Cardiometabolic and immune factors associated with increased common carotid artery intima-media thickness and cardiovascular disease in patients with systemic lupus erythematosus.

BACKGROUND AND AIM: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear. METHODS AND RESULTS: Fifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4(+)HLA-DR(+) and CCR5(+) T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets. CONCLUSION: HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which 'classic' CV risk factors give a continuous contribution, together with immunological factors (CD4(+)HLA-DR(+) T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis.

Disulfiram enhances pharmacological activity of barbital and impairs its urinary elimination.

Disulfiram or diethyldithiocarbamate significantly enhanced the sleeping time induced by barbital in rats. At identical time intervals after rats were injected with barbital the concentration of barbital in the blood or brain of animals that had previously received disulfiram was significantly higher than the concentrations in the corresponding tissues of control animals. Urinary excretion of barbital was significantly reduced in disulfiram-treated animals.

Major racial differences in coronary constrictor response between japanese and caucasians with recent myocardial infarction.

BACKGROUND: Enhanced coronary vasomotion may contribute to acute coronary occlusion during the acute phase of myocardial infarction (AMI). Japanese have a higher incidence of variant angina than Caucasian patients, but racial differences in vasomotor reactivity early after AMI are controversial. METHODS AND RESULTS: The same team studied 15 Japanese and 19 Caucasian patients within 14 days of AMI by acetylcholine injection into non-infarct-related (NIRA) and infarct-related (IRA) coronary arteries followed by nitroglycerin. Incidence of vasodilation, vasoconstriction, spasm, and basal tone were assessed in proximal, middle, and distal segments after each drug bolus by quantitative angiography. Japanese patients had much lower cholesterol levels than Caucasians (183+/-59 versus 247+/-53 mg/dL, P<0.006) but showed a lower incidence of vasodilation (2% versus 9% of coronary segments) and a greater incidence of spasm after acetylcholine (47% versus 15% of arteries, P<0.00001). Incidence of spasm was higher in IRAs than in NIRAs in both populations (67% versus 39% and 23% versus 11%, respectively). Multivessel spasm was more common (64% versus 17%, P<0.02) and vasoconstriction of nonspastic segments was greater in Japanese patients (-23.4+/-14.9% versus -20.1+/-15.7%, P<0.02) in the presence of similar average basal coronary tone with respect to post-nitroglycerin dilation and of nonsignificant differences of coronary atherosclerotic score. CONCLUSIONS: Soon after AMI, Japanese patients exhibited a 3-fold-greater incidence of spasm and greater vasoconstriction of nonspastic segments after acetylcholine than Caucasians. The causes of such differences warrant further investigation because they may have relevant pathophysiological and therapeutic implications.

Assessment of residual tissue viability by exercise testing in recent myocardial infarction: comparison of the electrocardiogram and myocardial perfusion scintigraphy.

The assessment of residual myocardial viability in infarcted areas is relevant for subsequent management and prognosis but requires expensive technology. To evaluate the possibility that simple, easily obtainable clinical markers may detect the presence of within-infarct viable tissue, the significance of exercise-induced ST elevation occurring in leads exploring the area of a recent Q wave myocardial infarction was assessed. Twenty-five patients with recent (less than 6 months) myocardial infarction were studied. All had angiographically documented coronary artery disease, diagnostic Q waves (n = 24) or negative T waves (n = 25) on the rest 12-lead electrocardiogram and exhibited during exercise greater than or equal to 1.5 mm ST segment elevation (n = 17) or isolated T wave pseudonormalization (n = 8) in the infarct-related leads. ST-T wave changes were reproduced in all patients during thallium-201 exercise myocardial scintigraphy. A fixed perfusion defect was observed in 24 of the 25 patients. A reversible defect was seen in 16 (94%) of 17 patients who exhibited transient ST elevation during exercise but in only 4 (50%) of the 8 patients who had only T wave pseudonormalization. In conclusion, in patients with recent myocardial infarction, analysis of simple ST segment variables obtained during exercise testing may allow a first-line discrimination of those who may potentially benefit from a revascularization procedure.

Plasma levels of active Von Willebrand factor are increased in patients with first ST-segment elevation myocardial infarction: a multicenter and multiethnic study.

