Troponin I and echocardiography in patients with systemic sclerosis and matched population controls.

OBJECTIVES: Cardiac manifestations in systemic sclerosis (SSc) are associated with poor prognosis. Few studies have investigated cardiac troponins in SSc. We studied the relationships between echocardiographic abnormalities, cardiac biomarkers, and disease manifestations in a population-based cohort of patients with SSc and controls. METHOD: The study comprised 110 patients with SSc and 105 age- and sex-matched population-based controls. We examined ventricular function, heart valves, and estimated pulmonary arterial pressure (ePAP) by echocardiography in all participants. Disease characteristics, manifest ischaemic heart disease (IHD), and measurements of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) were tabulated. RESULTS: NT-proBNP and hs-cTnI levels were higher in SSc patients than controls. Both NT-proBNP and hs-cTnI were associated with the presence of echocardiographic abnormalities. Forty-four SSc patients and 23 control subjects had abnormal echocardiograms (p = 0.002). As a group, SSc patients had lower (but normal) left ventricular ejection fraction (LVEF, p = 0.02), more regional hypokinesia (p = 0.02), and more valve regurgitations (p = 0.01) than controls. Thirteen patients and four controls had manifest IHD. Decreased right ventricular (RV) function (n = 7) and elevated ePAP (n = 15) were exclusively detected among SSc patients. CONCLUSIONS: Both NTproBNP and hs-cTnI were associated with echocardiographic abnormalities, which were more prevalent in SSc patients than in controls. Our results thus suggest that hs-cTnI could be a potential cardiac biomarker in SSc. Low RV function and signs of pulmonary hypertension (PH) were uniquely found in the SSc group. SSc patients had more valve regurgitation than controls, an observation that warrants more clinical attention.

Electrocardiography in 110 patients with systemic sclerosis: a cross-sectional comparison with population-based controls.

OBJECTIVES: Patchy fibrosis of the myocardium is thought to cause conduction abnormalities in patients with systemic sclerosis (SSc). We compared the prevalence and type of rhythm/conduction disturbances in 74% of the SSc patients in Stockholm County and controls. METHOD: A total of 110 SSc patients (age 62 ± 12 years) fulfilling the American College of Rheumatology (ACR) criteria for SSc and 105 gender- and age-matched controls participated in this study. A 12-lead resting electrocardiogram (ECG) was performed in all participants. The first 49 patients and 42 controls also underwent a 22-24-h Holter ECG recording. Associations with disease subsets, autoantibodies, cardiovascular risk factors, and left ventricular ejection fraction (LVEF), as estimated by echocardiography, were investigated. RESULTS: Abnormal ECGs were found in 28% of patients and 17% of controls (p = 0.05). Atrioventricular (AV) and/or intraventricular (IV) conduction abnormalities were found in 15% of patients and 5% of controls (p < 0.01). Four patients, but no controls, had low anteroseptal R-wave/septal Q-wave patterns with narrow QRS complexes, simulating a septal wall infarction pattern. Patients had more abnormal Holter ECG recordings than controls (38% vs. 17%, p = 0.05). All participants with a normal resting ECG had an LVEF ≥ 50%. CONCLUSIONS: Although ECGs are inexpensive, commonly available screening tools, to detect arrhythmias, such as frequent ventricular extrasystoles (VES), Holter tracings should be performed. The frequencies of AV and/or IV conduction abnormalities and septal Q waves/low R waves have not changed since 1985. The unmet need of anti-fibrotic treatment in SSc is underscored by these findings.

Dyslipidaemia and lipoprotein pattern in systemic lupus erythematosus (SLE) and SLE-related cardiovascular disease.

