Pragmatiske studier – hva er det?

Konseptet pragmatiske studier ble foreslått av Schwartz og Lellouch i 1967 og problematiserte to viktige aspekter ved utprøving av ny behandling, nemlig forståelse og beslutning (1). Tradisjonelle forklarende effektstudier (explanatory trials) har som mål å øke vår forståelse ved å vise om en behandling virker per se, ofte under optimale forhold med nøye utvalgte studiedeltakere og utfallsmål. Pragmatiske studier skal derimot vise om en behandling virker i den kliniske hverdagen, helst på alle typer av aktuelle pasienter. Større bredde i pasientutvalget kan potensielt gjøre det vanskeligere å påvise klinisk relevante forskjeller, og studiene må av denne grunn ofte inkludere et stort antall pasienter. Den ideelle pragmatiske studien inkluderer en uselektert pasientgruppe som er aktuell for en type klinisk behandling, med endepunkter og oppfølging som i størst mulig grad foregår i den kliniske rutinen. Resultatene gir oss virkelighetsdata som kan understøtte beslutningen om å innføre en ny behandlingsform på generelt grunnlag. Pragmatiske studier er av interesse for beslutningstakere, fordi denne studieformen også tar sikte på å besvare spørsmål om kostnadseffekt av ny behandling som skal benyttes i alle deler av helsetjenesten

The predictive value of NT-proBNP and hs-TnT for risk of death in cardiac surgical patients

Background: European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is used for risk stratification before cardiac surgery, but whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) may add prognostic information to EuroSCORE II is not known. Methods: Preoperative (n = 640) and postoperative (n = 629) blood samples were available from cardiac surgical patients with 961-day follow-up (FINNAKI Heart study; cohort #1). The accuracy of a parsimonious risk model with NT-proBNP measurements was also tested in 90 patients with respiratory failure after cardiac surgery (FINNALI study; cohort #2). Results: Sixty-one patients (9.5%) died during follow-up in cohort #1. Preoperative NT-proBNP and hs-TnT concentrations correlated (rho = 0.58; p <0.001) and were higher in non-survivors compared to survivors: median 2027 (Q1-3 478-5387) vs. 373 (134-1354) ng/L [NT-proBNP] and 39 (16-191) vs. 13 (8-32) ng/L [hs-TnT]; p <0.001 for both. Preoperative NT-proBNP concentrations were associated with time to death after adjustment for EuroSCORE II (HR [lnNT-proBNP] 1.33 [95% CI 1.08-1.64]), p = 0.008 and reclassified patients on top of EuroSCORE II (net reclassification index 0.39 [95% CI 0.14-0.64], p = 0.003). Pre-and postoperative NT-proBNP concentrations were closely correlated (rho = 0.80, p <0.001) and postoperative NT-proBNP concentrations were also associated with long-term mortality after adjustment for EuroSCORE II. A parsimonious risk model that included age, creatinine clearance, chronic pulmonary disease, and NT-proBNP measurements provided comparable prognostic accuracy as EuroSCORE II in cohort #1 and #2 for risk of long-term mortality. hs-TnT measurements did not add to NT-proBNP measurements Conclusion: NT-proBNP measurements could improve and simplify risk prediction in cardiac surgical patients.Peer reviewe

Plasma linoleic acid levels and cardiovascular risk factors:results from the Norwegian ACE 1950 Study

Background A high intake of linoleic acid (LA), the major dietary polyunsaturated fatty acid (PUFA), has previously been associated with reduced cardiovascular (CV) morbidity and mortality in observational studies. However, recent secondary analyses from clinical trials of LA-rich diet suggest harmful effects of LA on CV health. Methods A total of 3706 participants, all born in 1950, were included in this cross-sectional study. We investigated associations between plasma phospholipid levels of LA and CV risk factors in a Norwegian general population, characterized by a relative low LA and high marine n-3 PUFA intake. The main statistical approach was multivariable linear regression. Results Plasma phospholipid LA levels ranged from 11.4 to 32.0 wt%, with a median level of 20.8 wt% (interquartile range 16.8–24.8 wt%). High plasma LA levels were associated with lower serum low-density lipoprotein cholesterol levels (standardized regression coefficient [Std. β-coeff.] −0.04, p = 0.02), serum triglycerides (Std. β-coeff. −0.10, p < 0.001), fasting plasma glucose (Std. β-coeff. −0.10, p < 0.001), body mass index (Std. β-coeff. −0.13, p < 0.001), systolic and diastolic blood pressure (Std. β-coeff. −0.04, p = 0.03 and Std. β-coeff. −0.02, p = 0.02, respectively) and estimated glomerular filtration rate (Std. β-coeff. −0.09, p < 0.001). We found no association between plasma LA levels and high-density lipoprotein cholesterol levels, glycated hemoglobin, carotid intima-media thickness, or C-reactive protein. Conclusion High plasma LA levels were favorably associated with several CV risk factors in this study of a Norwegian general population

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)

Lifetime obesity trends are associated with subclinical myocardial injury: The Trøndelag health study

