High Risk Of Cardiovascular Complications Research Articles

The effect of leptin on Na +-H + antiport (NHE 1) activity of obese and normal subjects erythrocytes

Obesity is currently considered as a chronic metabolic disease, associated with a high risk of cardiovascular complications. Leptin, an adipocyte-derived hormone has a variety target cells influencing a wide range of processes. Possible counteractions of hyperleptinaemia are currently investigated. The Na +-H + exchanger (NHE 1) is involved in multiple cellular functions and its activation has been related to hypertension and obesity. NHE 1 is present on erythrocytes and can be stimulated by various hormones. Erythrocytes have on their surface a variety of receptors with mostly unknown function. In the present paper, the effect of leptin on erythrocytes NHE 1 activity has been investigated. For this reason, the intracellular pH and sodium influxes were measured before and after addition of leptin in erythrocyte suspensions from normal and obese individuals. Amiloride, a specific NHE 1 inhibitor, and staurosporine a protein kinase C inhibitor were used to inhibit erythrocyte NHE 1. For the binding study leptin was labeled with fluorescein isothiocyanate (FITC) and the binding on erythrocytes was estimated by Scatchard analysis. NHE 1 activity increased in the presence of leptin but significantly less in the obese than in the control group. Furthermore the concentrations of leptin binding sites on the surface of erythrocytes were lower in erythrocytes drawn from obese individuals than in erythrocytes drawn from normal subjects. Since NHE 1 activity has been associated with insulin resistance and hypertension, the activation of this antiport by leptin may represent a link between adipose tissue hypertrophy and cardiovascular complications of obesity.

Variability of diurnal changes in ambulatory blood pressure and nocturnal dipping status in untreated hypertensive and normotensive subjects

An absent or diminished blood pressure (BP) fall during sleep (so-called “nondipping”) has been associated with a higher risk of cardiovascular complications, but the long-term reproducibility of dipper status and the relationship between diurnal changes in BP and perceived sleep quality have not been previously documented in untreated hypertensive patients. Ambulatory BP (ABP) and dipping status were examined in 79 subjects (69 hypertensives and 10 normotensives) at 0, 6, and 12 months. Fifty-six percent of subjects had no change in their dipping status, the majority (53%) dipping normally on all three occasions. However, 44% of patients had variable dipping status, and normal nighttime dipping in BP was observed more often when patients perceived their sleep quality to be good during the period of ABP recording. These results highlight significant intrasubject variability in the diurnal fluctuations in ABP and dipper status, which may in part reflect day-to-day variations in sleep disturbance during ABP monitoring. Classifying hypertensive patients into dippers or nondippers on the basis of a single ABP recording is unreliable and potentially misleading.

P wave signal-averaged electrocardiogram as a new marker for atrial tachyarrhythmias in postoperative Fontan patients

OBJECTIVESThis study was undertaken to determine the potential role of P wave signal-averaged electrocardiogram (PSAECG) for risk assessment of atrial tachyarrhythmias (ATs) in patients after Fontan operation.BACKGROUNDOnset of atrial flutter/fibrillation (AFF) in patients who have undergone Fontan operation for univentricular hearts constitutes an unfavorable clinical event associated with a high risk of cardiovascular complications. There is no data available on PSAECG in postoperative Fontan patients to predict potential susceptibility to ATs.METHODSTwenty-four post-Fontan patients and 15 age-matched healthy subjects were prospectively studied with PSAECG, and the following measurements were made: filtered P wave duration (FPWD), P wave vector integrals (PINTs), root-mean-square voltage for the initial 30 ms (RMSi30), and duration of persistent amplitude signals <4 μV from the beginning of the P wave (Di4).RESULTSThe FPWDs were significantly longer in the study group patients with ATs when compared with the study group patients without ATs (p < 0.01) and compared with the controls (p < 0.001). An FPWD cut point of 135 ms resulted in a sensitivity of 71% and a specificity of 81% in differentiating patients with ATs from patients without ATs among the postoperative Fontan patients. The PINT was significantly greater in Fontan patients with AFF and also without AFF when compared with controls (p < 0.01, p < 0.05, respectively). The RMSi30 and the Di4 were not significantly different between study and control groups.CONCLUSIONSSignal-averaged P wave duration is significantly prolonged in postoperative Fontan patients. A prolonged signal-averaged P wave duration may be an effective noninvasive marker to predict risk of development of ATs in this patient group.

Excellent outcome of renal transplantation in patients with Fabry's disease.