OBJECTIVE: This study focused on lipoprotein composition and properties in systemic lupus erythematosus (SLE). METHODS: The size distribution of plasma lipoproteins was studied by nuclear magnetic resonance (NMR). Cholesteryl ester transfer protein (CETP) activity was determined by enzyme-linked immunosorbent assay (ELISA). The affinity of low density lipoprotein (LDL) for proteoglycans was assayed. Twenty-six women (aged 52+/-8.2 years) with SLE and a history of cardiovascular disease (CVD) (SLE cases) were compared with 26 age-matched women with SLE and without CVD (SLE controls) and 26 age-matched population-based control women (controls). RESULTS: Very low density lipoprotein (VLDL) particles (nmol/L) were more prevalent among SLE cases than SLE controls (0.039) and tended to be more common in SLE cases than in controls (p = 0.073). By contrast, high density lipoprotein (HDL) particles (nmol/L) were more prevalent among controls than SLE cases (p = 0.024) whereas the number of LDL particles (nmol/L) did not differ significantly. Small dense (sd)LDL (nmol/L) were more common in controls and tended to be more common in SLE cases than in SLE controls (p = 0.036 and 0.086, respectively). Small high density lipoproteins (sHDL) (nmol/L) were more prevalent in controls than in SLE controls and SLE cases (p = 0.002 and p<0.001, respectively). VLDL or LDL size (nm) did not differ significantly between groups (data not shown) whereas HDL size (nm) was increased among SLE controls as compared to controls (p = 0.024) and tended to be increased among SLE cases as compared to controls (p = 0.070). The affinity of LDL for proteoglycans or CETP activity did not differ between groups (data not shown). CONCLUSIONS: sdLDL was not increased and SLE cases and SLE controls had decreased levels of sHDL. VLDL differentiates between SLE cases and SLE controls. The lipid pattern in SLE-related CVD was thus not similar to the pattern seen in diabetes or in CVD in general.

Endothelial function and markers of endothelial activation in relation to cardiovascular disease in systemic lupus erythematosus.

OBJECTIVE: Cardiovascular disease (CVD) is common in patients with systemic lupus erythematosus (SLE) although it is not clear whether an increased risk of CVD is a general feature of SLE or whether it applies only to a subgroup of patients. Our objective was to evaluate endothelial function and markers of endothelial activation in relation to CVD in SLE. METHODS: Twenty-six women with SLE and previous CVD (SLE/CVD cases, defined as objectively verified angina pectoris, myocardial infarction, cerebral infarction, or intermittent claudication; 52+/-8.2 years) were compared with age-matched SLE women without CVD (SLE controls) and population control women. Flow-mediated dilatation (FMD) of the brachial artery after reactive hyperaemia and nitroglycerin-mediated dilatation (NMD) after sublingual nitroglycerin administration were determined by ultrasound. Soluble thrombomodulin (sTM) and soluble vascular cellular adhesion molecule-1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: FMD and NMD levels did not differ between SLE controls and population controls. In SLE cases FMD and NMD were not assessed because of interference with nitro-related medication. sVCAM-1 discriminated between SLE cases, SLE controls, and population controls (ng/mL; 814+/-221 vs. 545+/-214 vs. 401+/-189, p<0.01), whereas sTM (ng/mL; 5.2+/-2.8 vs. 4.2+/-1.9 vs. 3.0+/-0.5) differed between both SLE groups and controls (p<0.05). CONCLUSION: In this study SLE women free of CVD had good endothelial function (FMD), a possible marker of protection from lupus-related CVD. In addition, high levels of sVCAM-1, associated with systemic tumour necrosis factor-alpha (TNFalpha) activity, were identified as a novel discriminator for SLE-related CVD. This supports our hypothesis that SLE patients with enhanced systemic TNFalpha activity are at high risk of developing CVD.

TNF-alpha: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease.

Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathophysiological processes of both SLE and CVD. This study focuses on the role of TNF-alpha and its soluble receptors in SLE-related CVD. In summary, 26 women (52 +/- 8.2 years) with SLE and a history of CVD (SLE cases) we compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched population-based control women (population controls). Plasma concentrations of circulating TNF-alpha, TNF-alpha receptor 1 (sTNFR1) and TNF-a receptor 2 (sTNFR2) were determined by ELISA. TNF-alpha, sTNFR1 and sTNFR2 were raised in SLE cases as compared to SLE controls (P = 0.009; P = 0.001; P = 0.001, respectively), and SLE controls had higher levels than population controls (P = 0.001; P = 0.02; P = 0.001, respectively). Exclusively in the SLE case group there was a striking positive correlation between TNF-alpha and plasma triglycerides (r = 0.57, P < 0.002), VLDL triglycerides (r = 0.54, P = 0.004) and VLDL cholesterol (r = 0.58, P = 0.002). Furthermore, TNF-alpha correlated with the waist-hip ratio but not with estimated insulin resistance. TNF-alpha may thus be a major factor in SLE-related CVD acting both by contributing to hypertriglyceridaemia and by promoting atherosclerosis-related inflammation. sTNFR1 and sTNFR2 are strongly associated with CVD in SLE but their exact roles in disease development remain to be elucidated.

