unless the plasma potassium was very low. 3. There was a similar curvilinear relation between the final sodium and potassium content of normal erythrocytes and the potassium concentration of the medium in which they were incubated for 48 h in vitro. 4. These results suggest that the changes in the sodium and potassium content of erythrocytes in hypokalaemia are due to a direct inhibiting effect of the hypokalaemia on the activity of the sodium pump. 5. In many patients with hypokalaemia of moderate degree the increase in erythrocyte sodium content was less than expected from the effect in vitro of a low extracellular potassium concentration. This finding suggests that a compensatory change, presumably an increase in the number of sodium pumps, is a common event even in moderate hypokalaemia.     

Family history of coronary heart disease is a stronger predictor of coronary heart disease morbidity and mortality than family history of non-insulin dependent diabetes mellitus

The aim of this study was to compare the effect of family history of non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD) as risk factors for CHD morbidity and mortality. Altogether, 394 siblings of NIDDM probands and non-diabetic probands, with and without CHD, were followed for 8 years with respect to CHD events in a prospective population-based study. The baseline study was conducted from 1983 to 1985. Age- and sex-adjusted cumulative occurrence of CHD events was higher in the siblings of the probands with CHD and with NIDDM (13.1%; P = 0.037) and in the siblings of the probands with CHD and without NIDDM (15.4%; P = 0.054), compared with the siblings of the probands without NIDDM and without CHD (4.8%). The incidence of fatal CHD events tended to be higher in a group with a family history of NIDDM and CHD, but the trend was not statistically significant. In univariate logistic regression analyses, a family history of CHD was positively associated with cumulative occurrence of CHD events (odds ratio 2.53, P = 0.009), whereas a family history of NIDDM had no significant association (odds ratio 1.39, P = 0.312). After adjustment for age, sex, family history of NIDDM and major cardiovascular risk factors, the association between family history of CHD and cumulative occurrence of CHD events remained significant (odds ratio 2.25, P = 0.048). In conclusion, the present study indicates that a family history of CHD is a stronger predictor of future CHD events than a family history of NIDDM.     

Genetic heterogeneity of ischemic (coronary) heart disease

Results are presented on a study of the blood coagulation system and some indices of serum lipids and proteins in 133 normal individuals and probands with ischaemic heart disease and their 681 relatives. The examination of the relatives of probands with different types of biochemical disorders revealed a similar biochemical background in the probands and the members of their families. The disorders in blood biochemistry in the probands were most similar in the parents, the children of the probands' siblings, and less distinct in more distant relatives (cousins, nephews and nieces, etc.), biochemical disorders similar to those of the probands being found in young persons (14-16 years old) and reappearing in several generations. The author concludes on the genetic heterogeneity of ischaemic (coronary) heart disease and underlying coronary atherosclerosis.     

A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease

Lipoprotein lipase degrades triglycerides in plasma and as a byproduct produces HDL particles. Genetic variation in lipoprotein lipase may therefore affect cardiovascular risk. We tested 9,214 men and women from a general population sample and 948 patients with ischemic heart disease for the Asn291Ser substitution in lipoprotein lipase. The allele frequency in the general population was 0.024 and 0.026 for women and men, respectively. In comparison with noncarriers, female heterozygous probands had increased plasma triglycerides (delta = 0.23 mmol/liter), while HDL cholesterol was reduced in both female and male carriers (delta = 0.18 mmol/liter and delta = 0.11 mmol/liter, respectively). A similar phenotype was found in six homozygous carriers. On multiple logistic regression analysis, plasma triglycerides and HDL cholesterol were independent predictors of ischemic heart disease in both genders. On univariate analysis, odds ratios for ischemic heart disease in probands were 1.89 in women (95% CI: 1.19-3.01) and 0.90 in men (95% CI: 0.62-1.31), and on multivariate analysis were 1.98 in women (95% CI: 1.11-3.53) and 1.02 in men (95% CI: 0.65-1.60). This study demonstrates that a single common mutation in the lipoprotein lipase gene is associated with elevated plasma triglycerides and reduced HDL cholesterol levels, whereby carriers, in particular women, seem to be predisposed to ischemic heart disease. It cannot be excluded, however, that male carriers of this substitution may represent a subset of low-HDL individuals without raised triglycerides not predisposed to ischemic heart disease.     

Digitalis effects on the electrocardiogramm: ergometric studies in healthy subjects and patients with coronary artery disease (author's transl)

Therapeutically effective doses of beta-acetyldigoxin in healthy subjects produced no or only minor S-T depression both at rest and under maximal cycle-ergometry, in individual instances the S-T segment never being depressed by more than 0.1 mV. On the other hand, similar exercise in patients with latent coronary insufficiency produced marked, significantly and dose-dependent S-T segment depressions under increasing digitalisation within the therapeutic range, and in some of the patients there was also decreased exercise tolerance before anginal symptoms. It is concluded that the so-called digitalis effect is definitely of diagnostic significance in the recognition of latent coronary insufficiency, contrary to previously held belief.     

