Oesophagitis and bile reflux gastritis—clinical and histological assessments

BACKGROUND AND AIMS: Little is known concerning the relationship between oesophagitis and bile reflux (chemical) gastritis despite the numerous studies on gastritis related to Helicobacter pylori. Given the importance of bile in the pathogenesis of both gastric and oesophageal disorders, we aimed at assessing the chemical gastritis score in patients with or without oesophagitis. METHODS: Chemical/bile reflux gastritis score and bile reflux index were assessed in gastric biopsies taken from patients with oesophagitis and gastric surgery (group 1, n=9), gastric surgery without oesophagitis (group 2, n= 11), and oesophagitis without gastric surgery (group 3, n= 10). Endoscopic oesophageal damage was also graded on a 0-5 scale. RESULTS: Group 1 had a median (interquartile range) chemical score of 6 (4-9) compared with 8 (6-10) in group 2, and 1 (0-2) in group 3 (p=0.001; Kruskal-Wallis test for multiple group comparisons). Both the reflux gastritis score and bile reflux index were lowest in patients with intact stomachs. However, the oesophageal scores were 2 (1-2) in group 1 compared with 3 (2-5) in group 3 (p=0.01). CONCLUSION: Patients with post-surgical stomachs have similar chemical and related scores regardless of the presence or absence of oesophagitis. Despite the higher chemical gastritis scores, patients with gastric surgery, exposed mainly to bile reflux, have milder oesophagitis than those with intact stomachs, exposed to both gastric acid and bile.     

Patterns of acid reflux in complicated oesophagitis.

Oesophageal manometry and 24 hour ambulatory pH recordings from the distal oesophagus were carried out in 25 patients with complications of oesophagitis (stricture, Barrett's oesophagus or oesophageal ulcer) and compared with 25 patients with uncomplicated oesophagitis. Acid reflux was more severe in the complicated group with 26.2% of time below pH 4 compared with 11.3% in uncomplicated patients (p less than 0.01). This difference was most marked at night, when complicated patients had long periods of acid reflux with 35.6% time less than pH 4 compared with 5.2% uncomplicated (p less than 0.001). The mean duration of nocturnal acid reflux was 15.4 minutes (2.1 minutes uncomplicated, p less than 0.001). Oesophageal motility was markedly abnormal in all groups, but with no demonstrable differences in lower oesophageal sphincter pressure or peristalsis between the groups. Patients with complications of oesophagitis have different patterns of acid reflux from uncomplicated patients, with prolonged nocturnal bathing of the oesophageal mucosa, which may be the cause of stricture formation, metaplasia, or ulceration.     

Fundal gastritis as a potential cause of reflux oesophagitis

The transient lower oesophageal sphincter relaxations which allow reflux may be due to altered afferent pathways from the fundus. We aimed to determine whether fundal inflammation is the underlying cause. Two endoscopic biopsies were taken from each of the gastric antrum and fundus in 25 asymptomatic controls with a normal endoscopy (median age 54 range 13-83 years), and 33 patients with erosive oesophagitis (median age 52, 11-78 years). No patient had taken acid suppression therapy or antibiotics for at least 1 month. Sections were stained with haematoxylin and eosin and Giemsa stain and examined in a blinded fashion by one pathologist for the presence of gastritis (Sydney classification) and Helicobacter pylori. Chronic gastritis was common in both groups, but was usually mild. In Helicobacter pylori-negative subjects, there was significantly less chronic gastritis in the antrum and the fundus in oesophagitis patients than in controls (p < 0.05). When present, gastric atrophy was usually antral and mild in severity. There was no difference in the incidence of gastric atrophy in patients with oesophagitis compared with controls (24% compared with 40%; p > 0.05). Chronic gastritis is not more common in patients with oesophagitis, and is unlikely to play a part in the pathogenesis of this disease.     