AIMS: Von Willebrand factor (VWF), a key player in hemostasis and thrombosis, is released from endothelial cells during inflammation. Upon release, VWF is processed by ADAMTS13 into an inactive conformation. The aim of our study was to investigate whether plasma levels of active VWF, total VWF, ADAMTS13, osteoprotegerin (OPG) and the ratios between VWF and ADAMTS13 are risk factors for first ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: We assessed 1026 patients with confirmed first STEMI and 652 control subjects from China, Italy and Scotland, within six hours after their cardiovascular event. Median plasma levels of total VWF, active VWF, OPG and ratios VWF/ADAMTS13 were increased, while plasma levels of ADAMTS13 were decreased in patients compared to controls. The odds ratio (OR) of STEMI in patients with high plasma levels of active VWF was 2.3 (interquartile range (IQR): 1.8-2.9), total VWF was 1.8 (1.4-2.3), ADAMTS13 was 0.6 (05-0.8), OPG was 1.6 (1.2-2.0) and high VWF/ADAMTS13 ratios was 1.5 (1.2-2.0). The OR for total VWF, active VWF and ratios VWF/ADAMTS13 remained significant after adjustment for established risk factors, medical treatment, C-reactive protein, total VWF, ADAMTS13 and OPG. When we adjusted for levels of active VWF, the significance of the OR for VWF and ratios VWF/ADAMTS13 disappeared while the OR for active VWF remained significant. CONCLUSIONS: We found evidence that plasma levels of active VWF are an independent risk factor for first STEMI in patients from three different ethnic groups. Our findings confirm the presence of VWF abnormalities in patients with STEMI and may be used to develop new therapeutic approaches.

Relation between myocardial infarction site and pain location in Q-wave acute myocardial infarction.

Location, severity, duration, and time course of pain were assessed in 104 consecutive patients with either first or second, anterior or inferior Q-wave acute myocardial infarction (AMI). Pain severity was assessed using a visual analog scale. Pain location and radiation were similar in 48 patients with anterior and 56 patients with inferior wall AMI. Pain duration (6.1 +/- 6.4 vs 6.5 +/- 5.4 hours, p = NS) and severity (68 +/- 21 vs 61 +/- 21 mm, p = NS) were also similar. The pain was continuous in 34 patients with anterior (71%) and in 42 with inferior (75%) wall AMI. Among the 41 patients who did not receive thrombolytic therapy, 18 patients with continuous pain had a higher creatine kinase peak level than the remaining 23 patients with intermittent pain or preinfarction angina, or both (2,065 +/- 1,017 vs 1,162 +/- 994 IU, p < 0.01). The incidence of gastrointestinal symptoms was slightly higher in patients with inferior than anterior wall AMI (70% vs 48%, p < 0.05). Among 32 patients admitted with a second AMI, pain location was similar in 14 who had both infarcts in the same myocardial region, but was different in 12 of 18 (67%) who had a first and second infarct in different regions (p < 0.001). Thus, patients with anterior or inferior wall AMI experienced pain in similar body regions. However, in patients who presented with > 1 AMI, different locations of the infarction pain were highly predictive of ischemia occurring in different myocardial regions. Finally, patients with preinfarction angina or intermittent pain tended to have smaller infarcts.

Comparison of coronary angiographic narrowing in stable angina pectoris, unstable angina pectoris, and in acute myocardial infarction.

Coronary angiographic findings were compared in patients who presented with acute myocardial infarction (AMI, n = 75), unstable angina pectoris (UAP, n = 36), or stable angina pectoris (SAP, n = 36) for > or = 2 years without evidence of any previous acute event and with an angiogram within 2 years of the initial symptoms. Angiograms were evaluated blindly for severity, extent (depending on the percentage of each coronary segment showing atherosclerosis), and pattern (discrete, < 3 loci of narrowings involving < 50% of any segment; diffuse, anything exceeding this). Patients in the SAP group had more narrowed arteries (2.4 +/- 0.7 vs 1.3 +/- 0.6 [p < 0.02] and 1.4 +/- 0.6 [p < 0.02]), more stenoses (6.0 +/- 3.3 vs 2.1 +/- 1.5 [p < 0.01] and 2.6 +/- 1.7 [p < 0.05]) and occlusions (1.3 +/- 1.1 vs 0.7 +/- 0.6 [p = 0.05] and 0.3 +/- 0.5 [p < 0.02]), and a greater extent index (0.9 +/- 0.5 vs 0.5 +/- 0.3 [p < 0.02] and 0.5 +/- 0.3 [p < 0.02]) than those in the AMI and UAP groups. Furthermore, a discrete pattern was less prevalent in patients with UAP than in those with SAP or AMI (3% vs 40% [p < 0.02] and 25% [p < 0.05], respectively). In conclusion, patients who present with acute coronary syndromes have less extensive atherosclerosis than those who present with chronic stable angina. Therefore, in the former group, coronary atherosclerosis appears to be more susceptible to ischemic stimuli responsible for acute coronary syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Ischemic-like ST-segment changes during Holter monitoring in patients with angina pectoris and normal coronary arteries but negative exercise testing.

