| 1. |
- Ai, Sizhi, et al.
(författare)
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Causal associations of short and long sleep durations with 12 cardiovascular diseases : linear and nonlinear Mendelian randomization analyses in UK Biobank
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:34, s. 3349-3357
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Tidskriftsartikel (refereegranskat)abstract
- Aims Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs. Methods and results Genetic variants associated with continuous, short (<= 6 h) and long (>= 9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P <0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P< 0.001), and suggestive evidence for atrial fibrillation (P < 0.05). However, genetically predicted long sleep duration was not associated with any CVD. Conclusion This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long steep duration is unlikely to be a causal risk factor for most CVDs. [GRAPHICS] .
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| 2. |
- Du, Yaoyao, et al.
(författare)
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Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2.
- 2011
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Ingår i: Circulation Research. - 1524-4571. ; 108, s. 79-917
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Vascular calcification is a significant contributor to cardiovascular morbidity and mortality. We recently reported that cartilage oligomeric matrix protein (COMP) is pivotal for maintaining the homeostasis of vascular smooth muscle cells (VSMCs). Whether COMP affects the process of vascular calcification is unknown. Objective: We aimed to test whether COMP modulates vascular calcification. Methods and Results: VSMC calcification in vitro was induced by calcifying media containing high inorganic phosphate or calcium. In vivo medial vessel calcification was induced in rats by 5/6 nephrectomy with a high-phosphate diet or by periadventitial application of CaCl(2) to the abdominal aorta. COMP protein level was markedly reduced in both calcified VSMCs and arteries. COMP deficiency remarkably exacerbated VSMC calcification, whereas ectopic expression of COMP greatly reduced calcification. Furthermore, COMP knockdown facilitated osteogenic markers expression by VSMCs even in the absence of calcifying media. By contrast, COMP overexpression significantly inhibited high phosphate- or high calcium-induced VSMC osteochondrogenic transition. Induction of osteogenic marker expression by COMP silencing was reversed by a soluble form of bone morphogenetic protein (BMP)-2 receptor IA, which suggests a BMP-2-dependent mechanism. Our data revealed that COMP bound directly to BMP-2 through the C terminus, inhibited BMP-2 receptor binding, and blocked BMP-2 osteogenic signaling, indicating COMP inhibits osteochondrogenic transition of VSMCs at least partially through inhibiting BMP-2. Conclusions: Our data strongly suggest that COMP is a novel inhibitor of vascular calcification. The imbalance between the effects of COMP and BMP-2 may provide new insights into the pathophysiology of vascular calcification.
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| 3. |
- Liu, Xiangdong, et al.
(författare)
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Cancer risk in patients with hepatitis C virus infection : A population-based study in Sweden
- 2017
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 6:5, s. 1135-1140
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Tidskriftsartikel (refereegranskat)abstract
- Increased risks of certain cancers have been observed in patients with hepatitis C virus (HCV) infection. However, data on other cancer sites/types are lacking. We analyzed systematically the risk of developing 35 common cancers in patients with HCV infection using a nationwide Swedish database. Patients with HCV infection were identified from the Swedish Hospital Inpatient and Outpatient Register and Primary Health Care Database, and followed until the diagnosis of cancer. Standardized incidence ratios (SIRs) were calculated for subsequent 35 common cancer sites/types between 1990 and 2010 in patients with HCV infection in Sweden. Increased risks were recorded for six cancers. The highest SIR was seen for liver cancer (36.67; 95% CI: 33.20-40.40). The decreased risk was for prostate cancer (0.73; 95% CI: 0.59-0.90) and melanoma (0.50; 95% CI: 0.30-0.79). A significant sex-difference for cancer was observed only for liver cancer (40.72; 95% CI: 36.36-45.45 for men and 27.21; 95% CI: 21.90-33.41 for women). Also, increased SIRs were noted only for liver cancer during the entire period of follow-up. HCV infection was associated with an increased incidence of liver cancer and additionally five other types of cancer. Active surveillance of other cancers may be needed in order to be diagnosed at an earlier stage.
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| 4. |
- Xue, Pei, et al.
(författare)
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No association between a common type 2 diabetes risk gene variant in the melatonin receptor gene (MTNR1B) and mortality among type 2 diabetes patients
- 2022
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Ingår i: Journal of Pineal Research. - : John Wiley & Sons. - 0742-3098 .- 1600-079X. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- The minor G risk allele in the common melatonin receptor gene (MTNR1B, rs10830963) has been associated with an increased risk of myocardial infarction among patients with type 2 diabetes (T2D). Furthermore, activating the melatonin receptor 1B through melatonin has been shown to promote cell proliferation, which could be hypothesized to increase cancer risk. Cardiovascular disease (CVD) and cancer are common causes of death among T2D patients. Using data from 14,736 T2D patients who participated in the UK Biobank investigation, we hypothesized an additive effect of the G risk allele on all-cause mortality, CVD mortality, and cancer mortality. As shown by Cox regression adjusted for confounders such as age, glucose-lowering medication, and socioeconomic status, no significant trend between the number of G risk alleles and mortality outcomes was found during the follow-up period of 11.1 years. Our negative findings do not speak against the role of this gene variant in the development of T2D, as repeatedly shown by previous large-scale studies. Instead, they may suggest that rs10830963 is less relevant for T2D patients' survival.
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| 5. |
- Xue, Pei, et al.
(författare)
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Oral Antidiabetics and Sleep Among Type 2 Diabetes Patients : Data From the UK Biobank
- 2021
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Previous small-scale studies have found that oral antidiabetic therapy is associated with sleep difficulties among patients with type 2 diabetes (T2D). Here, we used data from 11 806 T2D patients from the UK Biobank baseline investigation to examine the association of oral antidiabetic therapy with self-reported difficulty falling and staying asleep and daily sleep duration. As shown by logistic regression adjusted for, e.g., age, T2D duration, and HbA1c, patients on non-metformin therapy (N=815; 86% were treated with sulphonylureas) had a 1.24-fold higher odds ratio of reporting regular difficulty falling and staying asleep at night compared to those without antidiabetic medication use (N=5 366, P<0.05) or those on metformin monotherapy (N=5 625, P<0.05). Non-metformin patients reported about 8 to 10 minutes longer daily sleep duration than the other groups (P<0.05). We did not find significant differences in sleep outcomes between untreated and metformin patients. Our findings suggest that non-metformin therapy may result in sleep initiation and maintenance difficulties, accompanied by a small but significant sleep extension. The results of the present study must be replicated in future studies using objective measures of sleep duration and validated questionnaires for insomnia. Considering that most T2D patients utilize multiple therapies to manage their glycemic control in the long term, it may also be worth investigating possible interactions of antidiabetic drugs on sleep.
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