The prevalence of urinary incontinence and use of incontinence aids in 85-year-old men and women

The prevalence of urinary incontinence and the use of incontinence aids was investigated in 85-year-old men and women resident in the city of G?teborg. The overall prevalence of urinary incontinence was 37.2%. Urinary incontinence was more prevalent (p less than 0.001) in women (43.2%) than men (24.0%), and in residents of a nursing home or hospital (83.9%) than in men and women living at home (29.4%). Urinary incontinence was more commonly encountered in men with neurological (p less than 0.001) and respiratory (p less than 0.05) illnesses, and in women suffering from cardiovascular (p less than 0.05), neurological (p less than 0.001) and urogenital (p less than 0.01) illnesses. Incontinence aids were used more often (p less than 0.001) by incontinent women (67.9%) then men (42.9%) living in the community, and were used by 86.4% of the incontinent men and 91.5% of the incontinent women living in an institution. Pads were the commonest form of incontinence aid used, irrespective of whether the men and women lived in the community or in an institution. Indwelling urinary catheters were used by only 2% of the 85-year-old men and women.     

Incidence of large oesophageal varices in patients with cirrhosis: application to prophylaxis of first bleeding.

Because several studies have suggested that beta blockers are effective in the prophylaxis of first variceal bleeding in cirrhosis, screening for oesophageal varices might be appropriate. We prospectively studied 84 cirrhotic patients without obvious evidence of large oesophageal varices and previous bleeding during a mean follow up of 16 months. At entry to the study 41 patients had no oesophageal varices and in 43 these were grade 1. The subsequent percentages of patients without large oesophageal varices were 74% at one year and 52% at two years. Univariate analysis showed that a longer duration of cirrhosis (p less than 0.05) and grade 1 oesophageal varices at entry (p less than 0.001) were predictive factors for the occurrence of large oesophageal varices, whereas, multivariate analysis showed that the initial size of the oesophageal varices (p less than 0.001), a high initial Child-Pugh score, and a smaller improvement in Child-Pugh score during the study were independent risk factors. Among patients with grades 0 and 1 oesophageal varices at the start of the study the proportions with large oesophageal varices at two years were 31% and 70% respectively. We have calculated that, accepting a maximum risk of first bleeding of 10% without prophylactic treatment, a patient without oesophageal varices should be screened endoscopically every other year, while a patient with grade 1 disease should benefit from one annual upper gastrointestinal endoscopy.     

Intravariceal versus paravariceal sclerotherapy: a prospective, controlled, randomised trial.

Fifty four consecutive patients with oesophageal variceal bleeding were randomised to undergo intravariceal (28 patients) or paravariceal (26 patients) sclerotherapy, every three weeks. Intravariceal technique was found significantly (p less than 0.01) more effective in controlling active variceal bleeding than the paravariceal technique (91% v 18.7% respectively). The mean (+/- SD) time taken for variceal eradication by intravariceal sclerotherapy (15.4 +/- 5.3 weeks) was significantly (p less than 0.001) less than paravariceal (26.8 +/- 6.6 weeks) technique. The number of sclerotherapy sessions needed with intravariceal technique were also significantly less. Rebleeding was seen in 38.5% patients after para and 14.3% after intravariceal injections (NS). Except for retrosternal pain, which occurred more often (p less than 0.01) with paravariceal technique, there was no difference in the incidence of other complications or mortality between the two groups. Variceal recurrence was seen in seven patients (25%) in the intra and one (3.9%) patient in the paravariceal group (p less than 0.01) after a mean follow up of 29.4 +/- 9.1 weeks. Intravariceal sclerotherapy was superior to paravariceal in the control of active variceal bleeding and for total variceal obliteration, but was associated with a higher variceal recurrence.     

Yield of endoscopy in children with hematemesis.