Outcomes of balloon coronary angioplasty of bifurcation stenoses in patients with ischemic heart disease

Specialists of the Research Institute of Urology have practiced combination of transurethral resection (TUR) with electrovaporization in endoscopic treatment of bladder cancer (BC) since 1995. A total of 46 patients with transient cell BC (29 males and 17 females aged 49-87) stage Ta-T1 (32 patients) and T2-T3b (14 patients) underwent TUR or electrovaporization (if morphologically verified) of the exophytic part of the tumor. In addition, electrovaporization of the base of the tumor was made. Main indications for such treatment were standard indications for TUR in contraindications for more radical treatment. 6-24-month follow-up was possible in 23(71.9%) patients with superficial BC (group 1) and in 9(64.2%) patients with invasive BC (group 2). Endoscopically, the recurrence was detected in 3(13%) and 5(55.5%) patients of group 1 and 2, respectively. They were reoperated on with electrovaporization. It is inferred that TUR-vaporization of the bladder is an effective endoscopic treatment of superficial BC. Electrovaporization is a good palliative treatment in patients with invasive BC when radical surgery is impossible. It inhibits the progression of the disease, prevents hemorrhages due to the tumor destruction, reduces intraoperative blood loss, improves endoscopic visualization. It may also increase the operation ablasticity.     

Oxidation of remnant-like particles from serum of diabetic patients, patients with ischemic heart disease and normal subjects

Remnant-like particles (RLP) are reportedly involved in the pathogenesis of atherosclerosis, as are lipid peroxides. To assess the role of the oxidation of RLP in this disease, we compared the oxidation of RLP with that of total very low density lipoproteins (VLDL) obtained from the serum of 10 patients with ischemic heart disease (IHD), 10 patients with diabetes mellitus (DM) and 10 normal subjects by measuring the levels of thiobarbituric acid reactive substances (TBARS). Our results indicated that RLP were oxidized in vivo to a greater extent than total VLDL in all three groups of subjects. The serum levels of RLP were significantly higher in the patients than in the normal subjects. The oxidation of RLP may therefore be involved in the progression of atherosclerosis in patients with IHD or DM.     

A novel approach to assessing family history in the prevention of coronary heart disease

Although the fundamentals of Endovascular Surgery were set down over 30 years ago, only recently has the potential impact of this therapy become readily apparent. Endovascular therapies with new instrumentation for the treatment of arterial aneurysms, occlusions, trauma, and venous thrombotic disorders have progressed dramatically over the past 5 years. Guidewire and catheter techniques for endovascular instrumentation of vessels have also been shown to compliment standard vascular surgical interventions. The need for vascular surgeons to obtain the knowledge and professional skills to perform wire and catheter techniques is essential to convert the professional "threat" of endovascular surgery to a future of "opportunity."     

Perioperative cardiac arrhythmias in digitalized patients with ischemic heart disease (author's transl)

The purpose of this study was to establish the incidence of pre-operative digitalization by intravenous digoxin on cardiac arrhythmias in 24 patients with ischemic heart disease who underwent abdominal surgery. Ambulatory electrocardiographic monitoring was performed for 12 hours before digitalization, for 12 hours during digitalization (before surgery), for the whole period of anesthesia. General anesthesia used thiopentone, phenoperidine, pancuronium and suxamethonium for endotracheal intubation. No more premature ventricular (PVC) and auricular contractions were detected after digitalization and during anesthesia and surgery. But PVC with begeminism or severe bradycardia were recorded in two patients and episodes of "torsades de pointes" occurred in two other patients during endotracheal intubation. "Torsades de pointes" have never been reported after suxamethonium and endotracheal intubation in digitalized patients. Digitalization, ischemic heart disease, cardiac effects of suxamethonium might be factors of the onset of these first reported "torsades de pointes". In conclusion, after a pre-operative digitalization in the coronary patients the frequency of arrhythmias is not exaggerated during the pre- or per-operative period except during induction and intubation. As the role of suxamethonium seems to be important as a trigger for severe arrhythmias endotracheal intubation in digitalized coronary patients should be performed without suxamethonium.     

Cholesterol and lipoprotein(a) as risk factors for coronary heart disease in elderly subjects

The changes in lipoprotein(a) concentration that occur with age as a result of its association with an increased risk of coronary artery disease were investigated. Lipoprotein(a) concentrations were measured in serum samples from healthy volunteers, individuals with premature coronary artery disease, individuals with hyperlipidaemia but without evidence of premature coronary artery disease, and also in elderly men and women who had hyperlipidaemia. Concentrations in individuals with premature coronary artery disease were the same as those of the healthy volunteers, while in both these groups they were lower than those found in hyperlipidaemic elderly men and women, and those found in hyperlipidaemic women aged 36-68 years. No association between raised lipoprotein(a) concentration and mortality as a result of premature coronary artery disease was demonstrated. Raised lipoprotein(a) levels found in the hyperlipidaemic individuals also suggested that it may not be an independent risk factor.     