Influence of glucose control, lipoproteins, and haemostasis function on brachial endothelial reactivity and carotid intima-media area, stiffness and diameter in Type 1 diabetes mellitus patients.

BACKGROUND: The objectives of this study were to determine the influence of glucose control on lipoprotein and haemostasis variables in Type 1 diabetes mellitus patients and to evaluate the global impact of these metabolic risk factors on brachial artery reactivity and carotid artery atherosclerosis, stiffness and diameter. DESIGN: Follow up of Type 1 diabetes patients randomized to insulin-intensive conventional treatment (ICT, n = 29) or insulin-standard treatment (ST, n = 25) in the Stockholm Diabetes Intervention Study (SDIS) more than 14 years ago. RESULTS: The intensive conventional treatment patients had lower glycosylated haemoglobin (HbA1c) compared with the ST patients, i.e. 7.01 (SD 0.51) vs. 8.31 (0.97), while concentrations of the lipoprotein and haemostasis variables analyzed were virtually similar. The carotid artery intima-media area was associated with high HbA1c, high serum (S)-cholesterol levels, and low high-density lipoprotein (HDL)-cholesterol levels. Carotid artery stiffness was associated with high systolic blood pressure, high HbA1c, high fibrinogen, and high HDL-cholesterol. Brachial artery endothelial reactivity was higher for women and those with low S-cholesterol. CONCLUSION: In patients with Type 1 diabetes, glucose control appeared to have no effect on either lipoproteins or haemostasis variable concentrations. Poor glucose control, and high levels of S-cholesterol, systolic blood pressure and plasma fibrinogen were associated with development of atherosclerosis, thus emphasising the importance of global risk factor control in patients with Type 1 diabetes mellitus.

Cardiac valvular abnormalities are frequent in systemic lupus erythematosus patients with manifest arterial disease.

The objective of this study was to study cardiac valve morphology and function and ventricular function in systemic lupus erythematosus (SLE) patients with and without co-existing cardiovascular disease (CVD) and in population controls. Twenty-six women (52 +/- 8.2 years) with SLE (SLE cases) and a history of CVD (angina pectoris, myocardial infarction, cerebral infarction or intermittent claudication) were compared with 26age-matched women with SLE but without manifest CVD (SLE controls) and 26 age-matched control women (population controls). Echocardiographywas performed to assess valvular abnormalities and manifestations of ischaemic heart disease. Thirteen of the 26 SLE cases but only one of the SLE controls and one of the population controls had cardiac valvular abnormalities. Three of the SLE cases had already undergone valve replacement and another had significant aortic insufficiency; the other nine had thickening of mainly mitral leaflets without hemodynamic significance. Among SLE cases, patients with valvular abnormalities had higher homocysteine (P < 0.001) and triglyceride (P = 0.02) concentrations than patients without valvular disease. In contrast atherosclerosis as determined by IMT, oxidized LDL as measured by the monoclonal antibody E06, autoantibodies against epitopes of OxLDL (aOxLDL) or phospholipids (aPL), disease duration or activity, or acute phase reactants did not differ between SLE cases with or without valvular abnormalities. Valvular abnormalities were not more common in SLE cases with stroke as compared to those with myocardial infarction, angina or claudication. In conclusion, valvular abnormalities are strongly associated with CVD in SLE. Raised levels of homocysteine and triglycerides characterize patients with cardiac valve abnormalities.

Risk factors for cardiovascular disease in systemic lupus erythematosus.

