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Schubert, J., Lindahl, B., Melhus, H., Renlund, H., Leosdottir, M., Yari, A., . . . Hagström, E. (2023). Elevated low-density lipoprotein cholesterol: An inverse marker of morbidity and mortality in patients with myocardial infarction. Journal of Internal Medicine, 294(5), 616-627
Open this publication in new window or tab >>Elevated low-density lipoprotein cholesterol: An inverse marker of morbidity and mortality in patients with myocardial infarction
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2023 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 294, no 5, p. 616-627Article in journal (Refereed) Published
Abstract [en]

Background

The incidence of atherosclerotic cardiovascular disease increases with levels of low-density lipoprotein cholesterol (LDL-C). Yet, a paradox may exist where lower LDL-C levels at myocardial infarction (MI) are associated with poorer prognoses.

Objective

To assess the association between LDL-C levels at MI with risk factor burden and cause-specific outcomes.

Methods

Statin-naive patients hospitalized for a first MI and registered in SWEDEHEART were included. Data were linked to Swedish registers. Primary outcomes were all-cause mortality and nonfatal MI. Associations between LDL-C and outcomes were assessed using adjusted proportional hazards models.

Results

Among 63,168 patients (median age, 66 years), the median LDL-C level was 3.0 mmol/L (interquartile range 2.4–3.6). Patient age and comorbidities increased as LDL-C decreased. During a median follow-up of 4.5 years, 10,236 patients died, and 4973 had nonfatal MI. Patients with the highest LDL-C had a lower risk of mortality (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71–0.80). The risk of hospitalization for pneumonia, hip fracture, chronic obstructive pulmonary disease, and new cancer diagnosis was lower with higher LDL-C (HR range, 0.40–0.81). Patients with the highest LDL-C had a greater risk of recurrent MI (HR 1.16; 95% CI 1.07–1.26).

Conclusions

Patients with the highest LDL-C levels at MI had the lowest incidence of mortality and morbidity. This seems to reflect lower age at MI, less underlying morbidities, paired with the modifiability of LDL-C. However, supporting the causal association between LDL-C and ischemic heart disease, elevated LDL-C was simultaneously associated with an increased risk of nonfatal MI.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
atherosclerosis, cholesterol, myocardial infarction, lipid lowering, observational, prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-518656 (URN)10.1111/joim.13656 (DOI)000997662000001 ()37254886 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2023-12-22 Created: 2023-12-22 Last updated: 2023-12-22Bibliographically approved
Kempen, T., Hedman, A. N., Hadziosmanovic, N., Lindner, K., Melhus, H., Nielsen, E. I., . . . Gillespie, U. (2023). Risk factors for and preventability of drug‐related hospital revisits in older patients: A post‐hoc analysis of a randomized clinical trial. British Journal of Clinical Pharmacology, 89(5), 1575-1587
Open this publication in new window or tab >>Risk factors for and preventability of drug‐related hospital revisits in older patients: A post‐hoc analysis of a randomized clinical trial
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2023 (English)In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 89, no 5, p. 1575-1587Article in journal (Refereed) Published
Abstract [en]

Aim

The aims of this study were (1) to identify older patients' risk factors for drug-related readmissions and (2) to assess the preventability of older patients' drug-related revisits.

Methods

Post hoc analysis of a randomized clinical trial with patients aged >= 65 years at eight wards within four hospitals in Sweden. (1) The primary outcome was risk factors for drug-related readmission within 12 months post-discharge. A Cox proportional hazards model was made with sociodemographic and clinical baseline characteristics. (2) Four hundred trial participants were randomly selected and their revisits (admissions and emergency department visits) were assessed to identify potentially preventable drug-related revisits, related diseases and causes.

Results

(1) Among 2637 patients (median age 81 years), 582 (22%) experienced a drug-related readmission within 12 months. Sixteen risk factors (hazard ratio >1, P < 0.05) related to age, previous hospital visits, medication use, multimorbidity and cardiovascular, liver, lung and peptic ulcer disease were identified. (2) The 400 patients experienced a total of 522 hospital revisits, of which 85 (16%) were potentially preventable drug-related revisits. The two most prevalent related diseases were heart failure (n = 24, 28%) and chronic obstructive pulmonary disease (n = 13, 15%). The two most prevalent causes were inadequate treatment (n = 23, 27%) and insufficient or no follow-up (n = 22, 26%).