To evaluate whether Holter electrocardiographic monitoring may improve the detection of ST-segment depression in patients with anginal chest pain and normal coronary arteries, we performed symptom-limited exercise testing and 24-hour Holter monitoring in a group of 38 such patients (27 women, age 54 +/- 8 years). Patients were divided into 2 groups:group X1 included 28 patients with and group X2 10 patients without significant ST-segment depression during exercise testing. There were no significant differences between the 2 groups in age, gender, characteristics of chest pain, exercise duration, heart rate (HR), and blood pressure at peak exercise, but anginal pain during exercise testing was reported by 10 patients of group X1 (36%) and 9 of group X2 (90%) (p <0.01). Episodes of ST-segment depression on Holter monitoring were found in 17 patients of group X1 (61%) and in 5 patients of group X2 (50%) (p = NS). There were no differences between the 2 groups in daily number of ST episodes (3.6 +/- 4 vs 2.8 +/- 5 episodes per patient), symptomatic episodes (8% vs 18%), and duration of the episodes. On average, HR increased significantly, in a similar way, from 15 minutes before ST-segment depression to 1-mm ST in both groups, and its value at the onset of ischemia was similar in the 2 groups (102 +/- 22 vs 109 +/- 18 beats/min, p = NS). Finally, HR at 1-mm ST during Holter monitoring was significantly lower than that observed at 1-mm ST during exercise testing (127 +/- 16 beats/min, p < or = 0.01) in group X1, and it was also lower than that observed at peak exercise (136 +/- 22 beats/min, p < or = 0.01) in group X2. In conclusion, Holter monitoring can significantly increase the detection of ST-segment depression in patients with anginal pain and normal coronary arteries, indicating a cardiac, although not necessarily ischemic, origin of the pain. Indeed, 50% of our patients with negative symptom-limited exercise testing showed spontaneous ST changes, compatible with transient myocardial ischemia, during daily activities. Differences in the response of coronary microvascular tone to exercise testing and to stimuli operating during daily life are likely to play a significant role in determining these findings.

Limitations of dipyridamole-echocardiography in effort angina pectoris.

The sensitivity of dipyridamole--2-dimensional (2-D) echocardiography was assessed for detection and localization of ischemia in 21 patients with severe chronic stable angina pectoris, a clearly positive exercise stress test response and multivessel coronary atherosclerosis. Regional wall motion during dipyridamole infusion (0.6 mg/kg intravenously over 4 minutes) was compared with control and recovery by 2 blinded observers in consensus. Transient regional wall motion abnormalities were observed in 11 patients. Angina and ST-segment changes occurred in 9 of these 11 patients with positive responses, but in none of those who showed no transient abnormality of regional wall motion. Localization of regional wall motion abnormalities correlated well with angiographic severity of coronary lesions. Endocardial area contraction, evaluated by a computerized system, was reduced significantly after dipyridamole administration in patients with a positive response (from 51 +/- 10% to 35 +/- 11%, p less than 0.001), whereas it did not change significantly in the others (from 43 +/- 6% to 42 +/- 8%). In the 11 patients with a positive response, coronary reserve assessed by exercise testing (modified Bruce protocol) was more impaired than in those with a negative response (time to 1 mm of ST depression 177 +/- 148 seconds and 472 +/- 179 seconds, respectively, p less than 0.01). In patients with severe angina and multivessel coronary artery disease, dipyridamole--2-D echocardiography appears to identify the vessel in which flow reserve is most limited. Although this information may be valuable, indications for the test are restricted to patients with severely limited exercise capacity.

Low incidence of serotonin-induced occlusive coronary artery spasm in patients with recent myocardial infarction.

Intracoronary infusion of serotonin has been reported to induce varying degrees of coronary vasoconstriction in different coronary syndromes, but it has never been studied in patients after myocardial infarction. In patients with recent myocardial infarction, we found a low incidence (11%) of serotonin-induced occlusive spasm only in the infarct-related artery (IRA), and a significantly higher vasoconstriction in the distal segment of the IRA than in the same segment of the non-IRA.