BACKGROUND: Cardiovascular disease (CVD) is overrepresented in patients with systemic lupus erythematosus (SLE). We determined the prevalence of traditional and nontraditional risk factors for CVD in SLE patients with and without CVD compared with controls. METHODS AND RESULTS: Twenty-six women (aged 52+/-8.2 years) with SLE and a history of CVD (SLE cases) were compared with 26 age-matched women with SLE but without manifest CVD (SLE controls) and 26 age-matched population-based control women (population controls). Common carotid intima-media thickness (IMT) was measured by B-mode ultrasound as a surrogate measure of atherosclerosis. SLE cases had increased IMT compared with SLE controls (P=0.03) and population controls (P=0.001), whereas IMT of SLE controls did not differ from population controls. SLE cases had raised plasma concentrations of circulating oxidized LDL (OxLDL; P=0.03), as measured by the monoclonal antibody EO6, and autoantibodies to epitopes of OxLDL (P<0.001); dyslipidemia with raised triglycerides (P<0.001) and lipoprotein(a) (P=0.002) and decreased HDL-cholesterol concentrations (P=0.03); raised alpha-1-antitrypsin (P=0.002), lupus anticoagulant (P=0.007), and homocysteine levels (P=0.03); more frequent osteoporosis (P=0.03); and a higher cumulative prednisolone dose (P=0.05) compared with SLE controls. Disease duration, smoking, blood pressure, body mass index, and diabetes mellitus did not differ significantly between the groups. CONCLUSIONS: alpha set of distinct CVD risk factors separate SLE cases from SLE controls and population controls. If confirmed in a prospective study, they could be used to identify SLE patients at high risk for CVD in order to optimize treatment.

Spontaneous delayed recovery of perfusion after thrombolyzed acute myocardial infarction: is it predictable before discharge?

In patients with thrombolyzed acute myocardial infarction, early assessment of the final infarct size is difficult because spontaneous recovery of perfusion and function of the left ventricle may be delayed. This study was undertaken to evaluate the ability of predischarge low-dose dobutamine echocardiography to predict late spontaneous recovery of perfusion assessed by single-photon emission computed tomography after acute myocardial infarction. We prospectively studied 53 consecutive patients with myocardial infarction treated with thrombolysis. Low-dose dobutamine echocardiography and resting (99m)Tc-sestamibi single-photon emission computed tomography (MIBI SPECT) were performed 4 +/- 2 days after infarction. A follow-up SPECT study was carried out in 45 patients after 6 months. Myocardial recovery was defined as a reduction of SPECT defect size by more than 10% at follow-up compared with the early study. In 25 of the 45 patients, the size of the left ventricular perfusion defect decreased significantly from 42% +/- 16% to 27% +/- 10% (group 1), whereas in the remaining 20 patients it showed no significant change (group 2). Predischarge low-dose dobutamine echocardiography showed a significant improvement in wall motion score index compared with baseline in group 1, from 1.62 +/- 0.28 to 1.41 +/- 0.24, P <.001, whereas in group 2 this index remained without significant change. Predischarge low-dose dobutamine echocardiography is an accurate tool for prediction of late recovery of myocardial perfusion after acute myocardial infarction treated with thrombolysis.

Gender difference in age-related changes in vascular function.

PURPOSE: We investigated whether, in a randomly selected population of 55-year-old men and women, there is a relationship between vascular function measured as flow-mediated (endothelium-dependent) and nitroglycerine-mediated (nonendothelium-dependent) dilatation of the brachial artery and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood-lipids and high blood pressure. The results are compared with those in a young healthy population of 35-year-olds. SUBJECTS: A total of 57 men (73% of the invited males) living in the community and 47 women (62% of the invited females) participated and were compared with a previously studied 35-year-old population (52 men and 56 women). METHODS: Basal brachial artery diameter was measured by high-frequency ultrasound methods. Endothelial function was measured as flow-mediated dilatation (FMD) in response to reactive hyperaemia. The nonendothelium-dependent vasodilatation was measured after administering sublingual nitroglycerine (NTG). RESULTS: Flow-mediated endothelium-dependent dilatation was similar in men and women being 3.1 +/- 2.5% (mean +/- SD) in men vs. 2.6 +/- 2.3% in women. FMD of the brachial artery was negatively correlated with vessel size in both men and women (P < 0.001). Men had larger brachial artery diameter than women (4.6 +/- 0.7 vs. 3.6 +/- 0.4 mm, P < 0.001). There was no difference in FMD or in NTG-induced dilatation in the women receiving oral oestrogen replacement therapy compared with those that did not. The women taking oral oestrogen had lower cholesterol than those not taking oral oestrogen (P=0.04). FMD was not correlated with any of the risk factors. NTG-induced vasodilatation was correlated with the body mass index (BMI) in men (P=0.01) and a combined risk factor score in women (P=0.04). There was a large increase in the number of subjects with cardiovascular risk factors in the 55-year-old men and women compared with the 35-year-olds. The distribution of risk factors was fairly equal amongst men and women. CONCLUSION: There are no correlations between any of the conventional cardiovascular risk factors and FMD in a population of 55-year-olds, but there is a high prevalence of risk factors in the 55-year-old age group. NTG-induced vasodilatation correlated with the BMI in men and a combined risk-factor score in women. FMD-induced vasodilatation is smaller in women at 55 years of age than at 35 years of age. FMD was similar in men at 35 and 55 years of age and in men and women at 55 years of age. The smaller FMD in women at 55 years of age, compared with at 35, could be due to postmenopausal hormonal changes.