Background Obesity is associated with subclinical myocardial injury as quantified by concentrations of cardiac troponin T, but whether lifetime excess weight history is associated with increased concentrations of cardiac troponin I (cTnI) and how indices of abdominal adiposity and glycemic dysregulation affect these associations remain unclear. Methods We analyzed cTnI with a high-sensitivity assay in 9739 participants in the Trøndelag Health (HUNT) Study at study visit 4 (2017–2019). BMI was assessed at study Visit 1 (1984–1986), 2 (1995–1997), 3 (2006–2008), and 4. Results Median age at visit 4 was 68.7 years and 59% were women. Concentrations of cTnI were detectable in 84.1% of study participants, with a median of 2.5 (1.5–4.5 ng/L). We identified three clusters of BMI trajectories from visit 1 to 4, (1) stable normal weight, (2) stable overweight, and (3) stable obesity. Participants in clusters 2 and 3 were at increased risk of elevated concentrations of cTnI at visit 4 (odds ratio 1.27, 95% CI 1.09–1.47, and odds ratio 1.70, 95% CI 1.33–2.17, p for trend <0.001). Participants in cluster 3 had 22.0 (95% CI 14.1–29.9) higher concentrations of cTnI compared to participants in cluster 1 (p for trend <0.001). Dysregulated glucose metabolism and abdominal obesity did not influence our results. Conclusions Individuals with stable overweight or obesity are at increased risk of subclinical myocardial injury, independently of glycemic dysregulation and abdominal adiposity. Our data support a direct detrimental effect of long-standing obesity on cardiovascular health

Lifetime obesity trends are associated with subclinical myocardial injury: The Trøndelag health study

Background Obesity is associated with subclinical myocardial injury as quantified by concentrations of cardiac troponin T, but whether lifetime excess weight history is associated with increased concentrations of cardiac troponin I (cTnI) and how indices of abdominal adiposity and glycemic dysregulation affect these associations remain unclear. Methods We analyzed cTnI with a high-sensitivity assay in 9739 participants in the Trøndelag Health (HUNT) Study at study visit 4 (2017–2019). BMI was assessed at study Visit 1 (1984–1986), 2 (1995–1997), 3 (2006–2008), and 4. Results Median age at visit 4 was 68.7 years and 59% were women. Concentrations of cTnI were detectable in 84.1% of study participants, with a median of 2.5 (1.5–4.5 ng/L). We identified three clusters of BMI trajectories from visit 1 to 4, (1) stable normal weight, (2) stable overweight, and (3) stable obesity. Participants in clusters 2 and 3 were at increased risk of elevated concentrations of cTnI at visit 4 (odds ratio 1.27, 95% CI 1.09–1.47, and odds ratio 1.70, 95% CI 1.33–2.17, p for trend <0.001). Participants in cluster 3 had 22.0 (95% CI 14.1–29.9) higher concentrations of cTnI compared to participants in cluster 1 (p for trend <0.001). Dysregulated glucose metabolism and abdominal obesity did not influence our results. Conclusions Individuals with stable overweight or obesity are at increased risk of subclinical myocardial injury, independently of glycemic dysregulation and abdominal adiposity. Our data support a direct detrimental effect of long-standing obesity on cardiovascular health

Relative prognostic value of cardiac troponin I and C-reactive protein in the general population (from the Nord-Trøndelag Health [HUNT] Study)

C-reactive protein and cardiac troponin I measured with high-sensitivity assays (high-sensitivity C-reactive protein [hs-CRP] and high-sensitivity troponin I [hs-TnI]) have been associated with risk of fatal and nonfatal cardiovascular events in the general population. The relative prognostic merits of hs-CRP and hs-TnI, and whether these markers of inflammation and subclinical myocardial injury provide incremental information to established cardiovascular risk prediction models, remain unclear. hs-CRP and hs-TnI were measured in 9,005 participants from the prospective observational Nord-Trøndelag Health (HUNT) study. All study subjects were free from known cardiovascular disease at baseline. During a median follow-up period of 13.9 years, 733 participants reached the composite end point of hospitalization for acute myocardial infarction or heart failure, or cardiovascular death. In adjusted models, increased hs-TnI concentrations (>10 ng/L for women and >12 ng/L for men) were associated with the incidence of the composite end point (hazard ratio 3.61, 95% confidence interval [CI] 2.89 to 4.51]), whereas the risk associated with increased hs-CRP concentrations (>3 mg/L for both genders) appeared to be weaker (HR 1.71, 95% CI 1.40 to 2.10). The addition of hs-TnI to established cardiovascular risk prediction models led to a net reclassification improvement of 0.35 (95% CI 0.27 to 0.42), superior to that of hs-CRP (0.21, 95% CI 0.13 to 0.28). The prognostic accuracy of hs-TnI, assessed by C-statistics, was significantly greater than that of hs-CRP (0.753, 95% CI 0.735 to 0.772, vs 0.644, 95% CI 0.625 to 0.663). In conclusion, in subjects from the general population without a history of cardiovascular disease, hs-TnI provides prognostic information superior to that provided by hs-CRP and may therefore be a preferred marker for targeted prevention