Conclusion

(1) Risk factors for drug-related readmissions in older hospitalized patients were age, previous hospital visits, medication use and multiple diseases. (2) Potentially preventable drug-related hospital revisits are common and might be prevented through adequate pharmacotherapy and continuity of care in older patients with cardiovascular or lung disease.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
National Category
Geriatrics
Identifiers
urn:nbn:se:uu:diva-493175 (URN)10.1111/bcp.15621 (DOI)000899733300001 ()
Funder
Region Gavleborg, CFUG‐658451Region Gavleborg, CFUG‐698771
Available from: 2023-01-12 Created: 2023-01-12 Last updated: 2023-05-08Bibliographically approved
Sulku, J., Janson, C., Melhus, H., Ställberg, B., Bröms, K., Högman, M., . . . Nielsen, E. I. (2022). Changes in critical inhaler technique errors in inhaled COPD treatment: A one-year follow-up study in Sweden. Respiratory Medicine, 197, Article ID 106849.
Open this publication in new window or tab >>Changes in critical inhaler technique errors in inhaled COPD treatment: A one-year follow-up study in Sweden
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2022 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 197, article id 106849Article in journal (Refereed) Published
Abstract [en]

Background: Critical inhaler technique errors have been associated with lower treatment efficacy in chronic obstructive pulmonary disease (COPD). We aimed to assess and follow-up critical inhaler technique errors, and to investigate their association with COPD symptoms and exacerbations.

Methods: COPD-diagnosed primary and secondary care outpatients (n = 310) demonstrated inhaler technique with inhaler devices they were currently using. Critical errors in opening, positioning and loading the inhaler device, and exhalation through dry-powder inhalers were assessed and corrected, and the assessment was repeated one year later. COPD Assessment Test, the modified Medical Research Council dyspnoea scale and history of exacerbations were collected at both visits.

Results: The proportion of patients making >1 critical inhaler technique error was lower at follow-up in the total population (46% vs 37%, p = 0.01) and among patients with unchanged device models (46% vs 35%, p = 0.02), but not among patients with a new inhaler device model (46% vs 41%, p = 0.56). Not positioning the device correctly was the most common critical error at both visits (30% and 22%). Seventy-four percent of the patients had unchanged COPD treatment from baseline to follow-up. Treatment escalation, de-escalation, and switch was observed in 14%, 11%, and 1% of the patients, respectively. No association was found between critical errors and COPD symptoms or exacerbations.

Conclusions: Assessment and correction of inhaler technique was associated with a decrease in critical inhaler technique errors. This effect was most pronounced in patients using the same device models throughout the follow-up period.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
COPD, Inhaler technique, Critical errors, COPD treatment
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine; Lung Medicine
Identifiers
urn:nbn:se:uu:diva-439956 (URN)10.1016/j.rmed.2022.106849 (DOI)000830640600001 ()35483167 (PubMedID)
Funder
Swedish Heart Lung FoundationBror Hjerpstedts stiftelseRegion DalarnaUppsala UniversityRegion Gavleborg
Available from: 2021-04-12 Created: 2021-04-12 Last updated: 2023-01-03Bibliographically approved
Lind, T., Melo, F. R., Gustafson, A.-M., Sundqvist, A., Zhao, X. O., Moustakas, A., . . . Pejler, G. (2022). Mast cell chymase has a negative impact on human osteoblasts. Matrix Biology, 112, 1-19
Open this publication in new window or tab >>Mast cell chymase has a negative impact on human osteoblasts
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2022 (English)In: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 112, p. 1-19Article in journal (Refereed) Published
Abstract [en]

Mast cells have been linked to osteoporosis and bone fractures, and in a previous study we found that mice lacking a major mast cell protease, chymase, develop increased diaphyseal bone mass. These findings introduce the possibility that mast cell chymase can regulate bone formation, but the underlying mechanism(s) has not previously been investigated. Here we hypothesized that chymase might exert such effects through a direct negative impact on osteoblasts, i.e., the main bone-building cells. Indeed, we show that chymase has a distinct impact on human primary osteoblasts. Firstly, chymase was shown to have pronounced effects on the morphological features of osteoblasts, including extensive cell contraction and actin reorganization. Chymase also caused a profound reduction in the output of collagen from the osteoblasts, and was shown to degrade osteoblast-secreted fibronectin and to activate pro-matrix metallopeptidase-2 released by the osteoblasts. Further, chymase was shown to have a preferential impact on the gene expression, protein output and phosphorylation status of TGF beta-associated signaling molecules. A transcriptomic analysis was conducted and revealed a significant effect of chymase on several genes of importance for bone metabolism, including a reduction in the expression of osteoprotegerin, which was confirmed at the protein level. Finally, we show that chymase interacts with human osteoblasts and is taken up by the cells. Altogether, the present findings provide a functional link between mast cell chymase and osteoblast function, and can form the basis for a further evaluation of chymase as a potential target for intervention in metabolic bone diseases.

