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Background: Mutations in the cardiac β-myosin heavy chain (MYH7) and cardiac troponin T (TNNT2) genes are reportedly responsible for up to 40% of familial cases with hypertrophic cardiomyopathy (HC). Although there are no mutational hotspots, most of the mutations are located in specific exons of the MYH7 and TNNT2 genes. Currently it is not possible to predict the phenotype in carriers of mutations in these genes, although it is widely accepted that mutations in the MYH7 gene predispose to severe HC, whereas TNNT2 mutations are frequently linked to sudden cardiac death (SCD) in spite of minimal hypertrophy. Methods: We sequenced exons 8, 9, 13–16, 19, 20, 22–24, and 30 of the MYH7 gene and exons 8, 9, 11, and 14–16 of the TNNT2 gene in 30 HC patients (18–60 years of age) from the region of Asturias (Northern Spain); 25 cases (80%) had a family history of the disease. Genomic DNA was amplified, and fragments were directly sequenced. Each DNA variant found in the patients was also analyzed in 200 healthy controls through single-strand conformation analysis. Results: Four of the probands had nucleotide changes absent in the healthy controls. Two cases had mutations previously described in the MYH7 gene (exon 14, Arg453Cys) or the TNNT2 gene (exon 16, Arg278Cys). Two cases had new mutations (MYH7 exon 22, Met822Val; TNNT2 exon 14, Lys247Arg) not found among the healthy controls. We found MYH7 Met822Val in a woman with a severe form of HC; the mutation was absent in her parents, indicating a de novo mutation. MYH7 R453C was present in a woman with mild HC, mother of a son who died from SCD. TNNT2 R278C was present in a woman with severe HC, but a sister and a daughter were mutation carriers and did not have hypertrophy. A patient with severe HC was carrier of TNNT2 247Arg. Conclusions:Mutations in the MYH7 and TNNT2 genes can be found in patients without a family history of HC. However, compared with other populations MYH7 or TNNT2 mutations were rare among our HC patients. This study illustrates the extreme phenotypic heterogeneity in carriers of MYH7 or TNNT2 mutations.

In order to determine the role of two polymorphisms in the factor VII gene (R353Q and intron 7 hypervariable region) in the susceptibility to develop early myocardial infarction, a total of 175 patients with acute myocardial infarction aged 50 years or less (mean age 41±7 years) and 200 controls (average age 42±6) without cardiovascular disease were genotyped for these polymorphisms. Gene and genotype frequencies did not differ between patients and controls. Although the 353-QQ genotype was at a higher frequency among controls (4%) compared to patients (1%), the difference did not reach statistical significance. Carriers of the H7-allele (intron 7 polymorphism) were at a slightly higher frequency among patients (51 vs. 43%; P =0.19; OR=1.36; 95% CI=1.09–1.70). Our data suggest a lack of association between both polymorphisms in the factor VII gene and early myocardial infarction in our population.

Objetivo Analizar la relacion de las concentraciones sericas de lipoproteina (a) con la edad de presentacion de la cardiopatia isquemica y la severidad angiografica de la enfermedad coronaria en un grupo de varones menores de 50 anos. Pacientes y metodos Hemos estudiado a un grupo de 230 varones menores de 50 anos, que fueron ingresados de forma consecutiva por un sindrome coronario agudo. Durante su ingreso, se determinaron las concentraciones de lipoproteina (a) a todos los pacientes, los cuales fueron distribuidos en dos grupos segun la edad de aparicion de enfermedad coronaria, con un punto de corte de 40 anos. Se realizo un cateterismo cardiaco a 142 pacientes por mal control clinico o isquemia persistente. Resultados Las concentraciones sericas de lipoproteina (a) se relacionaron con el numero de vasos coronarios afectados; asi, en la coronariografia normal los valores fueron de 12 mg/dl (1,5-75), en la enfermedad de un vaso de 27 mg/dl (2,5-96), en la enfermedad de dos vasos de 34 mg/dl (7-90) y en la enfermedad de tres vasos de 63 mg/dl (2-116), con significacion estadistica (p = 0,003). No encontramos diferencias significativas en las concentraciones de lipoproteina (a) al analizar la edad de presentacion de las primeras manifestaciones clinicas, resultando de 31 mg/dl (2-97) en pacientes de 40 anos o menos y de 33 mg/dl (2-94) en mayores de 40 anos. Conclusiones En nuestro grupo de varones con inicio clinico de enfermedad coronaria antes de los 50 anos hemos encontrado una relacion entre las concentraciones de lipoproteina (a) y la severidad angiografica de la enfermedad coronaria. Sin embargo, no hemos encontrado relacion entre las concentraciones de lipoproteina (a) y la edad de presentacion de la enfermedad coronaria.