Sex differences in coagulation and fibrinolysis in subjects with coronary artery disease

Women with coronary artery disease (CAD) have a prognosis at least as bad and possibly worse than men. Differences in classical risk factors do not fully account for these findings and there is evidence that circulating levels of haemostatic factors may predict CAD risk. In this study sex differences in haemostatic risk factors were examined in relation to coronary stenosis. 609 (420 men, 69%) subjects admitted for coronary angiography for suspected CAD were recruited. Levels of Factor VII:C (FVII:C), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF) were estimated in 296 subjects from one centre. Of these, women (n = 107) had higher levels of FVII:C (134% vs 117%, p < 0.0005), and fibrinogen (3.4 g/l vs 3.2 g/l p = 0.01) than men (n = 189) and these differences remained after adjusting for other covariates. In subjects with angiographically significant atheroma these differences in haemostatic factors (n = 50 for women vs n = 147 for men) were exaggerated, (FVII:C 139% vs 117, p < 0.0001, fibrinogen 3.7 g/l vs 3.3 g/l p = 0.003), PAI-1 (26.2 ng/ml vs 19.7 ng/ml, p = 0.02) with a trend towards higher levels of vWF in the women. Women with significant atheroma at angiography (n = 50) had higher levels of PAI-1 (25.0 ng/ml vs 13.4 ng/ml p < 0.0001) and vWF (1.25 IU/ml vs 1.06 IU/ml, p = 0.02) and a trend towards higher levels of both fibrinogen and FVII:C than women with normal or in significant coronary vessel disease (n = 57). Elevated circulating levels of PAI-1, vWF, fibrinogen and FVII:C in women with angiographically proven CAD may contribute to an adverse cardiovascular risk factor profile and the poorer prognosis in females than male patients with proven coronary artery disease.     

Decreased baroreflex sensitivity in patients with stable coronary artery disease is correlated with the severity of coronary narrowing

Although studies have shown that arterial baroreflex sensitivity (BRS) is decreased in patients with acute myocardial infarction, BRS changes in patients with stable coronary artery disease (CAD) have not been studied extensively. We assessed BRS by the phenylephrine method in 55 normotensive and nondiabetic patients with chronic effort angina, old myocardial infarction, or both. The control group consisted of 24 age-matched patients without coronary lesions. To identify factors that determine BRS in stable CAD, we performed multivariate analysis using age, sex, left ventricular ejection fraction, pulmonary artery wedge pressure, resting systolic blood pressure, resting heart rate, the number of stenotic coronary arteries, history of myocardial infarction, and the presence or absence of angina pectoris as variables. BRS was significantly lower in patients with CAD than in control subjects (5.9 +/- 2.9 vs 6.9 +/- 2.4 ms/mm Hg, p < 0.05). In patients with CAD, BRS was inversely correlated with age, the resting heart rate, and the number of stenotic coronary vessels (p < 0.001, p < 0.005, and p < 0.005, respectively), but was independent of other clinical parameters, including the history of myocardial infarction. In control subjects, BRS was significantly correlated only with age. These results indicate that BRS is decreased in patients with stable CAD, and this decrease is correlated with the extent and severity of coronary narrowing.     

Patients with carotid stenosis and clinical history negative for coronary disease. Usefulness of the ergometric test for the identification of ischemic myocardial disease

BACKGROUND: The purpose of this study was to evaluate, by Stress-Exercise Electrocardiography (SE), the presence of Coronary Artery Disease (CAD) in patients with asymptomatic or symptomatic carotid stenosis, who had no history of myocardial ischemia. MATERIALS, METHODS AND RESULTS: 133 patients with significant carotid stenosis (> = 50%) were consecutively studied according to an established vascular protocol. Of 92 patients with no history of CAD, 3 were excluded, 4 with bilateral carotid occlusion underwent an Echocardiography-Stress Test with Dipyridamole (ED) with negative result. 85 patients underwent a SE. The result was negative in 50 patients, positive in 21. In 14 patients the SE was uncertain so that they underwent an ED or stress thallium-201 myocardial scintigraphy with positive result in 2. No correlation between the degree of carotid stenosis and the positive SE in patients with significant carotid artery atherosclerosis was found. CONCLUSIONS: Our study demonstrates that about 25% of patients with significant asymptomatic and symptomatic carotid stenosis and no history of CAD had a latent myocardial ischemia and that the screening of these patients with SE is easy, inexpensive and safe and allow us to detect those who need a more active treatment.     