Place, publisher, year, edition, pages
Elsevier, 2022
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-484746 (URN)10.1016/j.matbio.2022.07.005 (DOI)000848284800002 ()35908613 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Heart Lung FoundationKnut and Alice Wallenberg Foundation
Available from: 2022-09-16 Created: 2022-09-16 Last updated: 2022-09-16Bibliographically approved
Michaelsson, M., Yuan, S., Melhus, H., Baron, J. A., Byberg, L., Larsson, S. C. & Michaëlsson, K. (2022). The impact and causal directions for the associations between diagnosis of ADHD, socioeconomic status, and intelligence by use of a bi-directional two-sample Mendelian randomization design. BMC Medicine, 20(1), Article ID 106.
Open this publication in new window or tab >>The impact and causal directions for the associations between diagnosis of ADHD, socioeconomic status, and intelligence by use of a bi-directional two-sample Mendelian randomization design
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2022 (English)In: BMC Medicine, E-ISSN 1741-7015, Vol. 20, no 1, article id 106Article in journal (Refereed) Published
Abstract [en]

Background Previous studies have reported associations between attention-deficit/hyperactivity disorder (ADHD) and lower socioeconomic status and intelligence. We aimed to evaluate the causal directions and strengths for these associations by use of a bi-directional two-sample Mendelian randomization (MR) design. Methods We used summary-level data from the largest available genome-wide association studies (GWAS) to identify genetic instruments for ADHD, intelligence, and markers of socioeconomic status including the Townsend deprivation index, household income, and educational attainment. Effect estimates from individual genetic variants were combined using inverse-variance weighted regression. Results A genetically predicted one standard deviation (SD) increment in the Townsend deprivation index conferred an odds ratio (OR) of 5.29 (95% confidence interval (CI) 1.89-14.76) for an ADHD diagnosis (p<0.001). A genetically predicted one SD higher education level conferred an OR of 0.30 (95% CI 0.25-0.37) (p<0.001), and a genetically predicted one SD higher family income provided an OR of 0.35 (95% CI 0.25-0.49; p<0.001). The associations remained after adjustment for intelligence whereas the lower odds of an ADHD diagnosis with higher intelligence did not persist after adjustment for liability to greater educational attainment (adjusted OR 1.03, 95% CI 0.68-1.56; p=0.87). The MR analysis of the effect of ADHD on socioeconomic markers found that genetic liability to ADHD was statistically associated with each of them (p<0.001) but not intelligence. However, the average change in the socioeconomic markers per doubling of the prevalence of ADHD corresponded only to 0.05-0.06 SD changes. Conclusions Our results indicate that an ADHD diagnosis may be a direct and strong intelligence-independent consequence of socioeconomic related factors, whereas ADHD appears to lead only to modestly lowered socioeconomic status. Low intelligence seems not to be a major independent cause or consequence of ADHD.

Place, publisher, year, edition, pages
BioMed Central (BMC)BMC, 2022
Keywords
Attention-deficit, hyperactivity disorder, ADHD, Socioeconomic status, Education, Intelligence, Income, Townsend deprivation index, Mendelian randomization, Gene, GWAS
National Category
Psychiatry Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-473190 (URN)10.1186/s12916-022-02314-3 (DOI)000779948300001 ()35399077 (PubMedID)
Funder
Swedish Research Council, 2017-00644Swedish Research Council, 2017-06100Swedish Research Council, 2019-01291
Available from: 2022-04-27 Created: 2022-04-27 Last updated: 2024-01-15Bibliographically approved
Sulku, J., Bröms, K., Högman, M., Janson, C., Lisspers, K., Malinovschi, A., . . . Nielsen, E. I. (2021). Critical inhaler technique errors in Swedish patients with COPD: a cross-sectional study analysing video-recorded demonstrations. npj Primary Care Respiratory Medicine, 31(1), Article ID 5.
Open this publication in new window or tab >>Critical inhaler technique errors in Swedish patients with COPD: a cross-sectional study analysing video-recorded demonstrations
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2021 (English)In: npj Primary Care Respiratory Medicine, E-ISSN 2055-1010, Vol. 31, no 1, article id 5Article in journal (Refereed) Published
Abstract [en]