Risk assessment in patients with acute myocardial infarction treated with thrombolytic therapy.

OBJECTIVE: Several noninvasive methods have prognostic information regarding mortality and new coronary events after an acute myocardial infarction (AMI). The practical for clinical decision-making in the immediate postmyocardial infarction (MI) period is, however, less evident. We investigated consecutive patients with AMI treated with thrombolysis to further clarify this issue. DESIGN: A total of 100 patients (27% women) aged 64 +/- 9 years (mean +/- SD) were studied. Risk assessment based on a clinical score system, myocardial perfusion scintigraphy single photon emission computed tomography (SPECT) at rest and during adenosine stress, echocardiography, radionuclide angiography, symptom-limited exercise stress test, and 24-h Holter ECG recording with ST-analysis and analysis of heart rate variability (HRV) were performed 5-8 days after hospital admission. Mortality, nonfatal reinfarction, and the need for revascularization were followed during 12 months. SETTING: A university hospital. RESULTS: A total of 6 patients died, seven had a nonfatal reinfarction, and 23 were revascularized. Inability to perform an exercise test (P = 0.004) and an ejection fraction (EF) < 40% (P = 0.002) were the only parameters separating those who died from the survivors. No method could predict a nonfatal reinfarction. Patients suffering either death or nonfatal reinfarction had a clinical risk assessment score 2 points higher (8.8 vs. 6.7, P = 0.05) than the group without such events. A positive symptom-limited exercise stress test (P = 0.027), ST-depressions on Holter ECG (P = 0.04), and reversibility on myocardial perfusion scintigraphy (P = 0.029) predicted the need for revascularization. CONCLUSION: Risk assessment based on clinical information, exercise stress testing, and an estimate of left ventricular function (e.g. via echocardiography) contribute with prognostic information in thrombolysed MI-patients. Additional noninvasive investigations such as adenosine-SPECT, analysis of HRV, and Holter-monitoring do not add to these commonly available tools in risk stratification of subjects at low to medium risk.

Myocardial viability in patients with thrombolyzed myocardial infarction: is it assessable by predischarge exercise electrocardiography test?

BACKGROUND: Most studies concerning exercise electrocardiography (ECG) testing after acute myocardial infarction (AMI) were carried out in the prethrombolytic era. ST-segment elevation in the infarction area during exercise has usually been interpreted as indicating the presence of dyskinesia as a result of extensive left ventricle damage. HYPOTHESIS: This study was undertaken to evaluate the contributions of exercise-induced ST-segment elevation and T-wave pseudonormalization to the assessment of myocardial viability in patients with thrombolyzed myocardial infarction (MI), compared with low-dose dobutamine echocardiography. METHODS: The study comprised 52 consecutive patients with AMI treated with thrombolysis. All patients underwent low-dose dobutamine echocardiography and symptom-limited exercise testing before discharge. RESULTS: Nineteen patients showed ST-segment elevation (Group 1), 9 showed isolated T-wave pseudonormalization (Group 2), and 24 patients did not exhibit either of these ST-T segment changes (Group 3). Low-dose dobutamine echocardiography revealed evidence of viability in 16 patients (84%) in Group I (p = 0.01), 5 (56%) in Group 2 (p = NS), and 11 patients (46%) in Group 3 (p = NS). CONCLUSION: Exercise-induced ST-segment elevation may contribute to the evaluation of myocardial viability in patients with AMI treated with thrombolysis. However, in the absence of exercise-induced ST-segment elevation, further noninvasive studies might be indicated to assess myocardial viability.