The prevalence of angiographically normal corsomeone more lession.70%; 95normal coronary onary arteries in patients with early coronary disease angiogram. has been difficult to determine because some reports The results are summarized in Table 1. [1,2] have included patients with up to 50% coronary In 87 patients (61%) the lesion was located in the stenosis as well as those free of lumen narrowing. left anterior descending artery. The circumflex Others have distinguished patients with moderate showed lesions in sixty patients (42%) and the right disease from those with normal arteries [3,4]. Howcoronary in seventy-nine patients (55%). We diagever, prospective and retrospective analyses [1–6] of nosed left main coronary artery disease in eight patients with ischemic heart disease at a young age patients (5%). have described angiographically normal coronary In our study with male with early-onset of isarteries in 9–17%. chemic heart disease, we found normal coronary In order to determine the angiographic characterisangiography in 10% of myocardial infarctions. The tics in the early symptomatic coronary artery disease, left anterior descending was the artery more frequentwe studied 142 patients admitted to the coronary care ly affected and isolated left main coronary disease unit by acute myocardial infarction or unstable angina was an infrequent finding. with electrocardiographic ischaemic changes. These patients were prospectively evaluated (mean age 4365) and all of them underwent a coronariographic Table1 study. We decide to score as follow: 15one vessel Angiographic findings stenosis.70%; 25two vessels stenosis.70%; 35 Score n % Infarction Angina three vessels stenosis.70%; 45milking; 55isolated (%) (%) left main coronary artery disease; 65left main cor1 45 32 35 29 onary artery disease and someone more vessel; 75 2 31 22 26 19 isolated vessel stenosis#70%; 85stenosis#70% and 3 23 16 11 20 4 2 1.5 0 2.5 5 3 2 0 3.5 6 5 3.5 0 6 7 5 3.5 5 2.5 *Corresponding author. Tel.: 134-985-091-157; fax: 134-985-0918 15 10.5 13 9.5 157. 9 13 9 10 8 E-mail address: abatalla@telecable.es (A. Batalla).

We present the case of a healthy young white man, who suddenly complained of strong pain in the lower extremities while he was cycling. An emergency bilateral femoral thromboembolectomy was carried out and thrombotic material was obtained. A two-dimensional echocardiogram showed a mobile mass adhered to the apex. Pathological study of the mass revealed a small myocardial infarction with thrombus.

The nature of changes in the lipid profile caused by an acute infection is controversial. The aims of the present study were to study the changes in plasma lipids and lipoproteins in community-acquired pneumonia, to determine whether these changes differ according to the aetiologica/agents, and finally to observe the behaviour of these lipoproteins six months later. Sixty patients, aged between 18 and 87 years, admitted during the period September 1992 and April 1993 with suspected community-acquired pneumonia, were included in the study. Fifty-three of the patients completed the 15-day follow-up investigation, and 37 remained available for study for up to 6 months. On admission and at 15 and 180 days, analyses were carried out for total cholesterol, HDL cholesterol, apolipoproteins A1 and B, triacylglycerols and transaminases. Student's t test for parametric variables was used for statistical analysis, and the Mann-Whitney test for non-parametric variables. The concentrations of total cholesterol (4.2 +/- 1.0 vs 5.5 +/- 1.3 mmol/1), HDL cholesterol (0.9 +/- 0.4 vs 1.2 +/- 0.3 mmol/l), apolipoprotein A1 (0.80 +/- 0.25 vs 1.15 +/- 0.28 g/l) and apolipoprotein B (0.77 +/- 0.28 vs 0.95 +/- 0.28 g/l) showed significantly lower values during the acute infectious process. These analyte concentrations became stable after 15 days with the exception of HDL cholesterol which continued to increase until 6 months (1.2 +/- 0.3 vs 1.3 +/- 0.3 mmol/l, p < 0.01). Patients with non-viral atypical pneumonia showed, on admission, higher triacylglycerol values (1.8 +/- 0.8 vs 1.3 +/- 0.9 mmol/l, p < 0.01) and lower HDL cholesterol values (0.6 +/- 0.3 vs 1.0 +/- 0.4 mmol/l, p < 0.03). Values of aspartate aminotransferase (112 +/- 117 vs 23 +/- 11 U/l, p < 0.001), alanine aminotransferase (127 +/- 141 vs 24 +/- 16 U/l, p < 0.02) and gamma-glutamyl transferase (113 +/- 158 vs 33 +/- 25 U/l, p < 0.03) were higher in the subgroup of non-viral atypical pneumonia. In conclusion, patients with community-acquired pneumonia present a significant decline in total cholesterol, HDL cholesterol and apolipoprotein A1 and B concentrations. Lower concentrations of HDL cholesterol are maintained up 15 days. Patients with non-viral atypical pneumonia present on admission significantly higher triacylglycerol and lower HDL cholesterol values. Those with non-viral atypical pneumonia also present higher transaminase values.