A correct use of inhaler devices is essential in chronic obstructive pulmonary disease (COPD) treatment. Critical errors were studied by analysing 659 video-recorded demonstrations of inhaler technique from 364 COPD patients using six different inhaler device models. The majority of the included patients used two (55%) or more (20%) device models. Overall, 66% of the patients made ≥1 critical error with at least one device model. The corresponding numbers for patients using 1, 2 and ≥3 device models were 43%, 70% and 86%, respectively. The only factor associated with making ≥1 critical error was simultaneous use of two (adjusted odds ratios (aOR) 3.17, 95% confidence interval (95% CI) 1.81, 5.64) or three or more (aOR 8.97, 95% CI 3.93, 22.1) device models. In conclusion, the proportion of patients making critical errors in inhaler technique was substantial, particularly in those using several different device models. To obtain optimal COPD treatment, it is important to assess a patient's inhaler technique and to minimise the number of inhaler device models.

Place, publisher, year, edition, pages
Springer Nature, 2021
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine; Physiology
Identifiers
urn:nbn:se:uu:diva-435891 (URN)10.1038/s41533-021-00218-y (DOI)000616754300001 ()33563979 (PubMedID)
Available from: 2021-03-01 Created: 2021-03-01 Last updated: 2024-01-15Bibliographically approved
Kempen, T., Bertilsson, M., Hadziosmanovic, N., Lindner, K.-J., Melhus, H., Nielsen, E. I., . . . Gillespie, U. (2021). Effects of Hospital-Based Comprehensive Medication Reviews Including Postdischarge Follow-up on Older Patients' Use of Health Care: A Cluster Randomized Clinical Trial. JAMA Network Open, 4(4), Article ID e216303.
Open this publication in new window or tab >>Effects of Hospital-Based Comprehensive Medication Reviews Including Postdischarge Follow-up on Older Patients' Use of Health Care: A Cluster Randomized Clinical Trial
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2021 (English)In: JAMA Network Open, E-ISSN 2574-3805, Vol. 4, no 4, p. 67article id e216303Article in journal (Refereed) Published
Abstract [en]

Importance: Suboptimal use of medications is a leading cause of health care–related harm. Medication reviews improve medication use, but evidence of the possible benefit of inpatient medication review for hard clinical outcomes after discharge is scarce.

Objective: To study the effects of hospital-based comprehensive medication reviews (CMRs), including postdischarge follow-up of older patients’ use of health care resources, compared with only hospital-based reviews and usual care.

Design, Setting, and Participants: The Medication Reviews Bridging Healthcare trial is a cluster randomized crossover trial that was conducted in 8 wards with multiprofessional teams at 4 hospitals in Sweden from February 6, 2017, to October 19, 2018, with 12 months of follow-up completed December 6, 2019. The study was prespecified in the trial protocol. Outcome assessors were blinded to treatment allocation. In total, 2644 patients aged 65 years or older who had been admitted to 1 of the study wards for at least 1 day were included. Data from the modified intention-to-treat population were analyzed from December 10, 2019, to September 9, 2020.

Interventions: Each ward participated in the trial for 6 consecutive 8-week periods. The wards were randomized to provide 1 of 3 treatments during each period: CMR, CMR plus postdischarge follow-up, and usual care without a clinical pharmacist.

Main Outcomes and Measures: The primary outcome measure was the incidence of unplanned hospital visits (admissions plus emergency department visits) within 12 months. Secondary outcomes included medication-related admissions, visits with primary care clinicians, time to first unplanned hospital visit, mortality, and costs of hospital-based care.

Results: Of the 2644 participants, 7 withdrew after inclusion, leaving 2637 for analysis (1357 female [51.5%]; median age, 81 [interquartile range, 74-87] years; median number of medications, 9 [interquartile range, 5-13]). In the modified intention-to-treat analysis, 922 patients received CMR, 823 received CMR plus postdischarge follow-up, and 892 received usual care. The crude incidence rate of unplanned hospital visits was 1.77 per patient-year in the total study population. The primary outcome did not differ between the intervention groups and usual care (adjusted rate ratio, 1.04 [95% CI, 0.89-1.22] for CMR and 1.15 [95% CI, 0.98-1.34] for CMR plus postdischarge follow-up). However, CMR plus postdischarge follow-up was associated with an increased incidence of emergency department visits within 12 months (adjusted rate ratio, 1.29; 95% CI, 1.05-1.59) compared with usual care. There were no differences between treatment groups regarding other secondary outcomes.

