| 1. |
- Patel, Riyaz S., et al.
(författare)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 2. |
- Patel, Riyaz S., et al.
(författare)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 3. |
- Vishram, Julie K.K., et al.
(författare)
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Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage : a LIFE substudy
- 2015
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 33:12, s. 2422-2430
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Tidskriftsartikel (refereegranskat)abstract
- Background: Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH).Methods: In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6-24months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP=630 events).Results: In multiple regression models adjusted for mean BP6-24months and treatment allocation, neither high BP6-24months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow-Lyon voltage and DBP6-24months SD and range (both b=0.04, P<0.01). Independently of mean BP6-24months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6-24months SD [hazard ratio per 1mmHg increase1.04, 95% confidence interval (95% CI) 1.01-1.06, P=0.005], range (hazard ratio 1.02, 95% CI 1.01-1.03, P=0.004), SBP6-24months SD (hazard ratio 1.01, 95% CI 0.99-1.02, P=0.07) and range (hazard ratio 1.006, 95% CI 1.001-1.01, P=0.04). Adjusted for the same factors, stroke was associated with DBP6-24months SD (hazard ratio 1.06, 95% CI 1.02-1.10, P=0.001), range (hazard ratio 1.03, 95% CI 1.01-1.04, P=0.001), SBP6-24months SD (hazard ratio 1.02, 95% CI 1.002-1.04, P=0.04) and range (hazard ratio 1.008, 95% CI 1.001-1.02, P=0.05), but MI was not.Conclusion: In LIFE patients, higher in-treatment BP6-24months variability was independently of mean BP6-24months associated with later CEP and stroke, but not with MI or TOD after 24 months.
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| 6. |
- Kohler, Stefan, et al.
(författare)
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Postpartum quality of life in Indian women after vaginal birth and cesarean section : a pilot study using the EQ-5D-5L descriptive system
- 2018
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Ingår i: BMC Pregnancy and Childbirth. - : BioMed Central. - 1471-2393 .- 1471-2393. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: There has been little evaluation of the postpartum quality of life (QOL) of women in India and its association with the mode of birth. This study piloted the use of the generic EQ-5D-5L questionnaire to assess postpartum QOL experienced by rural Indian women.Methods: A convenience sample of rural women who gave birth in a health facility in Gujarat or Madhya Pradesh was recruited into this pilot study. QOL was measured during three interviews within 30days of birth using the EQ-5D-5L questionnaire. Patient-level quality-adjusted life days (QALDs) were estimated. Multivariate regression was used to adjust for selected baseline characteristics.Results: Forty-six women with cesarean section and 178 with vaginal birth from 17 public and private health facilities were studied. Postpartum QOL in both groups improved between interviews 1 and 3. Comparing between vaginal and cesarean births indicated that the vaginal birth group had a higher QOL (0-3 days postpartum: 0.28 vs. 0.57, 3-7 days postpartum: 0.59 vs. 0.81; P<0.001) and was more likely to report no or slight problems in 4 of 5 health dimensions (mobility, self-care, usual activities, painordiscomfort; P0.04) during interviews 1 and 2. Postpartum QOL converged, but still differed between groups by the time of interview 3 (21-30 days postpartum: 0.85 vs. 0.93; P<0.001). While most women reported no problems by the end of the first postpartum month, the difference in the ability to perform usual activities persisted (P=0.001). In result, fewer QALDs were attained by women in the cesarean section group between day 1 and day 21 postpartum (13.1 vs. 16.6 QALDs; P<0.001). Subgroup analysis showed that having had an episiotomy during vaginal birth was also associated with reduced QOL postpartum, but to a lesser extent than cesarean section. Similar results were obtained when adjusting for socioeconomic, pregnancy and birth characteristics, but postpartum QOL already ceased to be statistically different between groups before interview 3.Conclusions: Vaginal births, even with episiotomy, were associated with a higher postpartum QOL than cesarean births among the Indian women in our pilot study. Finding these expected results suggests that the EQ-5D-5L questionnaire is asuitable instrumentto assess postpartum QOL in Indian women.
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| 8. |
- Lindholm, Daniel, 1982-, et al.
