Prevalence of celiac disease and symptoms in relatives of patients with celiac disease.

BACKGROUND AND OBJECTIVES: We determined the prevalence and clinical features of celiac disease (CD) in family-members (FMs) of a population-based cohort of index cases. MATERIALS AND METHODS: We recruited 108 CD index cases: mean age at diagnosis, 23.0 years (range, 1.5-45.2 years); 81 (75%) female. Three-hundred twelve (mean age, 41.6 years; 219 [70%] female) of FMs were analyzed. 153 (49%) were parents, 24 (7.7%) were children, 69 (22.2%) were siblings, 66 (21.1%) were second degree FMs. RESULTS: CD was diagnosed in 63 subjects (20.1%, 21 males and 42 females, mean age 34.24 years, range 2-81 years). Classic, subclinical, and silent forms of CD were recognized in 18 [28.6% (6 siblings, 6 parents, 3 child, 3 second-degree FMs)], in 27 [45.8% (9 siblings, 3 parent, 15 second-degree FMs)], and in 18 [28.6% (6 siblings, 6 parents, 6 second-degree FMs)] cases, respectively. Most of patients suffering from "classical" (18/63 patients, 28.7%) and "subclinical" (27/63 patients, 42.9%) form of CD were older than patients suffering from "silent " CD (18/63 patients, 28.7%) (p=0.01). Most of patients suffering from subclinical disease showed autoimmune diseases (Hashimoto's thyroiditis, and psoriasis), and other atypical symptoms, as gastroesophageal reflux disease (GERD), were also recorded. CONCLUSIONS: We found an high-prevalence of CD between CD FMs, and most of them were olygo- or asymptomatic.

A comparison of coronary artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery: five year clinical follow up.

BACKGROUND: Stent implantation for isolated stenosis of the proximal left anterior descending coronary artery (LAD) with preserved left ventricular function has been found to have a better clinical and angiographic outcome at one year than balloon angioplasty (PTCA). OBJECTIVE: To establish whether those results are maintained at five year follow up. METHODS: Patients were followed at least every six months. For those who died during follow up, data were obtained from medical records. MAIN OUTCOME MEASURES: Freedom from death, non-fatal myocardial infarction, cerebrovascular accident, and repeated target lesion revascularisation. Secondary end points were revascularisation in a remote region and freedom from angina. RESULTS: Follow up was complete in all patients. At five years, the primary end point was reached more often by patients randomised to stent implantation than to PTCA (80% v 53%; odds ratio (OR) 0.29 (95% confidence interval (CI) 0.13 to 0.69); p = 0.0034). In the PTCA group, 35% of patients underwent target lesion revascularisation v 15% in the stent group (OR 0.33, 95% CI 0.13 to 0.80; p = 0.014). There was a trend towards increased mortality in the PTCA group than in the stent group (17% v 7%; OR 0.36, 95% CI 0.10 to 1.21; p = 0.098). No significant differences were found between PTCA and stent groups for non-fatal myocardial infarction (8% v 5%; OR 0.58, 95% CI 0.13 to 2.54; p = 0.46) or cerebrovascular accident (2% v 0%). CONCLUSIONS: In patients with isolated stenosis of the proximal LAD, a five year clinical follow up confirmed a better outcome in those treated with stenting than with PTCA.

Acute thrombosis of the sinus node artery: arrhythmological implications.

A 53 year old woman was referred for percutaneous coronary intervention because of a recent inferior myocardial infarction. During right coronary artery stent implantation, intermittent occlusion of the coronary side branch for the sinus node occurred, associated with intermittent sinus arrest and junctional escape rhythm. This led to speculation about the potential mechanisms for sinus node dysfunction. Degenerative fibrosis of nodal tissue is actually considered the most common cause of bradyarrhythmias. Yet, in everyday practice, no particular attention is usually paid to other potential pathogenic mechanisms such as coronary artery disease. This may be particularly true for elderly patients or patients with multiple risk factors. Thus, sinus node dysfunction may be an unrecognised marker of coronary artery disease.