Conclusions and Relevance: In this study of older hospitalized patients, CMR plus postdischarge follow-up did not decrease the incidence of unplanned hospital visits. The findings do not support the performance of hospital-based CMRs as conducted in this trial. Alternative forms of medication reviews that aim to improve older patients’ health outcomes should be considered and subjected to randomized clinical trials.

Place, publisher, year, edition, pages
American Medical Association (AMA)AMER MEDICAL ASSOC, 2021. p. 67
National Category
Social and Clinical Pharmacy
Research subject
Geriatrics; Pharmacokinetics and Drug Therapy; Internal Medicine; Health Care Research
Identifiers
urn:nbn:se:uu:diva-429007 (URN)10.1001/jamanetworkopen.2021.6303 (DOI)000646051200002 ()33929523 (PubMedID)
Funder
Thuréus stiftelse för främjande av geriatrisk forskningSwedish Heart Lung Foundation, FA 2017:38Swedish Heart Lung Foundation, FA2018:43
Note

Title in dissertation list of papers: Effects of hospital-based comprehensive medication reviews including post-discharge follow-ups on older patients’ healthcare utilisation (MedBridge trial): a pragmatic cluster-randomised crossover trial

Available from: 2021-01-15 Created: 2021-01-15 Last updated: 2024-01-15Bibliographically approved
Mitchell, A., Larsson, S. C., Fall, T., Melhus, H., Michaëlsson, K. & Byberg, L. (2021). Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study. Diabetologia, 64(6), 1348-1357
Open this publication in new window or tab >>Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study
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2021 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 64, no 6, p. 1348-1357Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis: Observational studies indicate that type 2 diabetes mellitus and fasting glucose levels are associated with a greater risk for hip fracture, lower bone area and higher bone mineral density (BMD). However, these findings may be biased by residual confounding and reverse causation. Mendelian randomisation (MR) utilises genetic variants as instruments for exposures in an attempt to deal with these biases. Thereby, we implemented MR to determine whether fasting glucose levels in individuals without diabetes are causally associated with bone area and BMD at the total hip.

Methods: We selected 35 single nucleotide polymorphisms strongly associated with fasting glucose (p <5×10−8) in a non-diabetic European-descent population from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n=133,010). MR was used to assess the associations of genetically predicted fasting glucose concentrations with total hip bone area and BMD in 4966 men and women without diabetes from the Swedish Mammography Cohort, Prospective Investigation of Vasculature in Uppsala Seniors, and Uppsala Longitudinal study of Adult men.

Results: In meta-analysis of the three cohorts, genetically predicted 1 mmol/L increment of fasting glucose was associated with a 2% lower total hip bone area (-0.67 cm2 [95% CI -1.30, -0.03; p=0.039]) yet tended to be associated with a 4% higher total hip BMD (0.040 g/cm2 [95% CI -0.00, 0.07; p=0.060]).

Conclusions/interpretation: Fasting glucose may be a causal risk factor for lower bone area at the hip, yet possibly for greater BMD. Further MR studies with larger sample sizes are required to corroborate these findings.

Place, publisher, year, edition, pages
Springer NatureSpringer Nature, 2021
Keywords
Mendelian randomisation, Single nucleotide polymorphisms, Fasting glucose, Bone area, Bone mineral density
National Category
Orthopaedics Endocrinology and Diabetes
Research subject
Epidemiology
Identifiers
urn:nbn:se:uu:diva-423104 (URN)10.1007/s00125-021-05410-w (DOI)000623899400001 ()33650017 (PubMedID)
Funder
SIMPLER, 2017-00644
Available from: 2020-10-19 Created: 2020-10-19 Last updated: 2024-01-15Bibliographically approved
Mitchell, A., Fall, T., Melhus, H., Wolk, A., Michaëlsson, K. & Byberg, L. (2021). Is the Effect of Mediterranean Diet on Hip Fracture Mediated Through Type 2 Diabetes and Body Mass Index?. International Journal of Epidemiology, 50(1), 234-244
Open this publication in new window or tab >>Is the Effect of Mediterranean Diet on Hip Fracture Mediated Through Type 2 Diabetes and Body Mass Index?
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2021 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 50, no 1, p. 234-244Article in journal (Refereed) Published
Abstract [en]

Background: We examined whether the inverse association between adherence to a Mediterranean diet and hip fracture risk is mediated by incident type 2 diabetes mellitus (T2DM) and body mass index (BMI).