(författare)
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Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 70:7, s. 813-826
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Tidskriftsartikel (refereegranskat)abstract
- Background Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD).Objectives This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD.Methods In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study.Results During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This “ABC-CHD” model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts.Conclusions This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903)
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| 9. |
- Sjöström, Olle, 1973-
(författare)
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Risk and survival for colorectal cancer in northern Sweden : sociodemographic factors and surveillance programs
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundColorectal cancer (CRC) – i.e., cancer in the colon or rectum – is one of the most common cancers both globally and in Sweden. The risk for CRC is mainly related to age, heredity, and life-style risk factors. Previous studies have also demonstrated that individuals with lower socioeconomic status (SES), living alone, or far from care facilities may have a higher risk for CRC or a worse outcome. In contrast to life-style or sociodemographic-associated risks, an inherited risk for CRC is difficult to modify. However, colonoscopic surveillance programs can be help prevent CRC in families with a known hereditary risk.The Northern Health Care Region (northern Sweden) is the most sparsely populated region in Sweden, and travel distances to care can be long. The population in Northern Sweden is on average older and has lower SES compared with the rest of the country. The impact of these sociodemographic differences on CRC in northern Sweden is not well known. AimThis thesis analyses CRC in a northern Sweden setting with regards to incidence, survival, and associated sociodemographic risk factors, including prevention for individuals with increased hereditary risk.MethodsPapers I and II, cohort studies from the Risk North database, link individual data from health care registers to other sociodemographic registers. In Paper I, the incidence, mortality, and survival for all CRC cases in northern Sweden were compared with the rest of Sweden for the period 2007-2013. Uni- and multivariable Cox regression analysis were used to assess the impact of sociodemographic factors and tumour stage on survival by calculating hazard ratios (HR). In Paper II, we analysed any association between travel time to care and CRC survival in northern Sweden during 2007-2013 using the same type of Cox regression analysis. Papers III and IV are based on a cohort of individuals with a family history of CRC, prospectively recorded from 1995 to 2012 in the colonoscopic surveillance register at the Cancer Prevention Clinic at Umeå University Hospital. In Paper III, we evaluated the cancer preventive effect of the performed colonoscopic surveillance. Observed cases of CRC were compared to a cohort estimate of cases without surveillance. Compliance with surveillance and colonoscopic quality was also analysed. In Paper IV, we examined the cost-effectiveness of the colonoscopic surveillance program in Paper III. A cost-utility analysis with a societal perspective was used and the stability of the results was tested in a sensitivity analysis. ResultsThe age-adjusted incidence in colon cancer was 12.7% lower in northern compared to southern Sweden or 35.9/100 000 vs. 41.1/100 000 person years (p < 0.01). For rectal cancer, the incidence was 10.5% lower in the north (17.6 vs. 19.7 p <0.01). In subgroup analysis, the largest difference in incidence between northern and southern Sweden was found among individuals > 79 years age (colon - 190 vs. 237 ≈ 19.6%, rectal 72.4 vs. 88.0 ≈ 17.7%). For all of Sweden, the incidence in colorectal cancer was higher in males, individuals with lower SES, or individuals living alone. In univariable analyses of survival (all-cause and cause-specific) for colon and rectal cancer patients in all of Sweden, patients with high SES or co-habiting had a significantly better outcome compared to patients with low SES or living alone. HR for death ranged from 0.60 to 0.85 in the better-favoured risk group. No differences in colon or rectal cancer survival between northern and southern Sweden were demonstrated in the univariable analysis. However, in multivariable survival analysis, all-cause survival for colon cancer patients was better in southern Sweden (HR 0.92; 95% CI 0.86 – 0.97). For cause-specific survival for colon cancer or in any analysis for rectal cancer, no differences between northern and southern Sweden were demonstrated. In analysis of travel time, no association between travel time and survival was found. In the evaluation of the colonoscopic surveillance programme, one case of CRC was observed, compared to 9.5-10.5 expected cases. Standardised Incidence Ratio (SIR) between observed and expected cases of CRC was 0.10 (CI 95% 0.0012–0.53) to 0.11 (CI 95% 0.0014–0.59. The compliance to the surveillance program was 90%. The adenoma detection rate was 14%, and 10% of the examinations were incomplete. In the cost-utility analysis, the net cost for surveillance was 233 038 €, while saving 64.8 Quality Adjusted Life Years (QALYs) compared to non-surveillance. The resulting Incremental Cost-Effectiveness Ratio (ICER) was 3596 €/QALY, ranging from -4620 €/QALY in the best-case scenario to 33 779 € /QALY in the worst-case scenario.ConclusionThe incidence of CRC was lower in northern Sweden and most evident in the elderly, raising questions on differences in life-style between northern and southern Sweden in the past. There were considerable sociodemographic disparities in CRC survival in Sweden, including a lower all-cause survival for colon cancer patients in the north. In this study, travel time to care in northern Sweden did not affect survival and the lower all-cause survival in northern Sweden cannot be fully explained. The colonoscopic surveillance of families in northern Sweden with inherited risk for CRC had a good cancer preventive effect, including a high cost-effectiveness. The reasons for the good effect may be high compliance, since the quality of the colonoscopies was moderate.
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| 10. |
- Xu, H., et al.
(författare)
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Lipophilic index, kidney function, and kidney function decline
- 2016
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 31, s. 177-177
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. Methods and results: Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended reexamination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction >= 30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m(2) 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m(2), p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). Conclusions: A high LI was associated with lower kidney function, kidney function decline, and CKD progression.
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