Unstable angina and elevated c-reactive protein levels predict enhanced vasoreactivity of the culprit lesion.

BACKGROUND: Because plaque inflammation may modulate coronary vasomotion, the association between systemic levels of C-reactive protein (CRP) and coronary vasoreactivity was assessed in patients with stable or unstable angina. METHODS AND RESULTS: In 31 patients with stable angina and 23 patients with unstable angina undergoing coronary angiography, minimal luminal diameter (MLD) of the culprit lesion was measured by quantitative coronary angiography at baseline, during the cold pressor test (CPT), and after intracoronary administration of nitroglycerin (NTG) and expressed as percent change from baseline. MLD of patients with unstable angina exhibited a greater reduction during CPT and a greater increase after NTG than did patients with stable angina (-17+/-14% versus -5+/-12%, P=0.0013, and 34+/-25% versus 8+/-20%, P<0.001, respectively). According to preprocedural serum levels of CRP, 36 patients had normal (

The use over time of statins in coronary patients in an Italian tertiary referral center.

BACKGROUND: In the last decade, large-scale clinical trials have consistently shown that therapy with statins is of great benefit to patients with and at risk of developing coronary artery disease. We assessed, in a sample of patients with coronary artery disease in whom coronary angiography was indicated and hospitalized in the last 10 years, the use of statins at admission. METHODS: One hundred patients with stable coronary artery disease were randomly selected per year from 1991 to 2000. The final study population consisted of 1000 patients. The prescription of statins for > or = 6 months before hospital admission was determined from a hospital-wide clinical database. RESULTS: From 1995, the prevalence of patients treated with statins at hospital admission progressively increased. In 1991, only 2% of patients were treated with statins before hospital admission while in the year 2000, 38% of patients were receiving this treatment. The mean prevalence of patients treated with statins before and after 1995 was 3 vs 22% (p < 0.0001) respectively. The distribution of the demographic and clinical parameters and the prevalence of conventional cardiovascular risk factors were similar in patients treated or not treated with statins. CONCLUSIONS: After 1994, in coincidence with the publication of the results of clinical trials showing the benefit of statins in patients with coronary artery disease, the use of these drugs increased significantly. This finding suggests that the widespread diffusion of the results of the major clinical trials and of guidelines drawn up by medical associations have had a significant impact on statin prescription in patients with coronary artery disease. Nevertheless our data also indicate that, despite overwhelming evidence on the benefits of statin therapy, in current clinical practice cardiologists are not optimally utilizing lipid management and that statins are frequently prescribed without an appropriate analysis of risk factors.

Mechanisms of myocardial ischemia in a patient with left main coronary artery atresia.

This report describes the different clinical and instrumental manifestations of coronary ischemia in a patient with left main coronary artery atresia. Exercise test and thallium-201 perfusion scintigraphy during isometric exercise test were negative for angina and electrocardiographic changes. Conversely, dipyridamole infusion caused severe angina, marked ST-segment changes and diffuse thallium-201 uptake abnormalities. This peculiar anatomical condition offers the opportunity of high-lighting the role played by the microcirculation in determining myocardial ischemia.

A prospective randomized trial comparing stenting to internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis: the SIMA trial. Stenting vs Internal Mammary Artery.