Methods: We included 50,755 men and women from the Cohort of Swedish Men and Swedish Mammography Cohort who answered lifestyle and medical questionnaires in 1997 and 2008 (used for calculation of the Mediterranean diet score [mMED; low, medium, high] and BMI in 1997, and incident T2DM in 1997-2008). The cumulative incidence of hip fracture from the National Patient Register (2009-2014) was considered as outcome.

Results: We present conditional odds ratios (OR) [95% confidence interval, CI] of hip fracture for medium and high adherence to mMED, compared to low adherence. The total effect ORs were 0.82 [0.71, 0.95] and 0.75 [0.62, 0.91], respectively. The controlled direct effect of mMED on hip fracture (not mediated by T2DM, considering BMI as an exposure-induced confounder), calculated using inverse-probability weighting of marginal structural models, rendered ORs of 0.82 [0.72, 0.95] and 0.73 [0.60, 0.88], respectively. The natural direct effect ORs (not mediated by BMI or T2DM, calculated using flexible mediation analysis) were 0.82 [0.71, 0.95] and 0.74 [0.61, 0.89], respectively. The path-specific indirect and partial indirect natural effects ORs (through BMI or T2DM) were close to 1.

Conclusions: Mediterranean diet has a direct effect on hip fracture risk via pathways other than through T2DM and BMI. We cannot exclude mediating effects of T2DM or BMI, or that their effects cancel each other out.

Place, publisher, year, edition, pages
Oxford University Press, 2021
Keywords
Causality, Mediterranean diet, Hip fractures, Type 2 diabetes mellitus, Body mass index
National Category
Endocrinology and Diabetes Orthopaedics
Research subject
Epidemiology
Identifiers
urn:nbn:se:uu:diva-423103 (URN)10.1093/ije/dyaa239 (DOI)000637284400031 ()33367703 (PubMedID)
Funder
Swedish Research Council, 2015-05997Swedish Research Council, 2015-03527SIMPLER, 2017-00644Swedish Research Council, 2017-00644
Available from: 2020-10-19 Created: 2020-10-19 Last updated: 2024-01-15Bibliographically approved
Schubert, J., Lindahl, B., Melhus, H., Renlund, H., Leosdottir, M., Yari, A., . . . Hagström, E. (2021). Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study. European Heart Journal, 42(3), 243-252
Open this publication in new window or tab >>Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study
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2021 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 42, no 3, p. 243-252Article in journal (Refereed) Published
Abstract [en]

AIMS: Clinical trials have demonstrated that a reduction in low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular (CV) events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes and statin intensity with prognosis after a myocardial infarction (MI).

METHODS AND RESULTS: Patients admitted with MI were followed for mortality and major CV events. Changes in LDL-C between the MI and a 6- to 10-week follow-up visit were analysed. The associations between quartiles of LDL-C change and statin intensity with outcomes were assessed using adjusted Cox regression analyses. A total of 40 607 patients were followed for a median of 3.78 years. The median change in LDL-C was a 1.20 mmol/L reduction. Patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70-0.84); all-cause mortality 0.71 (0.63-0.80); CV mortality 0.68 (0.57-0.81); MI 0.81 (0.73-0.91); ischaemic stroke 0.76 (0.62-0.93); heart failure hospitalization 0.73 (0.63-0.85), and coronary artery revascularization 0.86 (0.79-0.94). Patients with ≥50% LDL-C reduction using high-intensity statins at discharge had a lower incidence of all outcomes compared with those using a lower intensity statin.

CONCLUSIONS: Larger early LDL-C reduction and more intensive statin therapy after MI were associated with a reduced hazard of all CV outcomes and all-cause mortality. This supports clinical trial data suggesting that earlier lowering of LDL-C after an MI confers the greatest benefit.

Place, publisher, year, edition, pages
Oxford University Press, 2021
Keywords
Cardiovascular mortality, Cardiovascular outcomes, LDL-C, Myocardial infarction, Secondary prevention, Statin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-430124 (URN)10.1093/eurheartj/ehaa1011 (DOI)000613897300010 ()33367526 (PubMedID)
Available from: 2021-01-07 Created: 2021-01-07 Last updated: 2024-01-15Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-6857-5973

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