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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Holmes, Michael V., et al.
(författare)
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Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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- Leusink, M., et al.
(författare)
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A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering
- 2016
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Ingår i: Pharmacogenomics. - : Future Medicine Ltd. - 1462-2416 .- 1744-8042. ; 17:6, s. 583-591
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome. Patients & methods: In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin response, following up associations with p < 1 × 10-4 (three independent studies, 5314 individuals). We further assessed the effect of a GRS based on SNPs in ABCG2, LPA and APOE. Results: No new SNPs were found associated with statin response. The GRS was associated with reduced statin response: 0.0394 mmol/l per allele (95% CI: 0.0171-0.0617, p = 5.37 × 10-4). Conclusion: The GRS was associated with statin response, but the small effect size (∼2% of the average low-density lipoprotein cholesterol reduction) limits applicability. © Future Medicine Ltd 2016.
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- Leusink, M., et al.
(författare)
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Cholesteryl Ester Transfer Protein Polymorphisms, Statin Use, and Their Impact on Cholesterol Levels and Cardiovascular Events
- 2014
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Ingår i: Clinical Pharmacology & Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 95:3, s. 314-320
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Tidskriftsartikel (refereegranskat)abstract
- The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin x SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 x 10-5) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.
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- Leusink, Peter, et al.
(författare)
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Vragen naar de onbekende weg. De seksuele anamnese in de medische praktijk [Sexual history-taking in medical practice: the elephant in the room?].
- 2016
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Ingår i: Nederlandsch tijdschrift voor geneeskunde. - : Bohn Stafleu van Loghum. - 0028-2162 .- 1876-8784. ; 160:A9896
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the Dutch College of General Practitioners released a Practice Guideline on Sexual Problems which provides clear directives for the diagnosis and management of various sexual disorders in men and women. Patients who are managed in general practice and in outpatient clinics might experience distress related to sexual problems due to their age, medical condition or treatment, or distress related to problems in establishing and maintaining intimate relationships. We present two clinical cases. The first case is a woman aged 44 years with breast cancer treated by mastectomy and adjuvant tamoxifen. The second case is a man aged 54 years with heart failure due to myocardial infarction and resultant loss of physical strength. Both cases illustrate that taking a short sexual history could result in the right treatment and patient satisfaction, without having to go into detail about very intimate and private matters.Case description The first case presents a woman, 44 years of age, with breast cancer treated by mastectomy and adjuvant tamoxifen. During follow up at the oncology clinic, she addressed complaints such as fatigue, mood swings, and sleep problems. The oncologist suspected a depressive disorder and referred the patient to the general practitioner (GP) in order to get support or treatment. The GP diagnosed a mild depressive disorder due to mild problems in her relationship caused by minimal emotional support from her partner. Treatment by a psychologist was advised but because its reimbursement was lacking, the patient decided to refrain. During consultation a year later, the oncology nurse practitioner asked her for her mood problems and asked whether sexual problems might cause her some burden. The patient was relieved to address her problems of decreased sexual desire and dyspareunia. The nurse gave education about the negative but reversible effect of tamoxifen. However, feelings of guilt towards her husband made her persist in having intercourse without satisfaction and therefore the patient was referred to a sexologist, who provided adequate treatment. The second case presents a man, 54 years of age, with heart failure due to a myocardial infarction, leading to loss of physical strength. He is prescribed cardiac medication that might have negative influence on his sexual response, his BMI has been increased, and his alcohol consumption has increased. In addition he had to give up his job and his sports activities. He visited his GP asking for medication to treat his erectile dysfunction. The GP suspected a predominantly somatic cause of his erectile dysfunction and started medication. The result was disappointing, even after increasing the dosage. About a year later, while consulting his cardiologist, the man addressed his sexual problem. After asking only a few questions, it became clear that he still had reasonable erections in some situations. The cardiologist explained that there was apparently still some residual erectile function and advised him to improve his lifestyle in preventing further deterioration of his erectile function. Ultimately this proved to be a good treatment option. Consideration Health care workers can address the importance of sexuality and intimate relationship in the quality of life for the chronically ill, cancer patients, and the elderly, in a basic but effective way. The Dutch Guideline Sexual Complaints provides a basis for diagnosis and management for sexual dysfunctions.
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