Decompressive hemicraniectomy for space-occupying brain infarction: Nationwide population-based registry study

Objective: We analyzed data from the Norwegian Stroke Registry (NSR) to study access to and outcomes of decompressive hemicraniectomy for brain infarction in a nationwide routine clinical setting. We also discretionary assessed whether the outcomes were comparable with those achieved in randomized controlled trials (RCTs), and whether the use was in accordance with guidelines. Methods: The NSR is a nationwide (population 5.3 million) clinical quality registry. We included all stroke-cases operated in 2017 through 2019, and retrieved data on baseline characteristics, treatment and functional outcome after three months (dichotomized modified Rankin Scale score; favorable (0-3) or unfavorable (4-6)). Crude treatment rates and the expected proportion of patients transferred from a local hospital to a stroke-center for the operation were estimated, based on the total population’s distribution of residency. Results: The 68 cases were 17 (25%) women and 51 (75%) men with a median National Institute of Health Stroke Scale (NIHSS) score on admission of 14.0 (inter-quartile range (IQR) 11.0) and a median time from onset to hemicraniectomy of 34.3 (IQR 40.9) hours. The crude treatment rate varied between regions from 0.29 to 1.40 operations per 100,000 population per year, and the proportion transferred from a local hospital (50%) was lower than expected (68%). A favorable outcome was achieved in 20/52 (38.5%) cases. Conclusions: The findings indicate gender- and geographic-inequalities in access. Among operated cases, outcomes were comparable with those reported from RCTs, and the use in accordance with recommendations in the current guidelines from the American Stroke Association

Impact of chronic inflammation, assessed by hs-CRP, on the association between red cell distribution width and arterial cardiovascular disease: the Tromso Study

Red cell distribution width (RDW), a measure of variability in size of circulating erythrocytes, is associated with arterial cardiovascular disease (CVD), but the underlying mechanism remains unclear. We aimed to investigate the impact of chronic inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) on this relationship, and explore whether RDW could be a mediator in the causal pathway between inflammation and arterial CVD. Baseline characteristics, including RDW and hs-CRP, were obtained from 5,765 individuals attending a population-based cohort study. We followed up participants from inclusion in the fourth survey of the Tromsø Study (1994/1995) until December 31, 2012. Multivariable Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for incident myocardial infarction (MI) and ischemic stroke across quintiles of hs-CRP and RDW. Subjects with hs-CRP in the highest quintile had 44% higher risk of MI (HR: 1.44, 95% CI: 1.14–1.80), and 64% higher risk of ischemic stroke (HR: 1.64, 95% CI: 1.20–2.24) compared with subjects in the lowest quintile. RDW mediated 7.2% (95% CI: 4.0–30.8%) of the association between hs-CRP and ischemic stroke. Subjects with RDW in the highest quintile had 22% higher risk of MI (HR: 1.22, 95% CI: 0.98–1.54) and 44% higher risk of ischemic stroke (HR: 1.44, 95% CI: 1.06–1.97) compared with subjects in the lowest quintile. These risk estimates were slightly attenuated after adjustments for hs-CRP. Our findings suggest that chronic inflammation is not a primary mechanism underlying the relationship between RDW and arterial CVD

Resting heart rate predicts incident myocardial infarction, atrial fibrillation, ischaemic stroke and death in the general population: The Tromsø Study

Background: Elevated resting heart rate (RHR) increases risk of death overall, but a comprehensive picture of the associations between RHR, cardiovascular morbidity and mortality events has not yet been presented. We aimed to investigate the effect of RHR on the risk of 5 cardiovascular events: incident myocardial infarction (MI), incident atrial fibrillation (AF), incident ischaemic stroke, total death and cardiovascular death in a general population from Norway. Methods: We followed 24 489 men and women from the Tromsø Study 1994–1995, a population-based cohort study, for 18 years, and analysed the association between RHR and the investigated cardiovascular events. Sex-specific Cox regression with time-dependent covariates was applied with the best-fitting fractional polynomials of RHR. Results: Among men, an independent positive relationship was observed for MI and AF (adjusted HR for AF per 20 bpm increase=1.14; 95% CI 1.02 to 1.27). In women, the corresponding HR for MI was 1.23 (1.09 to 1.40). A J-shaped association was observed for ischaemic stroke in women when compared with a RHR of 70 bpm (HR for 50 bpm=1.31; 0.90 to 1.90; HR for 100 bpm=1.32; 1.04 to 1.69). Total and cardiovascular death showed a strong positive association with RHR in men. In women, the pattern for total death was similar. Conclusions: RHR is an independent risk factor for several cardiovascular events. A novel finding is the positive association between RHR and AF in men and the sex difference in association with ischaemic stroke