Upper gastrointestinal (UGI) endoscopy is an important tool in the evaluation of patients presenting with haematemesis. The objective of this study was to report the yield of this procedure in a Saudi Arabian population. We analysed the result UGI endoscopy in children and adolescents of 0-18 years of age who presented with haematemesis over a period of 10 years. From 1993 to 2003, endoscopy was performed on 60 consecutive children presenting with haematemesis. This group represented 12% of the indications during the same period. The majority (98%) were Saudi nationals, with an age range from 4 days to 18 years, and a male to female ratio of 1:1.5. The overall yield of endoscopy was 75%; however, the yield was higher (91%) in children below 12 years of age. Gastritis was the commonest cause of haematemesis (44%), followed by oesophagitis (36%). However, age-related analysis shows that oesophagitis was a more common cause of haematemesis in the younger age group (45%) than gastritis in adolescents (30%). In contrast, gastritis was more common in older children (56%) than oesophagitis (28%). Peptic ulcer disease and oesophageal varices were seen in only 3 (7%) and 2 children (4.3%), respectively. The overall yield of endoscopy in our patients is similar to that in most reports. However, oesophagitis and gastritis were the commonest causes of haematemesis, whereas oesophageal varices and peptic ulcer disease were much less common.     

Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole

BACKGROUND: Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking. AIM: To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease. METHODS: Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed. RESULTS: Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole (p=0.026). CONCLUSIONS: Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.     

Gastrointestinal causes of refractory iron deficiency anemia in patients without gastrointestinal symptoms.

BACKGROUND: The standard evaluation of a patient with iron deficiency anemia includes a complete evaluation of the gastrointestinal tract to identify a source of bleeding. However, even after a careful examination, many patients remain without a diagnosis. Because iron deficiency anemia results from iron loss or defective absorption, we sought to determine the prevalence of potential gastrointestinal sources for iron deficiency anemia in patients without gastrointestinal symptoms. METHODS: Over a 10-month period, 668 outpatients were referred to the University Hematology Department with iron deficiency anemia, defined by a hemoglobin concentration less than 14 g/dL (less than 12 g/dL in women), mean corpuscular volume less than 80 fL, and ferritin level less than 30 microg/L. After excluding patients with obvious causes of blood loss, inadequate diet, chronic diseases, or malignancies, there were 81 eligible patients, 10 of whom refused investigation. The remaining 71 patients (51 women, median age 59 years) underwent colonoscopy, as well as gastroscopy with gastric (antrum and body) and duodenal biopsies. RESULTS: A likely cause of iron deficiency anemia was detected in 60 patients (85%). Diseases associated with bleeding were found in 26 patients (37%), including colon cancer (10 patients), gastric cancer (2), peptic ulcer (7), hiatal hernia with linear erosions (5), colonic vascular ectasia (3), colonic polyps (2), and Crohn's disease (1). Causes not associated with bleeding were found in 36 patients (51%), including 19 with atrophic gastritis, 4 with celiac disease, and 13 with Helicobacter pylori gastritis. Six (8%) patients had coincident gastrointestinal findings, and 11 (15%) had no cause identified. Patients with an identified nonbleeding-associated cause were younger than those with a bleeding-associated cause (median, 56 vs 70 years; P = 0.001) and included 59% of women (n = 30) versus 30% of men (n = 6) (P = 0.04). Hemoglobin level was not related to the site and severity of disease. CONCLUSION: Gastrointestinal diseases that do not usually cause bleeding are frequently associated with iron deficiency anemia in patients without gastrointestinal symptom or other potential causes of gastrointestinal bleeding.     

Clinical profile and results of transluminal coronary angioplasty in women. Comparison with men

To determine if the results of percutaneous transluminal coronary angioplasty are similar in women and in men or any difference between both sexes exists, we have compared 43 clinical and 61 angiographic or procedural variables of 85 consecutive transluminal coronary angioplasties performed in women with 421 similar consecutive procedures in men. Only cigarette smoking was more frequent in men (84 vs 11%, p less than 0.001), being the remaining coronary risk factors more common in women (hypertension 69% vs 37%, p less than 0.001; hypercholesterolemia 46% vs 33%, p less than 0.05, and diabetes mellitus 42% vs 14%, p less than 0.01). In addition, unstable angina was a more frequent indication of coronary angioplasty in women than in men (74% vs 61%, p less than 0.05), whereas coronary angioplasty after intravenous thrombolysis was more frequent in men (12% vs 1%, p less than 0.001). Coronary angioplasty angiographic success (87% vs 91%), and minor (16% vs 10%) or major (5% vs 3%) complications were not statistically different in the two groups. Nevertheless, success of the procedure in the absence of any complication was achieved in a higher percentage (86% vs 76%, p less than 0.05) of men than in their female counterparts. After coronary angioplasty 88% of women had an angiographic follow-up available which yielded a restenosis rate of 41% (vs 32% in men, NS), despite the absence of symptoms in the 89% of these patients in their last visit. In conclusion, we have found that the feminine population subjected to coronary angioplasty have a higher incidence of coronary risks factors and more frequently unstable angina than the masculine group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Benign oesophageal stricture in Barrett's columnar epithelialised oesophagus and its responsiveness to conservative management.