OBJECTIVE: To compare coronary artery bypass grafting (CABG) with percutaneous transluminal coronary angioplasty (PTCA) in patients with proximal, isolated de novo left anterior descending coronary artery disease and left ventricular ejection fraction of 45%. PATIENTS AND METHODS: In the multicenter Stenting vs Internal Mammary Artery (SIMA) study, patients were randomly assigned to PTCA and stent implantation or to CABG (using the internal mammary artery). The primary clinical composite end point was event-free survival, including death, myocardial infarction, and the need for additional revascularization. Secondary end points were functional class, antianginal treatment, and quality of life. Analyses were by intention to treat. RESULTS: Of 123 patients who accepted randomization, 59 underwent CABG, and 62 were treated with stent implantation (2 patients were excluded because of protocol violation). At a mean +/- SD follow-up of 2.4+/-0.9 years, a primary end point had occurred in 19 patients (31%) in the stent group and in 4 (7%) in the CABG group (P<.001). This significant difference in clinical outcome is due to a higher incidence of additional revascularization in the stent group, the incidence of death and myocardial infarction being similar (7% vs 7%, respectively; P=.90). The functional class, need for antianginal drug, and quality-of-life assessment showed no significant differences. CONCLUSIONS: Both stent implantation and CABG are safe and highly effective treatments to relieve symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Both are associated with a low and comparable incidence of death and myocardial infarction. However, similar to PTCA alone, a percutaneous approach using elective stent placement remains hampered by a higher need for repeated intervention because of restenosis.

Endothelial activation in patients with cardiac syndrome X.

BACKGROUND: The presence of endothelial dysfunction with increased endothelin-1 plasma concentrations in patients with cardiac syndrome X is still under debate. The aim of the present study was to evaluate the presence of endothelial dysfunction in patients with cardiac syndrome X. METHODS AND RESULTS: ++Endothelin-1 levels were evaluated with a sensitive radioimmunoassay with previous purification through reverse phase HPLC in 24 patients (3 men and 21 women, mean age 54+/-7 years) with typical angina, instrumental evidence of ischemia, and normal coronary angiograms both under baseline conditions and after oral glucose load (75 g D-glucose). We also measured plasma nitrite-plus-nitrate levels, a sharp index of endothelial nitric oxide production, and circulating concentrations of the soluble fraction of the endothelial adhesion molecule vascular cell adhesion molecule-1, a well-recognized marker of early endothelial dysfunction. Fourteen healthy subjects (1 man and 13 women, mean age 47+/-15 years) served as controls. There were no significant differences in baseline plasma endothelin-1 concentrations between patients and control subjects (0.55+/-0.34 versus 0.48+/-0.22 pg/mL, P=0.503). Plasma nitrite-plus-nitrate and soluble vascular cell adhesion molecule-1 concentrations were also similar between the 2 groups. After glucose ingestion, circulating endothelin-1 concentrations were significantly higher in patients with cardiac syndrome X than in control subjects (P<0.03 at 60, 90, and 120 minutes). CONCLUSIONS: Our findings show that no basal endothelial damage is present in patients with cardiac syndrome X. Nevertheless, increased responsiveness of endothelin-1 to glucose loading suggests that patients with cardiac syndrome X present an increased susceptibility to releasing endothelin-1 under stressful circumstances.

Predictive value of C-reactive protein in patients with unstable angina pectoris undergoing coronary artery stent implantation.

This study was aimed at establishing the relation between baseline C-reactive protein levels and 12-month outcome in patients with unstable angina successfully treated with coronary artery stent implantation. Our results suggest that in patients with unstable angina and 1-vessel coronary disease successfully treated with coronary artery stent implantation, normal baseline serum levels of C-reactive protein identify a subgroup of patients at low risk of cardiac events during follow-up.

Ischemic preconditioning during coronary angioplasty is preserved in elderly patients.