Physical training in Syndrome X: physical training counteracts deconditioning and pain in Syndrome X.

OBJECTIVES: The aim of this study was to evaluate the effects of exercise training and body-awareness training in female patients with Syndrome X. BACKGROUND: Patients with Syndrome X, defined as effort-induced angina pectoris, a positive exercise test and a normal coronary angiogram, suffer from a chronic pain disorder. We hypothesized that this disorder results in physical deconditioning with decreased exertional pain threshold. METHODS: Twenty-six patients were randomly assigned to two training groups (A, B) and a control group (C). Group A (n = 8) started, after baseline measurements, with eight weeks of body-awareness training followed by eight weeks of exercise training on a bicycle ergometer three times a week for 30 min at an intensity of 50% of peak work rate. Group B (n = 8) performed only eight weeks of exercise training. Group C (n = 10) acted as controls without any intervention whatsoever. The effects on exercise performance, hormonal secretion, vascular function, adenosine sensitivity and quality of life were evaluated. RESULTS: Body-awareness training did not change the pain response. The two training groups did not differ in effects of exercise training. Exercise capacity before training was below the gender- and age-matched reference range and improved by 34% with training to a level not different from the reference range. Onset of pain was delayed by 100% from 3 +/- 2 to 6 +/- 3 min (p < 0.05) while maximum pain did not change. Thus the pain-response-to-exercise curve was shifted to the right. Syndrome X patients showed a hypersensitivity to low-dose adenosine infusion compared to healthy age- and gender-matched controls (p < 0.0001) that did not change with exercise training. Endothelium-dependent blood flow increase was at baseline within reference range and tended to increase (p < 0.06) following training. In Group A the concentration of cortisol in urine decreased by 53% after body-awareness training (p < 0.05), and this change from baseline remained after physical exercise training (p < 0.05). A similar decrease occurred with only exercise training (Group B). CONCLUSIONS: Physical deconditioning with lower exertional threshold for pain is a prominent feature in Syndrome X. Physical training in Syndrome X results in an increased exercise capacity with lesser anginal pain. We suggest physical training as an effective treatment in Syndrome X.

Autonomic neuropathy--a complication less pronounced in patients with Type 1 diabetes mellitus who have lower blood glucose levels.

AIMS: Autonomic neuropathy is a serious diabetic complication, probably contributing to the death of many young people with Type 1 diabetes mellitus. It is often not diagnosed. METHODS: Patients with Type 1 diabetes from the Stockholm Diabetes Intervention Study were investigated with power spectral analysis (n = 88), heart rate and blood pressure reactions to tilting (n = 66), and heart rate variability during deep breathing (n = 70) a mean of 11.4 years after randomization to intensified conventional treatment (ICT) or standard treatment (ST), the treatment groups similar with regard to age, duration of diabetes and metabolic control at baseline (HbA1c 9.4 (1.3)%, mean (SD)). Blood glucose levels (mean of 29 HbA1c values) during the 10 years were lower in the patients from the ICT group (7.2 (0.6) vs. 8.3 (1.0)%, P = 0.001). RESULTS: Heart rate variability (HRV) in the high frequency range (P = 0.034), the expiration-inspiration ratio (P = 0.020), and the brake index during tilt (P = 0.044) were lower in the ST group, indicating more pronounced parasympathetic insufficiency. Systolic blood pressure fell by 10 (16) mmHg in the ST group, and by 2.5 (15) mmHg in the ICT group 8 min after rising from the supine to a 70 degrees upright position (P = 0.034). A decreased autonomic function was associated with age and higher HbA1c. CONCLUSION: Better autonomic nerve function is associated with lower HbA1c and lower age which were both the same in the intensively and the conventionally treatment groups at baseline. After a mean of 11.4 years autonomic function was better in the intensively treated group.

Carotid artery diameter correlates with risk factors for cardiovascular disease in a population of 55-year-old subjects.