Secondary prevention care and effect: total and low-density lipoprotein cholesterol levels and lipid-lowering drug use in women and men after incident myocardial infarction - the Tromso Study 1994-2016

Background: Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported. Design: We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study. Methods: We followed 10,005 participants (54% women) attending the Tromsø Study 1994–1995 and 8483 participants (55% women) attending the Tromsø Study 2007–2008 for first-ever MI up to their participation in 2007–2008 and 2015–2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels. Results: A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994–2008 and 2007–2013, respectively. Mean change in total cholesterol was −2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was −1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was −0.33 (95% confidence interval [CI] −0.51 to −0.14) for total cholesterol and −0.21 (95% CI −0.37 to −0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15−2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II. Conclusions: Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target

The impact of risk factor trends on intracerebral hemorrhage incidence over the last two decades — The Tromsø Study

Background: Studies on the relationship between temporal trends in risk factors and incidence rates of intracerebral hemorrhage are scarce. Aims: To analyze temporal trends in risk factors and incidence rates of intracerebral hemorrhage using individual data from a population-based study. Methods: We included 28,167 participants of the Tromsø Study enrolled between 1994 and 2008. First-ever intracerebral hemorrhages were registered through 31 December 2013. Hazard ratios (HRs) for intracerebral hemorrhage were analyzed by Cox proportional hazards models, risk factor levels over time by generalized estimating equations, and incidence rate ratios (IRR) by Poisson regression. Results: We registered 219 intracerebral hemorrhages. Age, male sex, systolic blood pressure (BP), diastolic BP, and hypertension were associated with intracerebral hemorrhage. Hypertension was more strongly associated with nonlobar intracerebral hemorrhage (HR 5.08, 95% CI 2.86–9.01) than lobar intracerebral hemorrhage (HR 1.91, 95% CI 1.12–3.25). In women, incidence decreased significantly (IRR 0.46, 95% CI 0.23–0.90), driven by a decrease in non-lobar intracerebral hemorrhage. Incidence rates in men remained stable (IRR 1.27, 95% CI 0.69–2.31). BP levels were lower and decreased more steeply in women than in men. The majority with hypertension were untreated, and a high proportion of those treated did not reach treatment goals. Conclusions: We observed a significant decrease in intracerebral hemorrhage incidence in women, but not in men. A steeper BP decrease in women may have contributed to the diverging trends. The high proportion of untreated and sub-optimally treated hypertension calls for improved strategies for prevention of intracerebral hemorrhage

The DBP Phenotype Gc-1f/Gc-1f is associated with reduced risk of cancer. The Tromsø Study

Background and Objective In addition to its role as a transport protein, the vitamin D binding protein (DBP) may also affect lipid metabolism, inflammation and carcinogenesis. There are three common variants of the DBP, Gc1s (1s), Gc1f (1f), Gc2 (2) that result in six common phenotypes (1s/1s, 1s/ 1f, 1s/2, 1f/1f, 1f/2, and 2/2). These phenotypes can be identified by genotyping for the two single nucleotide polymorphisms rs7041 and rs4588 in the GC gene. The DBP variants have different binding coefficients for the vitamin D metabolites, and accordingly there may be important relations between DBP phenotypes and health. Methods DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI), type 2 diabetes (T2DM), cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2010- 2013. Genotyping was performed for rs7041 and rs4588 and serum 25-hydroxyvitamin D (25(OH)D) was measured. Results Genotyping for rs7041 and rs4588 was performed successfully in 11 704 subjects. Among these, 1660 were registered with incident MI, 958 with T2DM, 2410 with cancer and 4318 had died. Subjects with the DBP phenotype 1f/1f had 23 – 26 % reduced risk of incident cancer compared to the 1s/1s and 2/2 phenotypes (P < 0.02, Cox regression with gender as covariate). Differences in serum 25(OH)D levels could not explain the apparent cancer protective effect of the DBP variant 1f. In addition to cancer and 25(OH)D, there were significant associations between DBP phenotype and body height, hip circumference and serum calcium. Conclusion There are important biological differences between the common DBP phenotypes. If the relation between the DBP variant 1f and cancer is confirmed in other studies, determination of DBP phenotype may have clinical importance

Correction: Genetic Variations in the Vitamin D Receptor Predict Type 2 Diabetes and Myocardial Infarction in a Community-Based Population: The Tromsø Study.

[This corrects the article DOI: 10.1371/journal.pone.0145359.]