The response to treatment of peptic oesophageal stricture associated with columnar lined (Barretts) oesophagus (CLO) has been compared with that in peptic stricture without CLO. Benign oesophageal stricture was present in 23 (41%) of 56 patients consecutive with CLO. In 18 the stricture lay at the squamocolumnar mucosal junction and was associated with reflux oesophagitis, in five it was situated in the columnar lined segment and in four of these it was known to have been preceded by a chronic ulcer at the site of the stricture. Controls were an age and sex matched group of patients with benign stricture related to reflux oesophagitis unassociated with columnar epithelialisation. CLO associated strictures involving squamous mucosa were situated significantly (p less than 0.01) higher in the oesophagus than non-CLO strictures. The response to endoscopic dilatation and active medical treatment was significantly better, as judged by the need for subsequent dilatation (p less than 0.01) in the CLO than in the non-CLO group. It is concluded that associated columnar epithelialisation of the oesophagus is not in itself an indication for antireflux surgery in the management of benign stricture and these usually respond well to dilatation and medical treatment.     

Relationship of hiatus hernia to reflux oesophagitis. A prospective study of coincidence, using endoscopy

A prospective study of the incidence of hiatus hernia and/or reflux oesophagitis was carried out in 670 patients referred for routine upper alimentary endoscopy. Hiatus hernia was found in 16.6% and reflux oesophagitis in 15.1% of the patients. Forty-two per cent of the patients with hernia did not have oesophagitis, whereas 63% of the patients with reflux oesophagitis had hernia. In patients without reflux oesophagitis the incidence of hiatus hernia was 8%. Reflux oesophagitis was significantly (p less than 0.001) related to hiatus hernia. The severity of the oesophagitis was significantly (p less than 0.05) related to the presence and the size of hernia, and severe oesophagitis without hernia was significantly (p less than 0.01) related to chronic alcoholism. The results suggest that a sliding hiatus hernia may play a role in the development of reflux oesophagitis.     

Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case-control study.

We conducted a case-control study in five general hospitals in the region of Antwerp, studying 161 patients (102 men, 59 women) and hospital control subjects matched for age and sex to explore the relation between drug use and upper gastrointestinal bleeding from 'erosive lesions' (peptic oesophagitis, gastric erosions, gastric ulcer(s), or duodenal ulcer(s]. There was a highly significant difference between cases and control subjects in the use of non-steroidal anti-inflammatory drugs (NSAIDs, excluding aspirin) (odds ratio 7.4, p less than 0.001; 95% confidence interval odds ratio 3.7 to 14.7). There also was a significant difference in the use of aspirin (odds ratio 2.2, p = 0.025; 95% CI odds ratio 1.3 to 4.0) and a highly significant difference regarding the presence of antecedents of peptic ulcer disease (odds ratio 5.5, p less than 0.001; 95% CI odds ratio 3.2 to 9.6). There was no significant difference in the use of other drugs, paracetamol and corticosteroids in particular, nor in the use of alcohol or tobacco. The patient group using NSAIDs was older, had more women, and had a higher mortality than the group not using NSAIDs. Among patients with bleeding gastric or duodenal ulcer(s), NSAID users were not more or less likely to have had symptoms of peptic ulcer disease, and had no higher frequency of multiple gastric or duodenal ulcers. The attributable risk for NSAID use was 0.30 (95% CI 0.23 to 0.37) and for aspirin use 0.14 (95% CI 0.08 to 0.20).     