activities, both the ECG (Fig. 1B) and Echo had 1. To the editor returned to normal. The 12-lead resting ECG helps clinicians to difMaking a distinction between physiological hyferentiate between both types of hypertrophy when is pertrophy that results from sustained training and normal. Experience shows that the ECG is normal in hypertrophic myocardiopathy is most of the time a most of the physiological hypertrophies [2,3]. Howdiagnostic problem. The challenge becomes greater in ever, hypertrophic cardiomyopathy has ECG abnorthose circumstances where the increase of cardiac malities more often [4]. mass diagnosed by echocardiography is accompanied Echocardiographic findings, such as the thickness by an abnormal electrocardiogram. In order to resolve of the walls and the study of ventricular diameters, this problem of diagnosis, some investigators have have been not sufficient in differentiating one type of proposed the reduction, and even the suppression, of hypertrophy from another, and the absence of outflow sports activities as an alternative method for distract obstruction makes the distinction between both tinguishing between these two kinds of hypertrophy types of hypertrophy more difficult [3]. Furthermore, [1]. study of the diastolic function by Doppler does not A 17-year-old male caucasian and asymptomatic provide more information, since 20% of carmountain-bike rider was sent to our Hospital as a diomyopathies have a normal diastolic pattern [5]. result of a pathological electrocardiogram. No familiFinally, molecular diagnosis has identified only al history of cardiac disease was evident. Physical 50% of mutations that produce hypertrophic carexamination and a chest X-ray were normal. The diomyopathy, and cardiac biopsies for research purelectrocardiogram (ECG) showed a 50 beats /min poses alone are controversial [6]. sinus rhythm, with negative T waves from V to V 1 4 The importance of ruling out a diagnosis of (Fig. 1A). These ECG abnormalities had been evident myocardiopathy in our subject with hypertrophy led two years before. The two-mode echocardiogram us to recommend a suppression of sports activities showed a concentric hypertrophy of the left ventricuand this resulted in a normalization of both the Echo lar wall. After three months cessation of sports and ECG. We conclude that electrocardiogram normalization after cessation of sports activities remains a useful tool for clinicians in those cases where differentiation *Corresponding author. Tel.: 134-985-09-1157; fax: 134-985-35-83between hypertrophic myocardiopathy and physiolog90. E-mail address: abatalla@telecable.es (A. Batalla). ical hypertrophy are difficult.

To the Editor: We have read with interest the report by Ardissino et al,[1][1] which concludes that the presence of the PlA2 polymorphic allele is the only prothrombotic genetic factor associated with the risk of myocardial infarction at a young age. These authors find a significant interaction

To the Editor: In a recent study published in your journal by Carter et al,1 strong evidence was found of an association between the PlA2 allele of the glycoprotein IIb/IIIa gene and myocardial infarction in men younger than 47 years old. In addition, a relationship of this polymorphism with cholesterol levels and the extent of coronary artery disease was also observed in multivariate analyses. Association of the PlA2 genotype and coronary disease is controversial. After the original study of Weiss et al2 reporting an association of PlA2 and coronary disease, others failed to find the same association.3 4 A study based on a population of 178 men younger than 50 years old and diagnosed …

In a recent study published in the Journal by Akosah et al. [(1)][1], the investigators found that the presence of borderline or mild hypercholesterolemia has significant effects on the development of premature coronary heart disease. In this way, a group of 229 male patients