BACKGROUND AND PURPOSE: We investigated whether, in a randomly selected population of 55-year-old men and women, there is a relationship between common carotid artery (CCA) diameter and intima-media (IM) thickness and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood lipids, and high blood pressure. METHODS: CCA diameter and IM thickness of the distal right and left CCAs were measured by high-frequency ultrasound methods. Fifty-seven men (73% of the invited men) and 47 women (62% of the invited women) participated. RESULTS: In the whole group the CCA diameter was correlated with gender (P<0.001), cholesterol (P=0.007), triglycerides (P<0.001), apoB (P<0.001), apoB/A-1 (P<0.001), systolic blood pressure (P=0. 001), and glucose (P=0.006). HDL was inversely correlated with mean CCA diameter (P=0.003). In men the CCA diameter was correlated with a combined risk factor score (P=0.005), systolic blood pressure (P=0. 011), platelet count (P=0.033), apoB (P=0.025), and occurrence of plaque (P=0.003). In women the CCA diameter was correlated with a combined risk factor score (P=0.010), systolic blood pressure (P=0. 033), body mass index (P<0.001), cholesterol (P=0.009), triglycerides (P=0.14), apoB (P=0.002), and apoB/A1 (P=0.003). IM thickness was correlated with systolic blood pressure (P<0.001). CONCLUSIONS: There are correlations between risk factors for cardiovascular disease and carotid artery diameter and IM thickness in both women and men in a population of 55-year-old subjects. The increased vessel diameter in subjects with cardiovascular risk factors may be a sign of attenuated vasoregulation, which could be an important factor during the development of atherosclerosis.

Prognostic value of symptom limited versus low level exercise stress test before discharge in patients with myocardial infarction treated with thrombolytics.

OBJECTIVE: To evaluate the benefits and risks of symptom limited exercise testing versus low level exercise testing soon after a thrombolytic treated acute myocardial infarction. DESIGN AND PATIENTS: 98 patients (71 men, 27 women), mean (SD) age 64 (9) years (range 45-75 years), were investigated 5-8 days after admittance to hospital. An ergometer cycle test was used, starting at 30 W with 10 W increments per minute. Each exercise test was interpreted at the symptom limited end point and a low level end point, which was defined as the point at which the patient rated exhaustion as 13 on the 6-20 point Borg scale for rating perceived exertion. SETTING: A university hospital. RESULTS: 75 of the 98 patients were able to perform a predischarge exercise test. Of the remaining 23 patients who could not perform an early exercise test (because of unstable angina, heart failure, or thrombus detected at echocardiography), five died or had a myocardial infarction and six underwent bypass surgery or percutaneous transluminal coronary angioplasty (PTCA) during a follow up period of one year. There were no complications related to the symptom limited exercise tests. The test results were positive in 15 patients at the low level end point and in 39 patients (p < 0.001) at the symptom limited end point. During a follow up period of one year, six of the 75 patients died or had a myocardial infarction. Two of these six patients had a positive low level exercise test and four had a positive symptom limited exercise test. Twenty three of the 75 patients who performed an exercise test had a cardiac event within one year (death, myocardial infarction, bypass surgery or PTCA); of these, 19 had a positive symptom limited exercise test and nine had a positive low level exercise test (p = 0.025). Four of the 36 patients with a negative symptom limited test suffered cardiac events within a year (two patients had a myocardial infarction and two had bypass surgery). CONCLUSION: Symptom limited exercise testing soon after thrombolytically treated myocardial infarction will identify more patients with exercise induced ST depression or chest pain than a low level test, and seems safe. A negative symptom limited test has a better negative predictive value (11% risk of an event within a year) than a negative low level (25% risk of an event within a year).

Preserved vascular reactivity in elderly male athletes.