Sex differences in risk factor control of treated hypertensives: a national primary healthcare-based study in Sweden.

BACKGROUND: To evaluate potential sex differences, this study aimed to investigate blood pressure and lipid control and other risk factors for cardiovascular disease in treated hypertensive (tHT) patients from primary healthcare. DESIGN AND METHODS: This cross-sectional survey of tHT patients was carried out between 2002 and 2005 by 264 primary care physicians from Sweden who consecutively recruited 6537 tHT patients (48% men and 52% women) from medical records. RESULTS: tHT men more often reached the treatment goal for systolic/diastolic blood pressure, less than 140/90 mmHg, than tHT women (30 vs. 26%, P<0.01). Men had lower systolic blood pressure than women, however, women had lower diastolic blood pressure and higher pulse pressure. More tHT women had total cholesterol>or=5.0 mmol/l than corresponding men (75 vs. 64% P<0.001). Men more often had diabetes (25 vs. 20% P<0.001), left ventricular hypertrophy (20 vs. 16% P<0.001), and microalbuminuria (24 vs. 16% P<0.001). Women were more often treated with diuretics (64 vs. 48%) and beta-receptor blockers (54 vs. 51%), and men more often treated with angiotensin-converting enzyme inhibitors (27 vs. 18%), calcium channel blockers (34 vs. 26%), and lipid-lowering drugs (34 vs. 29%). CONCLUSION: A need still exists for more intensified treatment of elevated blood pressure and hypercholesterolemia, especially in women. In hypertensives of both sexes, smoking and other risk factors also need to be addressed to reduce the risk of cardiovascular disease.     

Effect of famotidine on oesophageal sensitivity in gastro-oesophageal reflux disease.

Gastric acid suppression could improve heartburn by healing oesophagitis or by reduction of oesophageal sensitivity to acid. To independently assess changes in oesophageal sensitivity, it would be necessary to study patients with reflux disease but no oesophagitis. The aim of this study was to investigate the effect of acid suppression on oesophageal sensitivity and to assess the time course of any measured effect. Twenty seven patients were recruited, of whom 25 completed the study (14 men and 11 women, mean (SD) age 50 (15) years). All had classic symptoms of gastro-oesophageal reflux but normal results of upper gastrointestinal endoscopy and oesophageal mucosal histological tests. Each had abnormal 24 hour pH studies and a positive acid perfusion tests. Subjects were assigned double blind to placebo (n = 11) or famotidine 40 mg twice daily (n = 14) for four weeks. Acid perfusion tests were carried out at 0, 4, 5, and 8 weeks and time to heartburn recorded. Time to heartburn (mean (SEM)) was 124 (78) seconds in the famotidine and 187 (154) in the placebo group at week 0 (NS). Compared with baseline, significant increases in time to heartburn was found with famotidine at weeks 4 (383 (102), p < 0.01) and 5 (344 (92), p < 0.01) but not week 8 (336 (90) seconds). No significant effects were found with placebo (219 (41), 146 (23), and 144 (25) seconds for weeks 4, 5, and 8). Heartburn symptom score decreased significantly with famotidine (mean scores 3.6, 1.9, 2.1, and 2.6 at weeks 0, 4, 5, and 8 (p=0.001)) and showed a significant negative correlation with time to heartburn (r(s)=-0.60; p<0.0001). It is concluded that oesophageal sensitivity to acid is reduced by famotidine independent of and effect on oesophagitis; the effect wanes one to four weeks after the end of treatment and correlates with change in heartburn score.     

Healing of grade-II and III oesophagitis through motility stimulation with cisapride

The clinical relevance of cispride's stimulating effects on lower oesophageal motility was studied in 19 patients with documented (endoscopy, biopsy) grade II or III oesophagitis. Patients were treated for 8 or 16 weeks (depending essentially on whether the result was cure or failure) with 10 mg of cisapride four times a day (n = 11) or placebo (n = 8). Cisapride was superior to placebo with regard to mucosal healing (p less than 0.001) and symptomatic improvement (p less than 0.05): at the end of treatment, healing (grade 0) was observed in 8 cisapride patients, against 1 placebo patient, and reflux symptoms had disappeared in 7 and 1 patients, respectively. In conclusion, cisapride was of significant benefit to oesophagitis patients and was well tolerated.     