Fabry's disease is an X-linked error of glycosphingolipid metabolism. Clinical manifestations of the disease are secondary to accumulation of glycosphingolipids in various tissues. Renal failure and vascular complications are common. There are conflicting reports regarding the outcomes of patients with Fabry's disease after renal transplantation. We reviewed the United States Renal Data System Registry database from 1988 and 1998, and found 93 patients with Fabry's disease who had received a renal transplant. Case-matched patients were identified to serve as controls. Patients with Fabry's disease demonstrated equivalent 5-year patient and graft survival, compared with controls (83% and 75%, respectively, for those with Fabry's disease vs. 82% and 67% for controls). Despite their high risk for cardiovascular complications, patients with Fabry's disease have excellent outcomes after renal transplantation.

Dietary and other non-pharmacological treatments in patients with drug-treated hypertension and control subjects.

To study the nutrient intakes and other lifestyle patterns of drug-treated hypertensives and control subjects. A cross-sectional population-based epidemiological study. The participating study subjects visited the research laboratory of the Department of Internal Medicine of the University of Oulu, Oulu, Finland. A total of 1045 Finnish men and women aged 40-60 years, of whom 716 (69%) completed 7-day food records. Intakes of energy, protein, total fat, saturated, monounsaturated and polyunsaturated fatty acids, carbohydrate, alcohol, fibre, calcium, magnesium, potassium and sodium were assessed from 7-day food records. The study also included measurements of blood pressure, blood glucose and plasma lipids, and anthropometric variables. Information about alcohol consumption, smoking habits and physical activity was collected by interviewing. Obesity was common amongst the hypertensive subjects, whose body mass indices were significantly higher than those of the control subjects. Only minor differences existed in the energy intake levels and nutrient intakes of the hypertensive and control cohorts, but the control subjects performed more physical activity than the hypertensive subjects. The dietary recommendations concerning the intakes of total and saturated fats, carbohydrate and fibre were poorly met by both the hypertensive and the control subjects. Alcohol consumption was high amongst the hypertensive men, especially amongst the smokers. Non-pharmacological treatment, including dietary management, of hypertensive patients at high risk for cardiovascular complications seems still to be inadequate. Additional well-focused efforts are needed to intensify the dietary treatment as well as to reduce alcohol consumption and smoking amongst hypertensives.

Echocardiographic definition of left ventricular hypertrophy in the hypertensive: which method of indexation of left ventricular mass?

It has been suggested that hypertensives at high risk of cardiovascular complications can be identified on the basis of their left ventricular mass as determined echographically. However, there is as yet a lack of consensus on the mode of indexation (body surface area, height, height 2.7) of left ventricular mass (LVM), and on the cut-off values for definition of left ventricular hypertrophy (LVH). The main objective of this study is to test the influence of the different modes of indexation for LVM on the prevalence of LVH in a population of never treated hypertensive patients on the basis of cut-offs for LVM based upon its relationship with ambulatory blood pressure (BP) measurement. A population of 363 untreated hypertensives was investigated using a standardised procedure. The men and women were analysed separately. We studied the relationship between mean daytime ambulatory systolic BP and LVM and calculated the LVM cut-off for a BP of 135 mm Hg using three different methods of indexation. On the basis of these criteria, the population was divided into those with and those without LVH. The prevalence of LVH was found to be higher when LVM was indexed to height2.7 (50.4%) or height (50.1%). Prevalence was lowest when LVM was indexed to body surface area (48.2%), which tended to minimise the hypertrophy in obese individuals. Only indexation by height 2.7 fully compensates for relationships between height and ventricular mass in this population. Indexing LVM to height 2.7 thus appeared to give a more sensitive estimate of LVH by eliminating the influence of growth. Cut-offs of 47 g/m2.7 in women and 53 g/m2.7 in men corresponded to a cardiovascular risk indicated by a daytime systolic BP >/=135 mm Hg.