Role of inflammation in the pathogenesis of unstable coronary artery disease.

In this article, the clinical, angiographic, and postmortem features of unstable angina are reviewed and its pathogenesis is discussed. Coronary plaque inflammation may play a key role in the pathogenesis of unstable angina and the evidence for this assertion is examined. Finally, the therapeutic implications of the involvement of inflammation in acute coronary syndromes are outlined.

Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris.

Management of unstable angina is largely determined by symptoms, yet some symptomatic patients stabilize, whereas others develop myocardial infarction after waning of symptoms. Therefore, markers of short-term risk, available on admission, are needed. The value of 4 prognostic indicators available on admission (pain in the last 24 hours, electrocardiogram [ECG], troponin T, and C-reactive protein [CRP]), and of Holter monitoring available during the subsequent 24 hours was analyzed in 102 patients with Braunwald class IIIB unstable angina hospitalized in 4 centers. The patients were divided into 3 groups: group 1, 27 with pain during the last 24 hours and ischemic electrocardiographic changes; group 2, 45 with pain or electrocardiographic changes; group 3, 30 with neither pain nor electrocardiographic changes. Troponin T, CRP, ECG on admission, and Holter monitoring were analyzed blindly in the core laboratory. Fifteen patients developed myocardial infarction: 22% in group 1, 13% in group 2, and 10% in group 3. Twenty-eight patients underwent revascularization: 37% in group 1, 35% in group 2, and 7% in group 2 (p <0.01 between groups 1 or 2 vs group 3). Myocardial infarction was more frequent in patients with elevated troponin T (50% vs 9%, p=0.001) and elevated CRP (24% vs 4%, p= 0.01). Positive troponin T or CRP identified all myocardial infarctions in group 3. Only 1 of 46 patients with negative troponin T and CRP developed myocardial infarction. Among the indicators available on admission, multivariate analysis showed that troponin T (p=0.02) and CRP (p=0.04) were independently associated with myocardial infarction. Troponin T had the highest specificity (92%), and CRP the highest sensitivity (87%). Positive results on Holter monitoring were also associated with myocardial infarction (p=0.003), but when added to troponin T and CRP, increased specificity and positive predictive value by only 3%. Thus, in patients with class IIIB unstable angina, among data potentially available on admission, serum levels of troponin T and CRP have a significantly greater prognostic accuracy than symptoms and ECGs. Holter monitoring, available 24 hours later, adds no significant information.

Coronary risk factors: new perspectives.

The predisposing and precipitating causes of acute myocardial infarction (MI) are multiple; furthermore, different individuals may have different susceptibility, to a large extent genetically determined, to each of them. In spite of the complex aetiology of MI and of our limited knowledge of the causes responsible for the formation of persistent occlusive thrombosis in epicardial coronary arteries, the achievements obtained by controlling traditional risk factors are remarkable. Traditional risk factors, however, have a limited sensitivity among subjects with low/moderate levels of risk. Furthermore, in particular among subjects at medium risk, current preventive strategies are limited by the low incidence of preventable events which makes it necessary to also treat the vast majority of subjects who would not develop cardiac events even without any treatment. An improvement in preventive strategies for IHD can be achieved with the identification of: (1) new risk factors; (2) genotypes enhancing the susceptibility to specific risk factors; (3) phenotypes and genotypes making patients susceptible to specific preventive strategies; (4) genotypes protecting from risk factors. Although a word of caution is necessary as a number of recent studies on genetic markers, on new risk factors and on the interaction between genetic markers and environment have failed to withstand the rigour of population-based studies, the early findings available to date suggest that cost-effective preventive strategies based on individual susceptibility to specific predisposing and precipitating causes of MI may become a reality in the foreseeable future.

Differences in vasodilatory response to dipyridamole between patients with angina and normal coronary arteries and patients with successful coronary angioplasty.