The objective was to characterise function and morphology of the arterial wall in 9 elderly men (mean age 75 +/- 3.4 years) with a history of lifelong regular strenuous exercise. A control group of 11 healthy sedentary or moderately physically active men (74.5 +/- 2.7 years) was also studied. With increasing age atherosclerosis becomes more common and endothelium-dependent vasodilation reduced. The effects of training on endothelial function and atherosclerosis have not been studied previously in elderly subjects. High-frequency ultrasound was used to estimate vasodilatory function in the brachial artery. The endothelium-dependent (flow-mediated) and non-endothelium-dependent (nitroglycerine-induced) dilation of the brachial artery were measured. Stasis was used to induce reactive hyperaemia. The carotid arteries were scanned for plaques, intima-media thickness was measured in the common carotid arteries and arterial wall stiffness was calculated from pulsatile diameter changes in the right carotid artery in relation to blood pressure. The athletes' maximal oxygen uptake during treadmill exercise was 2.90 +/- 0.50 l or 41 +/- 7 ml.kg-1. The athletes' and the controls' maximal exercise capacity on a bicycle was 254 +/- 38 W and 148 +/- 19 W respectively (P < 0.001). The athletes' body mass index was 22.6 +/- 2.6 kg.m-2 and the controls' body mass index was 25.8 +/- 3.5 kg.m-2 (P = 0.037). Three of 9 athletes had plaques in either or both carotid bifurcations compared with 6 of 11 controls. The athletes had less stiff arteries and better vasodilatory capacity in the brachial artery during increased flow, and borderline significantly greater vasodilation after nitroglycerine. So, elderly athletes with a lifelong training history appear to have better vasodilatory capacity and less stiff arteries than healthy controls. Plaques in the carotid bifurcation were common in both athletes and controls.

Antiplasmin correlates to arterial reactivity in a healthy population of 35-year-old men and women.

OBJECTIVE: To study whether haemostasis function variables correlate with endothelial function and other vasomotion characteristics of the brachial artery in a randomly selected healthy population of 35-year-old men and women. DESIGN: Endothelial function was measured as flow mediated dilatation (FMD) of the brachial artery during reactive hyperaemia and the nonendothelial dependent dilatation after sublingual nitroglycerin (NTG) was administered. Haemostasis and fibrinolysis function were estimated by analysis of von Willebrand factor, plasminogen activator inhibitor-1, antiplasmin and fibrinogen. SETTING: A general medicine research centre and a university hospital. SUBJECTS: Randomly chosen men (n = 53) and women (n = 56). RESULTS: Univariate correlation analysis showed significant correlations between haemostasis factors, conventional risk factors for cardiovascular disease and indices of vasomotion of the brachial artery. In multivariate analysis, with haemostasis variables and conventional risk factors included, antiplasmin was the strongest explanatory variable for FMD. When antiplasmin was removed from the analysis, the r-value dropped from 0.46 to 0.35. Antiplasmin also correlated with NTG-induced dilatation (positively) and brachial diameter at rest (negatively), albeit less consistently. CONCLUSIONS: Antiplasmin correlates significantly and independently to FMD, reflecting endothelial function, and also to brachial artery diameter at rest and nitroglycerin-induced dilatation. In multivariate analysis these correlations of antiplasmin to arterial characteristics were stronger than for 'conventional' risk factors, such as smoking, blood pressure and serum cholesterol.

Decreased heart rate variability in patients with type 1 diabetes mellitus is related to arterial wall stiffness.

OBJECTIVE: Low heart rate variability (HRV) is, in several patient groups, related to poor prognosis. The underlying mechanisms are still unclear. The aim was to study if there is a relationship between HRV, which is a measure of baroreceptor function, and atherosclerosis. DESIGN: The relationship between heart rate variability and carotid arterial wall stiffness was studied in subjects with type 1 diabetes mellitus in which autonomic dysfunction and early atherosclerosis are common. HRV was assessed from power spectral analysis of 24-h Holter recordings and arterial wall stiffness was assessed from an ultrasound study of the right common carotid artery. SETTING: A university hospital. SUBJECTS: Fifty-nine patients (41 +/- 8 years) from the Stockholm Diabetes Intervention Study (SDIS) were investigated. These patients were randomized to intensified conventional treatment or standard treatment approximately 12 years before this study. RESULTS: Patients with stiffer arteries had lower HRV in all spectral bands (r = -0.32 to -0.40, P = 0.06-0.001). This relation remained on correcting for age. All spectral parameters of HRV correlated with the mean HbA1c from 10 years of study (r = -0.37 to -0.40, P = 0.004-0.001). CONCLUSIONS: In patients with type 1 diabetes mellitus, heart rate variability and arterial wall stiffness are related to each other. The results suggests that the autonomic nervous system could be a link between diabetes and vascular disease.