BMJ  2003;327:591-592 (13 September), doi:10.1136/bmj.327.7415.591

Paper

Preclinical coronary atherosclerosis in a population with low incidence of myocardial infarction: cross sectional autopsy study

¹ Institut de Medicina Legal de Catalunya, C Prim 32-40, Badalona, E-08911, Spain, ² Hospital Sant Jaume, C Sant Jaume 209-217, Calella (Barcelona), E-08370, Spain, ³ Centro Nacional de Investigaciones Oncológicas, C Melcho r Fernández Almagro 3, Madrid, E-28029, Spain, ⁴ Hospital Municipal de Badalona, Via Augusta 9-13, Badalona, E-0 8911, Spain, ⁵ Departamento de Farmacología, Facultad de Farmacia, Univ ersitat de Barcelona, Diagonal 643, Barcelona, E-08028, Spain, ⁶ Unidad de Lípidos, Servicio de Nutrición y Dietética, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, C Villarroel 170, Barcelona, E-08036, Spain

Introduction

Studies of autopsies indicate that atherosclerosis begins in childhood and is related to risk factors for coronary heart disease in the same way as for adult atherosclerosis.¹ In Spain, despite risk factors for coronary heart disease being common, incidence of myocardial infarction and related mortality rates are among the lowest in the world.^{2 3} This paradox may be explained in two ways. One theory proposes that there is a time lag between increased consumption of animal fat and raised serum cholesterol concentrations, which have occurred more recently in Mediterranean populations than in other Western countries, and the expected increase in rates of coronary heart disease.⁴ An alternative explanation is that Mediterranean countries share behavioural and socioeconomic factors that prevent or delay atherogenesis.⁵ If this is true, the arteries of young Spaniards should be free from atheroma. We studied autopsies to evaluate the prevalence and severity of atherosclerosis in several arterial beds of young trauma victims from Barcelona. We report the results of left coronary artery evaluation.

Participants, methods, and results

At four forensic laboratories in Barcelona we consecutively collected specimens from 65 young and healthy people (50 men and 15 women) aged 12-35 years who died of external causes. We measured thiocyanate in postmortem serum by spectrophotometry (an objective measure of smoking), and we determined lipoprotein cholesterol with an enzymatic method. We measured the circumference of the waist and hips, and we analysed subcutaneous abdominal adipose tissue by gas chromatography for fatty acids.

After weighing the heart, we dissected the left coronary artery and stained 3 µm transverse sections embedded in paraffin with haematoxylin eosin. We graded the severity of atherosclerotic lesions microscopically using the criteria of the American Heart Association.¹ We used ² tests, Fisher's exact test, or unpaired t tests with a 5% alpha risk to examine whether atherosclerosis was related to age and if severity of lesions was associated to risk factors.

Mean age was 24 years, and 33 (51%) were smokers. Mean waist to hip ratio, heart weight, and cholesterol concentration (0.84, 327 g, and 4.42 mmol/l) were within 95% confidence intervals of reference values.³

Fibrous plaques were present in 17 (34%; 95% confidence interval 21% to 49%) men but were absent (0; 0% to 22%) in women. Compared with the 33 men without plaques, the 17 men with plaques were on average 6 years older (P < 0.001) and had significantly higher serum total cholesterol (by 0.76 mmol/l) and very low density lipoprotein cholesterol (by 0.27 mmol/l) (P < 0.05 for both) (figure). Measures of adiposity, smoking behaviour, and the fatty acids in adipose tissue were similar in men with and without plaques.

View larger version (24K): [in this window] [in a new window]   Prevalence of atherosclerotic lesion in the left coronary artery of 65 young Spanish trauma victims according to age; fibrous plaques are more likely with increasing age (2=13.78, P=0.003); grade 1—isolated intimal foam cells, minimal changes; grade 2—numerous intimal foam cells often in layers, fatty streaks; grade 3—pools of extracellular lipid without a well defined core, intermediate lesions, or preatheroma; grade 4—well defined lipid cores with a luminal surface covered by normal intima, atheroma, or fibrous plaques; grade 5—lipid cores with a fibrous cap with or without calcification, fibroatheroma; grade 6—fibroatheroma with cap defects such as haemorrhage or thrombosis, complicated lesions (we did not find lesions of grades 5 or 6)

 

Comment

We found unexpectedly high numbers of plaques in young Spanish men, similar to the prevalence in populations with much higher rates of coronary heart disease,¹ for Barcelona, a geographical location with low incidence of myocardial infarction.² The most advanced lesions were fibrous plaques—that is, stable atheroma—and not the vulnerable plaques that underlie acute coronary syndromes and which rupture easily. The decreasing prevalence of fatty streaks and the increasing rates of more advanced lesions with age suggests a temporal progression of lesion severity (figure). Abnormal blood lipids were associated with coronary plaques.¹

Morbidity and mortality from myocardial infarction are low in Spain,² but angina is as common as in Western countries with higher rates of coronary heart disease.³ In Spain, coronary atherosclerosis evolves more slowly. Although a time lag to increased rates of coronary heart disease could be approaching its end,⁴ unknown protective factors might also prevent coronary plaques from becoming unstable in this population.

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Details of the study group are on bmj.com

We thank M Vaquero for dissecting the coronary arteries; J C Borondo for pathologic evaluations; R Llombart for collecting anatomical specimens; E Casals for supervising biochemical analyses; D Zambon for support in statistical analysis; M Guevara and C Bauchet for lipoprotein and thiocyanate determinations; Instituto Anatómico Forense, Barcelona; and J Marrugat for reviewing the manuscript.

Contributors: AB, ER, and OGV conceived and designed the study. OGV and XF processed the histological samples of the coronary arteries and scored the lesions. MV and JCL processed and interpreted measurements of fatty acids in adipose tissue. AG, XF, and ER analysed and interpreted the data. AB and ER drafted and revised the paper. AB and ER are guarantors. See bmj.com for details of the Estudio Forense de Aterosclerosis Preclínica study group.

Funding: Spanish Health Ministry, FIS 96/2006.

Competing interests: None declared.

Ethical approval: Not required.

References

1. McGill HC Jr, McMahan CA, Herderick EE, Malcom GT, Tracy RE, Strong JP. Origin of atherosclerosis in childhood and adolescence. Am J Clin Nutr 2000; 72(suppl): 1307-15S.
2. Tunstall-Pedoe H, Vanuzzo D, Hobbs M, Mahonen M, Cepaitis Z, Kuulasmaa K, et al. Estimation of contribution of changes in coronary care to improving survival, event rates, and coronary heart disease mortality across the WHO MONICA Project populations. Lancet 2000; 355: 688-700.[CrossRef][Web of Science][Medline]
3. Villar Álvarez F, Banegas Banegas JR, Donado Campos JM, Rodríguez Artalejo F. Las enfermedades cardiovasculares y sus factores de riesgo en España: hechos y cifras. Informe SEA 2003 [Cardiovascular diseases and their risk factors in Spain: facts and figures: a report from the Spanish Atherosclerosis Society 2003]. Madrid: Ergon, 2003. (In Spanish.)
4. Law M, Wald N. Why heart disease mortality is low in France: the time lag explanation. BMJ 1999; 318: 1471-80.[Free Full Text]
5. Marrugat J, Masiá R, Elosua R, Covas MI. Cardiovascular protective factors: can they explain for differences in mortality and morbidity between the Mediterranean and the Anglo-Saxon population? Cardiovasc Risk Factors 1998; 9: 196-204.

(Accepted July 15, 2003)

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