BACKGROUND: To establish whether the adaptation to ischemia observed in humans during percutaneous transluminal coronary angioplasty (PTCA) after repeated balloon inflations, i.e. a clinical correlate of ischemic preconditioning, is preserved in elderly patients. METHODS: We studied 53 consecutive patients undergoing successful angioplasty for an isolated stenosis of a major epicardial coronary artery. On the basis of age, patients were separated into terciles: patients in the lower and middle terciles were grouped together (Group 1, adult patients, n = 24, mean age 50 +/- 6 years) and compared with those in the upper tercile (Group 2, elderly patients, n = 29, mean age 68 +/- 3 years). Intracoronary electrocardiogram was obtained at the end of the first two balloon inflations. Collateral recruitment during repeated balloon inflations was assessed by using an intracoronary Doppler guide wire (23 patients) or by using an intracoronary pressure guide wire (30 patients). RESULTS: In Group 1, ST-segment changes during the second inflation were significantly less than those at the end of the first inflation (6 +/- 3 vs 13 +/- 5 mm, p < 0.001). Similarly, in Group 2, ST-segment changes during the second inflation were significantly less than those at the end of the first inflation (6 +/- 4 vs 13 +/- 6 mm, p < 0.001). In both groups, collateral recruitment did not change from the first inflation to the second inflation (p = 0.1). CONCLUSIONS: Our study confirms that adaptation to ischemia during repeated balloon inflations in the setting of PTCA is independent of collateral recruitment and, therefore, is mainly due to ischemic preconditioning. More importantly, our study indicates that ischemic preconditioning is preserved in elderly patients.

Regional distribution and timing of wall motion abnormalities during echo-dipyridamole stress test in patients with stable angina: the elusive link between coronary stenoses and myocardial ischemia.

BACKGROUND: Classic experimental studies have shown that in the presence of a flow-limiting coronary artery stenosis, myocardial ischemia during metabolic or pharmacological arteriolar vasodilation causes wall motion abnormalities, which precede electrocardiographic (ECG) changes in the myocardial regions supplied by the stenotic branch. The aim of this study was to establish whether in patients with chronic stable angina the regional distribution of wall motion changes and sequence of ischemic events are similar to that observed in experimental models, as currently believed. METHODS: The study population consisted of 20 men and 4 women (mean age 59 +/- 10 years) who were recruited on the basis of the following criteria: 1) a history of chronic stable angina without clinical and instrumental evidence of previous myocardial infarction; 2) reproducible positive exercise tests for ECG myocardial ischemia and anginal pain; 3) angiographically normal left ventricular function; 4) isolated stenosis of the left anterior descending coronary artery (LAD). Patients underwent continuous 12-lead ECG and echocardiographic monitoring during dipyridamole infusion. RESULTS: During dipyridamole infusion 3 patients (13%) did not develop echocardiographic changes, ECG changes or angina, 14 (58%) exhibited ECG changes, 18 (75%) lamented angina and 16 (67%) developed echocardiographic changes. In 5 of these 16 patients (31.5%) echocardiographic changes occurred in LAD-dependent territories only, in 5 they occurred in non-LAD-dependent territories only (31.5%) and in 6 (37%) they occurred in both LAD- and non-LAD-dependent territories. A total of 14 patients exhibited both echocardiographic and ECG changes and/or angina. In 6 of these 14 patients (43%) echocardiographic changes were the first ischemic events; in the remaining 8 patients (57%) ECG changes and/or angina were the first ischemic events. CONCLUSION: In the majority of patients during dipyridamole infusion regional wall motion changes occur in territories supplied by non-stenotic coronary artery branches; they are probably caused, therefore, by distal vessel dysfunction. Furthermore, the sequence of ischemic events is different in individual patients. These findings indicate that in stable angina the mechanisms of ischemia are multiple and that the link between coronary stenoses and myocardial ischemia is very elusive.

Algogenic effects of the proximal and distal intracoronary infusion of adenosine. Pathophysiologic implications on the mechanisms of ischemic cardiac pain.

