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Increased carotid plaque burden in men with the Fibrillin-1 2/3 genotype
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
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2014 (English)In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 41, no 9, 637-642 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Fibrillin-1 is an important constituent of the vascular wall and earlier studies have indicated an effect of the Fibrillin-1 (FBN1) 2/3 genotype on blood pressure as well as aortic stiffness in men. The aim was to determine if the FBN1 2/3 genotype was associated with presence of carotid plaque and incident cardiovascular morbidity and mortality in middle-aged subjects.

Material and Method: The FBN1 genotype was characterized in 5765 subjects (2424 men, 3341 women; aged 45-69 years) recruited from the Malmö Diet and Cancer Study Cardiovascular Cohort, Sweden. Plaque occurrence and intima media thickness (IMT) of the carotid artery were assessed by ultrasound. Incidence of first cardiovascular events (myocardial infarction and stroke) and cause-specific mortality was monitored during a mean of 13.2 years follow-up.

Results: The most common FBN1 genotypes were 2/2, 2/3 and 2/4 which accounted for 92.2% (n=5317) of the subjects. There were no differences between the three genotypes regarding age, blood pressure, glucose, lipids, smoking habits, CCA diameter and IMT in men and women. Presence of plaque in the carotid artery was higher in men with genotype 2/3 as compared to the 2/2 and 2/4 genotypes, (55% vs. 46% and 50%, p=0.007). No similar difference was observed in women. No significant relationship was observed between FBN1 genotypes and incidence of CVD or all-cause mortality.

Conclusions: The increased prevalence of plaque in the carotid artery of middle-aged men with FBN1 2/3 genotype indicates a pathological arterial wall remodeling with a more pronounced atherosclerotic burden. 

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014. Vol. 41, no 9, 637-642 p.
Keyword [en]
IMT, cardiovascular risk, blood pressure, arterial wall, human
National Category
Physiology
Identifiers
URN: urn:nbn:se:liu:diva-86143DOI: 10.1111/1440-1681.12259ISI: 000344348100004PubMedID: 24837032OAI: oai:DiVA.org:liu-86143DiVA: diva2:574997
Available from: 2012-12-07 Created: 2012-12-07 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Influence of Genetics and Mechanical Properties on Large Arteries in Man
Open this publication in new window or tab >>Influence of Genetics and Mechanical Properties on Large Arteries in Man
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Arterial pathology is the major contributor to cardiovascular diseases and mortality. The mechanical properties of arteries are independent factors for cardiovascular disease and mortality, where genetics influence the structure of the arterial wall, which may result in change in arterial stiffness. The aims of this thesis were to study the mechanical properties of the popliteal artery (PA) in healthy subjects and the influence of angiotensin-converting enzyme (ACE) polymorphism and Fibrillin-1 (FBN1) polymorphism on large arteries. Further, the impact of FBN1 polymorphism on cardiovascular morbidity and mortality was investigated.

The PA is, after the abdominal aorta, the most common site of aneurysmal development. The PA was studied in healthy subject with ultrasound and the diameter increased and the distensibility decreased with age, with men having lower distensibility than women. This seems not to be the behavior of a true muscular artery but rather of a central elastic artery such as the aorta, and might have implications for the susceptibility to aneurysm formation, as well as the association of dilating disease between the PA and the aorta. The wall stress in the PA was low and unaffected by age, probably caused by a compensatory remodeling response with an increase in wall thickness. This indicates that other mechanisms than wall stress contribute to the process of pathological dilatation in the PA.

The ACE D allele may be associated with abdominal aortic aneurysm. Elderly men with the ACE D allele were associated with increased abdominal aortic stiffness compared to men carrying the I/I genotype. This suggests that the ACE D allele impairs arterial wall integrity, and in combination with local hemodynamic and other genetic factors it may have a roll in aneurysm formation.

The FBN1 2/3 genotype has been associated with increased systolic blood pressure. The FBN1 2/3 genotype in middle-aged men was associated with increased abdominal aortic stiffness and blood pressure which indicates an increased risk for developing cardiovascular disease. The increased presence of plaque in the carotid artery of middle-aged men with the FBN1 2/3 genotype indicates a pathological arterial wall remodeling with a more pronounced atherosclerotic burden, but did however not affect the risk of cardiovascular events and/or death in this population. This relationship needs to be studied further.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 77 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1340
National Category
Physiology
Identifiers
urn:nbn:se:liu:diva-86144 (URN)978-91-7519-761-6 (ISBN)
Public defence
2013-01-25, Orginalet, Qulturum, Hus B4, , Länssjukhuset Ryhov, Jönköping, 09:00 (Swedish)
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Available from: 2012-12-07 Created: 2012-12-07 Last updated: 2017-03-27Bibliographically approved

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De Basso, RachelLänne, Toste

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