Cardiac troponin T as a marker for myocardial ischemia in patients seen at the emergency department for acute chest pain

Background Identification of patients with acute chest pain at high risk for cardiovascular complications is a common and difficult challenge for clinicians and must be based initially on data from the history, physical examination, electrocardiogram, and chest radiograph. Some data suggest that elevations in cardiac troponin T (cTnT) may be useful for detection of less severe degrees of myocardial injury that may occur in some patients with unstable angina. Therefore we designed a prospective follow-up study to assess the diagnostic performance and prognostic value of cTnT in a population of patients presenting to the emergency department with acute chest pain. Methods The patient population included all 1477 admitted patients aged 30 years or more who presented to the emergency department of an urban teaching hospital from October 1992, through February 1994, with a chief symptom of acute chest pain not explained by trauma or chest radiograph abnormalities. The 1303 patients (88%) who had 2 or more measurements of cTnT during the first 24 hours after presentation comprised the final study population. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operator characteristics curve (ROC) were determined for cTnT and creatine kinase-MB (CK-MB) (measured using activity and mass assays) data from the first 24 hours after admission for the outcomes of acute myocardial infarction (AMI) and major cardiac events during the first 72 hours of hospitalization. Results The sensitivity and specificity of cTnT (threshold of 0.1 ng/mL) for detecting AMI during the first 24 hours after presentation were 99% and 86%, respectively. The CK-MB activity and mass assays had diagnostic performance for detecting AMI similar to cTnT. Among patients who did not meet study criteria for AMI, cTnT was elevated during the first 24 hours in 31% of patients who had major complications, compared with a 17% rate for the CK-MB activity assay and a 3% rate for the CK-MB mass assay. In these patients, the cTnT assay had superior diagnostic performance compared with the CK-MB mass assay as a marker for cardiac complications as assessed with ROC analysis ( P < .0004). Conclusions In a heterogeneous population of patients seen in the emergency department with acute chest pain, cTnT was similar to CK-MB (activity and mass assays) for detection of AMI and superior to the CK-MB mass assay as a marker for major cardiac events early in the hospital course among those who were ruled out for an AMI. Further study is required to determine how this assay can be used to provide more appropriate, cost-effective care. (Am Heart J 1999;137:1137-44.)

Effect of intensive glycaemic control on fibrinogen plasma concentrations in patients with Type II diabetes mellitus. Relation with beta-fibrinogen genotype.

Recent studies show that in diabetic subjects an increase of plasma fibrinogen concentration is associated with a high risk of cardiovascular complications. Environmental and genetic factors contribute to the plasma fibrinogen concentration. Several studies indicate a relation between the polymorphism in the 5' region of the beta-fibrinogen gene and plasma protein concentrations and in diabetes the possible influence of hyperglycaemia on fibrinogen is still debated. In this study we investigated these relations. Hind III polymorphism was evaluated by a polymerase chain reaction-technique. On the basis of the observed allelic combination of fibrinogen beta-gene polymorphism and the existence of poor metabolic control (glycated haemoglobin > or = 7.5%), 50 Type II diabetic patients were selected. They were divided into three groups according to their beta-gene polymorphism (alpha1alpha1: n = 20, alpha1alpha2: n = 15, alpha2alpha2: n = 15) and then intensive insulin therapy was started. After 3 months of intensive treatment, the improvement in glycaemic control was equivalent, in terms of glycated haemoglobin, in all the three groups. A fibrinogen reduction was observed in alpha1alpha2 and alpha2alpha2 but not in alpha1alpha1 subjects. These results underline a possible relation between fibrinogen genotypes and glycaemic control in determining plasma fibrinogen concentrations in diabetic patients.

Exacerbation of Atherosclerosis by Hypertension: Potential Mechanisms and Clinical Implications

I I with interest the comprehensive review by Chobanian and Alexander¹on potential mechanisms and clinical implications of the development of atherosclerosis in patients with hypertension. A further mechanism for the "exacerbation of atherosclerosis" in patients with hypertension that was not addressed in an otherwise excellent review is the prothrombotic (or thrombogenic) state in hypertension. The process of atherosclerosis (atherogenesis) is closely related to thrombogenesis, and accumulated evidence does suggest that patients with hypertension demonstrate rheological and coagulation abnormalities that are indicative of a prothrombotic or hypercoagulable state.^2-5Such abnormalities are thought to explain why, despite the arterial tree being exposed to high pressures, the complications associated with hypertension (such as heart attacks and strokes) are paradoxically thrombotic rather than hemorrhagic.²Hypertensive patients with left ventricular hypertrophy, who are at particularly high risk for cardiovascular complications, exhibit additional abnormalities of clotting factors that have been related to

Signal-averaged P-wave duration and risk of paroxysmal atrial fibrillation in hyperthyroidism

