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- Goel, Kashish, et al.
(författare)
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Novel Cyp2C19 Genetic Variants associated with Stent Thrombosis : a Next Generation Sequencing Study
- 2018
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 71:11, s. 1205-1205
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCommonly tested Loss-of-function (LOF) alleles in CYP2C19 are present in 30-40% of patients who experience stent thrombosis. The objective of this study was to identify novel genetic variants in CYP2C19 gene associated with stent thrombosis.MethodsWe included 70 patients with definite stent thrombosis while on clopidogrel who had stored DNA samples in our institutional (n=12) or PLATO trial (n=70) biorepository. Cases were matched 1:1 with controls for age, race, sex, diabetes, type of stent, and presentation. All controls were on clopidogrel and free of recurrent events. Clinical Pharmacogenetics (PGx) Implementation Consortium (CPIC) guidelines were used to determine the list of known PGx variants and dbSNP version 142 was used to assess novel variants. Whole exome sequencing was performed using the protocol for Agilent's SureSelect Human All Exon v5 + UTRs 75 MB kit and additional custom primers were designed to cover the entire CYP2C19 gene.ResultsMean age was 63 ± 12 years, and 71% were male. We identified a total of 456 single nucleotide variants (SNV) in the CYP2C19 gene (cases: 376; controls: 288), of which 5 were synonymous, 6 non-synonymous, 46 indels and 449 intronic SNVs. There were 168 vs. 80 novel CYP2C19 variants and 10 vs. 5 indels in cases vs. controls, respectively. Four SNVs (3 missense and 1 synonymous) were present only in cases, whereas 3 SNVs (1 misssense, 1 synonymous and 1 intron) were unique to controls. There were no detectable differences in the frequency of LOF CYP2C19*2 allele (cases 34% vs. controls 31%) or other CPIC annotated PGx variants in cases and controls. After excluding the known PGx variants, there were 10 indels (all intronic) out of which 7 were novel in cases and were not present in controls.ConclusionWe describe several novel genetic variants in the CYP2C19 gene in patients treated with clopidogrel after coronary stenting. We identified 168 novel SNVs and 10 novel indels in the CYP2C19 gene of patients with stent thrombosis. Four SNVs and 9 indels were unique to cases. Functional validation of these CYP2C19 genetic variants may provide important insights of CYP2C19 and the pathophysiology of stent thrombosis in clopidogrel treated patients.
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- Hagstrom, Emil, et al.
(författare)
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IMPACT OF BODY WEIGHT AT AGE 20 AND WEIGHT GAIN DURING ADULTHOOD ON MIDLIFE CORONARY ARTERY CALCIUM IN 15,000 MEN AND WOMEN : AN INTERIM ANALYSIS OF THE SWEDISH CARDIOPULMONARY BIOIMAGE STUDY
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 1692-1692
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundElevated body weight in adolescence is strongly associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, or to weight gain with subsequent high adult weight is not known. Using data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), we investigated the association between weight at age 20, weight gain to midlife and coronary artery calcium score (CACS) at midlife.MethodsIn the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on CACS at midlife, self-reported body weight at age 20 and weight at examination in SCAPIS were recorded.ResultsCACS in midlife was significantly higher with increasing weight at age 20 (p<0.001 for both sexes), and then increased with weight gain until midlife at all levels of body weight at age 20 after adjusting for age, height, smoking, alcohol intake, education level, exercise levels and LDL cholesterol. However, the association with weight gain was only significant in men (p = 0.047), not in women (p=0.474). No significant interaction was seen between weight at age 20 and midlife weight with CACS. The effect of weight at age 20 on CACS was significantly more marked in men than in women, as was the effect of weight gain (p<0.001 for both interactions).ConclusionWeight at age 20 and weight gain to midlife were both related to CACS, but much more markedly so in men than in women, indicating a generally larger effect of both early adult weight and further weight gain until midlife on CACS in men, compared to women.
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- Norlund, Fredrika, et al.
(författare)
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Web-Based Cognitive Behavior Therapy for Depression and Anxiety among Patients with a recent Myocardial Infarction : The U-CARE Heart Randomized Trial
- 2018
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 71:11, s. 1884-1884
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundSymptoms of depression and anxiety are common after a myocardial infarction (MI). Web-based cognitive behavioral therapy (wCBT) may improve access to effective psychological treatment to reduce these symptoms. The aim of this prospective randomized trial was to evaluate the effectiveness of a wCBT intervention to reduce self-reported symptoms of depression and anxiety among patients with a recent MI.MethodsIn total, 3928 patients were assessed for eligibility in routine care setting at 25 hospitals. Of these, 239 patients (33% women, mean age 60 years) with a recent MI (< 3 months) and symptoms of depression and/or anxiety assessed with Hospital Anxiety and Depression Scale (HADS) were randomly allocated to a therapist-supported 14 week wCBT program (n=117) or standard of care (n=122). The wCBT program was a tailored intervention with 10 different eligible modules, especially designed for MI patients. Treatment was evaluated according to the intention-to-treat principle. The primary outcome was group difference in HADS total score (HADS-T) at follow-up. Multiple imputation was performed. The pooled treatment effect was thereafter estimated in a multiple linear model, controlling for baseline HADS, age and sex.ResultsThere was a reduction in HADS-T over time in the total study sample (delta = -5.1; P < .0001). The difference at follow-up between the wCBT group and the control group with regard to HADS-T was non-significant (-0.47, [-1.95, 1.00], P=0.53). Treatment adherence was low. In the treatment group, 54% completed the introductory module and 15% completed additional modules.ConclusionThis wCBT program did not reduce symptoms of depression and/or anxiety in post-MI patients as compared to standard of care. Low treatment adherence was observed and reasons for this needs to be further explored.
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