Frequency of mandibular dysfunction symptoms in institutionalized elderly people.

Mandibular dysfunction symptoms were found in 74% of 375 elderly persons, aged 65 or over, 79% of the women and 59% of the men (p less than 0.001). 36% had one symptom, 26% two symptoms, 8.5% three symptoms, and 3% 4--5 symptoms. The most frequent were the temporomandibular joint (TMJ) sounds (48%). Deviation of mandible on opening and/or closing movement was found in 44%, in women more often than men (p less than 0.05). The frequency of limited opening was 14%, higher among women than men (p less than 0.05). Tenderness to palpation laterally over the TMJ was observed in 14%. 7% reported pain on opening movement, women more often than men (p less than 0.01).     

Is ineffective oesophageal motility associated with reflux oesophagitis?

OBJECTIVE: To evaluate the association between ineffective oesophageal motility and reflux oesophagitis controlling for hiatal hernia, hypotensive lower oesophageal sphincter and male sex in patients with gastro-oesophageal reflux disease. METHODS: A total of 387 patients with reflux disease (mean age, 46 years, 42% men) were consecutively selected from a database. All patients underwent upper endoscopy, oesophageal manometry and 24 h oesophageal pH-metry in accordance with a standardized protocol. Reflux disease was confirmed either by endoscopy (oesophagitis grade I-IV according to Savary-Miller) or by pH-metry (increased acid exposure). Hiatal hernia was diagnosed endoscopically, whereas ineffective oesophageal motility and hypotensive lower oesophageal sphincter were characterized during manometry testing. The association between ineffective oesophageal motility and reflux oesophagitis was assessed by logistic regression analysis. RESULTS: A total of 166 patients with oesophagitis (mean age 45 years, 49% men) and 221 without oesophagitis (mean age 46 years, 37% men) were present. Prevalences of ineffective oesophageal motility, hiatal hernia, hypotensive lower oesophageal sphincter and male sex were significantly higher in patients with oesophagitis compared with those without oesophagitis (P<0.05). Ineffective oesophageal motility was independently associated with oesophagitis after multivariate logistic regression analysis (odds ratio=1.68; 95% confidence interval=1.04-2.70). CONCLUSION: Ineffective oesophageal motility is associated with reflux oesophagitis, independently of hiatal hernia, hypotensive lower oesophageal sphincter and male sex.     

Age- and gender-related changes in exercise left ventricular function in mitral valve prolapse

The correlates of exercise left ventricular (LV) performance were examined in 45 patients with isolated mitral valve prolapse (no associated mitral regurgitation or coronary artery disease). There were 18 men and 27 women, aged 16 to 73 years; 20 patients were 40 years or younger and 25 were older than 40. The response of the LV ejection fraction (EF) to symptom-limited upright exercise was normal (at least a 5% increase) in 27 patients (60%) and abnormal in 18 (40%). There were no significant differences between patients with normal and abnormal EF response in clinical presentation, electrocardiographic findings (at rest or during exercise), medications, rest EF, heart rate (at rest or during exercise) and systemic arterial pressure (at rest and during exercise). A normal EF response was observed more frequently in patients 40 years or younger than in those older than 40 (80 vs 44%, p less than 0.01), and more often in men than in women (78 vs 48%, p less than 0.04). The change in EF from rest to exercise was 18 +/- 9% in men and 5 +/- 10% in women 40 years or younger (p less than 0.01), and 9 +/- 8% in men and 2 +/- 8% in women older than 40 (p less than 0.04). Thus, patients (especially women and those older than 40 years) with isolated mitral valve prolapse may have abnormal LV functional reserve. Genetic differences in the expression of the disease in both sexes and age-related irreversible myocardial changes may explain these observations.