The onset of atrial fibrillation (AF) in hyperthyroid patients constitutes an unfavorable clinical event associated with high risk of cardiovascular complications, occurring in approximately one fifth of patients. Therefore, it is advantageous to define noninvasive markers that may identify patients at risk. The high-resolution, signal-averaged electrocardiogram was used to evaluate the relation between P-wave duration and occurrence of paroxysmal AF in a group of 50 patients with hyperthyroidism, of whom 24 had a history of paroxysmal AF and 26 did not. Filtered signal-averaged P-wave duration was measured over an average of 300 beats/patient while in sinus rhythm, both at the time of first diagnosis of hypermyroidism and after restoration of eutnyroidism by medical treatment. The 24 patients with paroxysmal AF had significantly greater P-wave duration than the 26 patients without it (135 ± 7 vs 124 ± 9 ms; p = 0.001). A P-wave duration cutoff value of 130 ms held specificity, sensitivity, and positive predictive accuracy values of 79%, 85%, and 83%, respectively. Of several variables, multivariate analysis showed P-wave duration to be the only independent variable significantly associated with the occurrence of paroxysmal AF. Thus, the high-resolution signal-averaged electrocardiogram may be a useful noninvasive clinical tool for the identification of electrical instability associated with paroxysmal AF in hyperthyroid patients.

1013-109 Effect of Picotamide in Preventing Cardiovascular Events in 438 Diabetic Patients: Results of a Multi-Centre, Placebo Controlled, 18-Month Study

In the A.D.E.P (Atherosclerotic Disease Evolution by Picotamide) study 2,304 patients with peripheral obstructive arterial disease (POAD) were recruited for a double blind 18-month multi-centre trial comparing picotamide (300 mg t.i.d.), an antiplatelet drug which inhibits thromboxane A2 (TxA2) synthase and antagonizes TxA2 receptor, and placebo. In the study population as a whole, 151 events (13.1%) occurred on placebo and 122 (10.6%) on picotamide, with a relative risk reduction of 19%, (p = 0.056, Logrank test, intention to treat analysis). The effect of picotamide was assessed in the A.D.E.P subgroup of diabetic patients, in order to test if the drug was still effective in patients at higher risk of cardiovascular complications. Diabetic patients were 438 (230 on picotamide and 208 on placebo). Most of them were male (80%), with a mean age of 64 years (min 40, max 75). Six per cent were insulin-dependent. The main risk factors (smoking, hypertension, previous vascular surgery, ankle/arm pressure ratio, WBC count and fibrinogen) were similarly distributed in the two groups. Diabetic POAD patients on placebo suffered from a total of 33 cardiovascular events (12 major and 21 minor) (15.9%), whereas those on picotamide suffered from a total of 20 events (6 major and 14 minor) (8.7%) (relative reduction of risk: 45.2%, p = 0.022 at Logrank test, intention to treat analysis). Both major and minor events occurred more frequently in the placebo than in the picotamide group. The overall incidence of major events was 5.8% on placebo and 2.6% on picotamide (relative risk reduction of 59.8%). Death occurred in 6 patients on placebo (2.9%) and in 3 on picotamide (1.3%). Non fatal major events (stroke, myocardial infarction and amputation) were 6 on placebo and 3 on picotamide. Minor events were 10.1% on placebo and 6.1% on picotamide (relative risk reduction of 39.8%). Adverse reaction, mainly gastrointestinal, occurred in 16% of patients, regardless of the treatment. In conclusion, this analysis indicates that Picotamide significantly reduces cardiovascular events in diabetic POAD patients, suggesting its potential use in patients at high risk of atherosclerotic progression.

Effect of picotamide on the clinical progression of peripheral vascular disease. A double-blind placebo-controlled study. The ADEP Group.

Patients with peripheral vascular disease (PVD) undergo a clinical course that can be complicated by cardiovascular events occurring in several areas of the circulation. In the present study we investigated the ability of picotamide, a substance that inhibits platelet thromboxane A2 (TxA2) synthase and antagonizes TxA2 receptors, to reduce cardiovascular complications in PVD patients. The study was double blind and placebo controlled. After a 1-month run-in period, 2,304 patients were randomly allocated to either placebo or picotamide (300 mg t.i.d.) and followed for 18 months. Major and minor events were analyzed. Results of an "intention-to-treat analysis" were that patients on picotamide suffered 45 major events (3.9%) and 77 minor events (6.7%), whereas those taking placebo suffered 52 major (4.5%) and 99 minor events (8.6%). There was borderline statistical difference between the two groups with respect to the sum of the major and minor events (risk reduction, 18.9%; p = 0.056, log-rank test). Results of an "on-treatment" analysis were that patients on picotamide suffered 40 major (3.8%) and 66 minor events (6.3%), whereas those taking placebo suffered 45 major (4.2%) and 95 minor events (8.9%). The sum of both major and minor events was 106 (10.1%) in the picotamide group and 140 (13.1%) in the placebo group. This difference was significant (risk reduction, 23%; p = 0.029, log-rank test). The results of this study indicate that picotamide reduces cardiovascular complications in PVD patients. The apparently low effect of this drug in reducing major events suggests that further studies be made with picotamide in PVD patients who are at high risk of cardiovascular complications so as to further assess its clinical efficacy.