BACKGROUND: It has been hypothesized that ischemic cardiac pain might be due to a spatially restricted intense stimulation of non-specific cardiac receptors. If this hypothesis is correct a strong stimulation with an adequate stimulus of a limited myocardial region should cause more pain than a weaker stimulation of a larger myocardial region. METHODS: To test this hypothesis, we carried out a systematic study in 8 male patients (mean age 52 +/- 9 years) with uncomplicated stable angina pectoris and significant isolated proximal left anterior descending coronary artery stenosis in whom the same amount of adenosine, a known mediator of cardiac and muscular ischemic pain, was infused at the proximal and distal site of the left anterior descending coronary artery. Increasing doubling doses (from 108 to 3456 micrograms/min) or adenosine were infused for periods of 2 min each into the left anterior descending coronary artery through a 2.8 F catheter. Adenosine was infused in each patient both proximally to the first diagonal branch and distally to the last diagonal branch of the left anterior descending coronary artery. The initial infusion site, proximal or distal, was randomized. At the beginning of the study patients were asked to promptly report the onset of pain. Time to onset of adenosine-induced pain and maximal pain severity (assessed by a visual analog scale) were recorded. Twelve electrocardiographic leads were recorded throughout the study. RESULTS: Seven patients experienced pain during adenosine infusion both at the proximal and distal level. One patient experienced pain only during adenosine infusion at the proximal site. In all patients pain occurred earlier (176 +/- 125 vs 343 +/- 207 s, p = 0.005) and its severity was greater (51 mm, range 20-95, vs 27 mm, range 0-69, p = 0.002) during infusion at the proximal site. No patient exhibited electrocardiographic changes during the study. CONCLUSIONS: Adenosine infusion at a proximal coronary site causes pain which occurs earlier and is more severe than that experienced during its infusion at a distal site. These findings suggest that the intensity of ischemic cardiac pain is determined by the number of stimulated receptors rather than by the intensity of their stimulation.

Coronary flow reserve early and late after minimally invasive coronary artery bypass grafting in patients with totally occluded left anterior descending coronary artery.

BACKGROUND: The impairment of flow reserve of the left anterior descending coronary artery in the early postoperative period in patients receiving a left internal thoracic artery graft has been related to the effects of cardiopulmonary bypass. Indeed, the late improvement in flow has been attributed to a late increase in left internal thoracic artery diameter. METHODS: We evaluated 12 patients who underwent minimally invasive direct coronary artery bypass surgery with the internal thoracic artery used to graft an occluded left anterior descending artery without extracorporeal circulation. Early and 6 months after the operation, patients underwent a second angiogram of the left internal thoracic artery graft and assessment of coronary flow reserve by use of an intracoronary 0.014-inch Doppler guide wire. RESULTS: At the late study, coronary flow reserve had increased compared with the early postoperative data from 1.8 +/- 0.4 (standard deviation) to 2.5 +/- 0.6 (P =.002) because of a significant decrease in baseline averaged peak velocity (32.4 +/- 6.2 vs 21.3 +/- 6.4 cm/s, P =.002), whereas the hyperemic values were similar (51 +/- 6 vs 53.7 +/- 21.9 cm/s, P =.6). The diameters of the thoracic artery (2.1 +/- 0.3 vs 2.2 +/- 0.3 mm, P =. 7) and the left anterior descending coronary artery (1.8 +/- 0.1 vs 1.8 +/- 0.2 mm, P =.5), as well as myocardial oxygen consumption (106 +/- 14 vs 101 +/- 16 mm Hg. beats/min. 10(-2), P =.5), were unchanged. CONCLUSIONS: Our findings suggest that the late improvement in coronary flow reserve is independent of the diameter of the graft and probably reflects an early distal coronary vessel dysfunction, which normalizes with time.

Decreased activity of the red blood cell ATPase-dependent Na+ pump in patients with cardiac syndrome X.