BACKGROUND: Previous studies reported a reduced coronary blood flow reserve, assessed by the intravenous administration of dipyridamole, in patients with angina and normal coronary arteries, and early after successful coronary angioplasty, which suggests the presence of small coronary vessel dysfunction. This study aimed to establish whether the mechanisms of small coronary vessel disease in these two groups of patients are similar. METHODS: The effects of the intracoronary infusion of adenosine and dipyridamole (maximum dose 2.7 and 7.5 mg/min, respectively) on coronary blood flow velocity were assessed in 11 patients with angina and normal coronary arteries (group A) and in 12 patients immediately after successful coronary angioplasty (group B) using a 0.018" Doppler wire. RESULTS: Baseline coronary blood flow velocity was significantly higher in group B than group A (34 +/- 14 versus 19 +/- 8 cm/s; P = 0.001). In group A, coronary blood flow velocity was higher during adenosine than dipyridamole infusion (74 +/- 17 versus 58 +/- 21 cm/s; P < 0.001), whereas in group B velocities were similar (85 +/- 30 versus 78 +/- 32 cm/s; NS). CONCLUSIONS: In patients with angina and normal coronary arteries, a maximal dose of adenosine causes a greater coronary dilation than that of dipyridamole. Given that dipyridamole operates mainly through an inhibition of adenosine re-uptake, it can only dilate the arteriolar segments exposed to endogenous adenosine. Therefore, the lower response to dipyridamole than to exogenous adenosine observed in patients with angina and normal coronary arteries suggests an impairment of the pre-arterioles that are not influenced by endogenous adenosine, resulting in a limited flow-mediated dilation in response to arteriolar dilation. Such an impairment is not apparent immediately after successful coronary angioplasty, where the most obvious abnormality is an increase of baseline coronary blood flow velocity.

Transient microvascular vasoconstriction: a possible cause of unstable angina.

We report the case of a 65-year-old woman who developed unstable angina 2 months after successful coronary angioplasty of the left anterior descending coronary artery. Coronary angiography failed to show angiographic restenosis, but intracoronary ergonovine caused ST segment elevation and her habitual chest pain in the absence of epicardial coronary spasm and important pressure changes in the distal left anterior descending coronary artery assessed by a pressure wire, thus suggesting that distal vessel constriction was responsible for unstable angina.

Relationship between dental school performance and preprofessional major courses of study.

This study examined the records of dental students in the class of 1969 at the university of Pittsburgh School of Dental Medicine, in an attempt to determine statistically what preprofessional major was the best predictor of academic success in dental school. In the sample studied, no differences were found among the four groups-when they compared on the variable, dental school grade point average. These data suggest that the selection of the preprofessional major course of study may bear little relationship to academic performance in dental school.

[Reporting echocardiography exams with the G8-Cardio ANMCO software]. / Refertazione dell'esame ecocardiografico con il software G8-Cardio ANMCO.

BACKGROUND: The availability of a common computerized program for echocardiographic study archiving and reporting at national and/or international level could make it possible to standardize the echo reports of different echocardiographic laboratories, and to use the wealth of data thus obtainable with echocardiography, and to exploit its capillary territorial distribution, with the aim of collecting echocardiographic data in a standard format for epidemiological, scientific and administrative purposes. METHODS: To develop such a software, an ad hoc joint National Association of Hospital Cardiologists and Italian Society of Echocardiography task force worked in conjunction with the Italian Branch of Agilent Technologies to standardize the phraseology of accepted echocardiographic terms and of the quantitative parameters derived from transthoracic and transesophageal echocardiographic examination at rest as well as during exercise and pharmacological stress, and to develop an ad hoc software. This echocardiographic study archiving and reporting program is part of the whole G8-Cardio ANMCO software developed to computerize the whole cardiological chart. The software has been developed by Agilent Technologies to provide a fast, easy-access and easy to use report generator for the non-computer specialist using DBMS Oracle 7.3 database and Power Builder 5.0 to develop a user-friendly interface. RESULTS: The number of qualitative and quantitative variables contained in the program is 733 for echocardiography at rest, while it depends on the stressor and on the length of the examination for the stress echo (dipyridamole 214-384, dobutamine 236-406, exercise 198-392). The program was tested and refined in our laboratory between November 1999 and May 2000. During this time period, 291 resting and 56 stress echocardiographic studies were reported and recorded in a database. On average, each resting echocardiographic study lasting 10 +/- 4 (range 5-17) min was recorded using 50 +/- 11 (range 33-67) variables and 41,566 bytes of hard-disk memory space. Stress echocardiographic studies, each lasting 7 +/- 5 (range 5-21) min, were recorded using 143 +/- 74 (range 38-194) variables and 38,531 bytes of hard-disk memory space. CONCLUSIONS: To our knowledge this software represents the first experience of a common computerized program for echo archiving and reporting carried out at national level.