[Show abstract][Hide abstract] ABSTRACT: Background:
Lamin A/C (LMNA) mutation carriers suffer from a variety of clinical phenotypes, including dilated cardiomyopathy (DCM). Although it has been suggested that carriers are at risk for thromboembolic complications, it is unknown whether this risk is higher than can be expected from the underlying cardiac abnormalities. The purpose of this study was to determine whether a LMNA mutation is associated with an increased risk of thromboembolic complications.
We compared a cohort of 76 LMNA mutation carriers with a cohort of 224 idiopathic DCM patients without a LMNA mutation, with respect to the prevalence of arterial and venous thromboembolic complications. Furthermore, we carried out a case-control study to explore whether a prothrombotic phenotype was present in LMNA mutation carriers without DCM or atrial tachyarrhythmias (n=14) and compared this with mutation negative relatives (n=13).
The prevalence of thromboembolic complications was higher in the cohort of LMNA mutation carriers than in DCM patients (22 vs 11%; p<0.05), after respectively mean follow-up of 42 ± 12 and 49 ± 12 years. After adjustment for possible confounders, including atrial tachyarrhythmias and left ventricular ejection fraction, LMNA mutation carriership was independently associated with an increased risk of thromboembolic complications (HR 4.8, 95% CI: 2.2-10.6). The results of the case-control study suggested a prothrombotic phenotype in LMNA mutation carriers, as reflected by an altered platelet function and increased thrombin generation.
LMNA mutation is independently associated with an increased risk of arterial and venous thromboembolic complications. Laboratory research in LMNA mutation carriers without severe cardiac abnormalities suggests a prothrombotic phenotype.
International journal of cardiology 10/2012; 168(1). DOI:10.1016/j.ijcard.2012.09.118 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A positive family history of premature coronary artery disease (CAD) is a risk factor for cardiovascular disease (CVD), independent of traditional risk factors. Therefore, currently used risk algorithms poorly predict risk in these individuals. Novel methods are thus needed to assess cardiovascular risk. Pulse-wave velocity (PWV) might be such a method, but it is unknown whether PWV is increased in first-degree relatives of patients with premature CAD.
Observational case-control study.
Patients with premature CAD and a positive family history of premature CVD (n=50), their first-degree relatives without CVD (n=50) and unrelated controls (n=50).
PWV was measured with using an Arteriograph system. Differences in PWV were assessed by a generalised linear model and multinomial logistic regression.
Patients with premature CAD had a higher PWV compared with first-degree relatives and controls (9.69±2.90 m/s vs 8.15±1.96 m/s and 7.38±1.08 m/s; p<0.05 patients vs all groups). Linear regression showed all groups related to PWV, with patients having the highest PWV and controls the lowest (p<0.0001). Furthermore, PWV was associated with first-degree relatives (OR 1.32, 95% CI 1.02 to 1.72; p<0.05) and premature CAD (OR 1.72, 95% CI 1.32 to 2.24; p<0.05) compared with controls. These findings were independent of blood pressure and other traditional risk factors.
Patients with premature CAD and their first-degree relatives had higher PWV compared with controls, independent of other risk factors. This holds promise for the future, in which arterial stiffness might play a role in risk prediction within families with premature CAD.
[Show abstract][Hide abstract] ABSTRACT: Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls.
In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts.
Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective study.
PLoS ONE 10/2011; 6(10):e25946. DOI:10.1371/journal.pone.0025946 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Long QT syndrome (LQTS), a potentially fatal disorder, has to be distinguished from non-fatal conditions. Our aim was to investigate whether history-taking can be used in identifying patients likely to have LQTS.
We compared the characteristics of a group of LQTS patients with syncope patients presenting at the emergency department (ED) and vasovagal patients younger than 40 years of age. Thirty-two LQTS patients were included. We included 113 patients at the ED and 69 vasovagal patients. Family history of syncope, sudden cardiac death, or cardiovascular disease was found more often in LQTS patients. Palpitations were the only symptom reported more often in this group. Syncope while supine, during emotional stress and associated with exercise was also more common among LQTS. Standing as a trigger was found more often in ED and vasovagal patients.
We conclude that a family history for syncope and sudden cardiac death, palpitations as a symptom, supine syncope, syncope associated with exercise, and emotional stress place patients at higher risk for LQTS. These findings should alert physicians to the potentially life-threatening illness of LQTS, and act accordingly by obtaining an electrocardiogram and paying specific attention to the QT interval.