Marked Na(+)/Li(+) countertransport hyperactivity and post-load hyperinsulinaemia have been described in 93% of patients with cardiac syndrome X. We hypothesized that more complex abnormalities in Na(+) traffic across the cell membrane are present in these patients. The aim of the present study was to evaluate the activities of the two main transporters responsible for transmembrane Na(+) transport, i.e. the ATPase-dependent Na(+) pump and the Na(+)-K(+)-2Cl(-) co-transporter, in a selected group of patients with cardiac syndrome X. We evaluated 19 patients with cardiac syndrome X and 14 control subjects. The ATPase-dependent Na(+) pump and Na(+)-K(+)-2Cl(-) co-transport activities were assessed from Na(+)-loaded red blood cells by using nystatine, in the presence of furosemide and ouabain, as appropriate. Erythrocyte Na(+)/Li(+) countertransport activity, serum lipid and post-load (75 g of oral glucose) insulin levels were also evaluated. The V(max) of Na(+)/Li(+) countertransport (P=0.0001) and post-load insulin levels (120 min; P=0.001) were confirmed to be higher in patients with syndrome X than in controls. The V(max) of Na(+)-K(+)-2Cl(-) co-transport was similar in patients and controls. By contrast, the V(max) of the ATPase-dependent Na(+) pump was significantly lower (P=0.002) in syndrome X patients (3.13+/-0.87 mmol.h(-1).l(-1)) than in controls (4.28+/-1.10 mmol.h(-1).l(-1)). Serum total cholesterol and triacylglycerol concentrations were also higher in patients with syndrome X than in control subjects (P<0.0001). Thus decreased activity of the ATPase-dependent Na(+) pump was present in patients with cardiac syndrome X. Such an abnormality has the biological potential to augment microvascular tone and the response to constrictor stimuli via increased intracellular free Ca(2+). Of note, syndrome X patients also manifested Na(+)/Li(+) countertransport hyperactivity which, in turn, is known to induce peripheral insulin resistance and consequent abnormalities in insulin secretion and lipid turnover. Thus cardiac syndrome X appears as a multifaceted syndrome presenting with either metabolic or cardiovascular symptoms, or both, based on the expression of complex abnormalities in Na(+) traffic across the cell membrane.

Effect of acetylsalicylate on cardiac and muscular pain induced by intracoronary and intra-arterial infusion of bradykinin in humans.

OBJECTIVES: This study assessed the algesic activity of bradykinin (BK) in humans and the effects of acetylsalicylate on muscular and cardiac BK-induced pain. BACKGROUND: Bradykinin is released by the ischemic myocardium and may be involved in the genesis of ischemic pain. METHODS: Increasing doses of BK (from 30 to 960 ng/min) were randomly infused, for periods of 2 min each, into the iliac artery of 10 patients. The same protocol was repeated 30 min after the IV administration of 1 g of acetylsalicylate. In eight other patients with coronary artery disease, the same increasing doses of BK, for periods of 2 min each, were infused into the left coronary artery. The same protocol was repeated 30 min after the IV administration of 1 g of acetylsalicylate. Time to pain onset and maximal pain severity were obtained. RESULTS: Before acetylsalicylate administration, all patients experienced pain during intra-iliac infusion of BK. After acetylsalicylate, eight patients did not experience any pain during BK infusion (p = 0.0014), and in the two remaining patients, time to pain onset and maximal pain severity were similar to those recorded before acetylsalicylate. Before acetylsalicylate administration, all patients experienced pain similar to their habitual angina during intracoronary BK infusion. After acetylsalicylate, six patients did not experience any pain during BK infusion (p = 0.0098), whereas in the two remaining patients time to pain onset and maximal pain severity were similar to those recorded before acetylsalicylate. CONCLUSIONS: Intra-iliac infusion of BK causes muscular pain, and its intracoronary infusion in patients with coronary artery disease causes cardiac pain, which is similar to their habitual angina. The BK-induced pain is abolished or reduced by acetylsalicylate, thus suggesting that acetylsalicylate-sensitive mediators, such as prostaglandins, are involved in its pathogenesis.

Coronary artery stent placement in patients with variant angina refractory to medical treatment.

We performed a prospective study to establish the efficacy of coronary stent placement in a highly selected group of patients with focal coronary artery spasm in whom anginal attacks could not be prevented by full medical therapy. The results of this study indicate that intracoronary stent placement may represent an alternative and feasible treatment for patients with vasospastic angina refractory to aggressive medical therapy.