The effect of low-dose oral contraceptives on lipids and lipoproteins in two at-risk populations: Young female smokers and older premenopausal women

Young women who smoke and women over age 35 are considered to be at high risk for cardiovascular complications associated with oral contraceptive use. This study evaluated the effects of low-dose oral contraceptives on lipid and lipoprotein concentrations in 45 high-risk patients before, during, and after 6 months of treatment. Neither group showed a significant change from baseline in cholesterol, HDL cholesterol, LDL cholesterol or cholesterol ratios. Triglycerides increased and HDL 2a levels decreased significantly in both groups but returned to baseline after treatment was discontinued, with the largest changes in both triglycerides and HDL 2a levels occurring at 1 month. The change in triglyceride and HDL 2a blood levels were within the laboratories' reference range. The lipid profile of these patients, therefore, was not worsened significantly through 6 months of oral contraceptive use. The young women who smoked did have consistently lowered levels of HDL cholesterol and its HDL 2a subfraction when compared to their elder non-smoking cohort.

Influence of cardiovascular diseases upon the results of the cardiovascular reflex tests in diabetic and nondiabetic subjects

Cardiovascular reflex tests are used to assess cardiac autonomic neuropathy in diabetes mellitus. Cardiovascular diseases (CVD) are known to alter baroreflex mechanisms. Diabetic patients are at a high risk for cardiovascular complications. In order to prove whether cardiovascular diseases reduce the diagnostic value of the cardiovascular reflex tests in diabetic autonomic neuropathy unselected groups of 274 nondiabetic and 103 diabetic patients were studied: E/I, 30/15, and Valsalva ratios, sustained handgrip test and blood pressure response to standing. Both groups were subdivided into young (less than or equal to 45 years) and older (greater than 45 years) patients and into subjects with and without CVD. In young nondiabetic patients with CVD, E/I and Valsalva ratios were significantly lower than in those without CVD. In young diabetic patients with CVD, only E/I ratios were significantly reduced compared to those without CVD. The tests reflecting sympathetic nerve function did not differ between patients with and without CVD, neither in the nondiabetic nor in the diabetic subjects. In the older nondiabetic and diabetic patients, cardiovascular reflexes were generally impaired, but did not show any difference between subjects with and without CVD. In young diabetic patients suffering from CVD, the diagnostic value of cardiovascular reflex tests is reduced as far as cardiac autonomic neuropathy is concerned. In older patients, the tests are not suitable for the diagnosis of diabetic autonomic neuropathy. More specific methods are required.

Tobacco Use by Children and Adolescents

Cigarette smoking is the chief single avoidable cause of death in our society and the most important health issue of our time.1 Despite increased public awareness of the long-term morbidity associated with the initiation of cigarette smoking during childhood and adolescence, the 1979 US Surgeon General's report on the health consequences of smoking estimated that 6 million teenagers smoke, and there are another 100,000 youngsters less than 13 years of age who smoke.2 In 1979, the National Institute of Education reported a fivefold increase in the number of smokers between junior high school- and senior high school-aged students.3 In 1983, Johnston et al4 found that 21% of high school seniors were regular daily smokers. Although there has been a general decline of cigarette smoking among male adolescents, there has been no parallel decline in the rate of cigarette smoking among young women, particularly those 17 and 18 years of age (J. A. Califano, Jr, unpublished remarks, 1968, 1974, 1979). Young women who use oral contraceptives are at higher risk of cardiovascular complications if they smoke. Among women who smoke during pregnancy, there is increased risk of poor fetal growth, spontaneous abortion, fetal death, and neonatal death.5,6 In addition to the use of cigarettes, the use of "smokeless tobacco," eg, chewing tobacco and snuff, is becoming more common among young people, particularly rural youth. It is estimated that between 10% and 20% of high school students use smokeless tobacco.7 Its use has been associated with leukoplakia, oral cancer, tooth abrasion, and loss of teeth.8