Parasympathetic activity is a major modulator of the circadian variability of heart rate in healthy subjects and in patients with coronary artery disease or diabetes mellitus

Autonomic heart rate control was assessed by power spectral analysis of heart rate variability in 24-hour ambulatory electrocardiographic recordings from 23 healthy subjects, 14 patients with coronary artery disease without cardiac dysfunction, and 14 patients with diabetes mellitus. The log value of the ratio of the low-frequency component (LF = 0.04 to 0.15 Hz) to the high-frequency component (HF = 0.15 to 0.5 Hz) and logHF were employed as indexes of sympathetic and parasympathetic activity, respectively. Diurnal and nocturnal logLF, logHF, and log(LF/HF) values were calculated for heart rates of 60, 70, and 80 beats/min. Intergroup differences among these three variables were not significant at any heart rate. Although a heart rate-related decrease in logHF was generally observed, the relationship between log(LF/HF) and heart rate was not consistent. The correlation between diurnal and nocturnal logHF values was significant at all three heart rates (r = 0.63, 0.87, and 0.59), whereas the diurnal log(LF/HF) was correlated with the nocturnal value only at 70 beats/min (r = 0.77). These results suggest that the heart rate during normal daily activities is a reliable indicator of parasympathetic tone, if not sympathetic tone, in healthy subjects and patients with coronary artery disease or diabetes mellitus.     

Is coronary spasmodicity unchangeable?: a study with acetylcholine or ergonovine in patients with ischemic heart disease

In a prospective study we investigated the results of 18 patients with Kienb?ck's disease stage II as defined by Decoulx, treated with transposition of the pedicled pisiform. In eight cases of minus variance of the ulna, a radius shortening osteotomy was performed. There was an average follow-up of 30 months, X-ray investigations were done every six months after operation. 17 patients had less pain, 14 patients showed an improved range of motion of 30 degrees. Magnetic resonance imaging proved vitalizing of the pisiforme in 16 cases.     

Reduced adipocyte insulin sensitivity in Caucasian and Asian subjects with coronary heart disease

The association between insulin resistance and coronary heart disease (CHD) is strong in the British Indian-Asian population. Adipocyte metabolism may contribute to both insulin resistance and CHD. We examined insulin-stimulated glucose uptake in adipocytes and in vivo insulin sensitivity using the fasting insulin resistance index (FIRI) in 60 subjects (45 Caucasian and 15 Asian) with CHD and 30 Caucasian subjects without CHD. In 25 CHD subjects (18 Caucasian and 7 Asian), the relationship between adipocyte insulin sensitivity and non-esterified fatty acid (NEFA) suppression to oral glucose was examined. Compared with controls, the CHD subjects had higher values of fasting insulin [51 (46 to 54) pmol l(-1) vs 36 (31 to 41) pmol l(-1) p< 0.01] and FIRI [1.65 (1.5 to 1.79) vs 1.06 (0.89 to 1.23), p < 0.01]. Among the CHD subjects, the Asians had higher values than Caucasian [insulin 58 (48 to 67) pmol l(-1) vs 48 (44 to 53) pmol l(-1) p < 0.01, FIRI 1.89 (1.44 to 2.13) vs 1.62 (1.4 to 1.79), p< 0.01)]. Insulin-stimulated glucose uptake in adipocytes was lower in the CHD than control subjects [56 (50 to 62) vs 115 (75 to 132) attomol min(-1).mm2, p < 0.05], being most reduced among the Asians. It was positively correlated with postprandial NEFA suppression and negatively with insulin release. In conclusion, abnormalities of adipocyte function and insulin sensitivity occur in CHD and may contribute to its aetiology.     

Association of increased QT dispersion with coronary atherosclerosis in patients with aortic stenosis

The structure of UCH9, which is a novel antitumor agent, was determined by spectroscopic methods. UCH9 consists of an aglycone and five 2,6-dideoxy sugars (three D-olivoses, one 4-O-methyl-D-olivose and one D-oliose). Four of the five sugars are sequentially connected through a beta 1-->3 linkage (olivose-1-->3-4-O-methyl-olivose-1-->3-oliose-1-->3-+ ++olivose). On the basis of the results of spectroscopic analysis, it was found that UCH9 belongs to the aureolic acid family of antibiotics. The structure of UCH9 is unique in that mono- and tetrasaccharide moieties, and a long hydrophobic side chain (sec-butyl group) are attached to the aglycone, while di- and trisaccharide moieties and a methyl or a hydrogen are attached in the case of the known aureolic acid analogs. It is known that aureolic acid analogs from a dimer in the presence of Mg2+. NMR, FAB-MS and atomic absorption analysis revealed that UCH9 isolated from Streptomyces also forms a dimer, containing one equivalent molar Mg2+.