Pressmeddelande från Sahlgrenska akademin
2018-08-16
 
Rätt komponerad behandling och livsstilsförändringar kan avsevärt minska riskerna för hjärt-kärlsjukdom i spåren av diabetes typ 2, visar en studie publicerad i The New England Journal of Medicine. I vissa fall kan de förhöjda riskerna i det närmaste elimineras.
 
– Det här är definitivt positiva nyheter. Studien visar att patienter med typ 2-diabetes och optimal riskfaktorkontroll hade oerhört låg risk för förtida död, hjärtinfarkt och stroke, säger Aidin Rawshani, AT-läkare och doktorand vid institutionen för medicin, Sahlgrenska akademin, och försteförfattare till artikeln.
 
Studien bygger på uppgifter ur Nationella Diabetesregistret om cirka 300 000 patienter med diabetes typ 2 under perioden 1998-2014. Dessa personer har jämförts med uppemot fem gånger så många köns- och åldersmatchade kontrollpersoner ur allmänna befolkningen.
 
Full kontroll – lägre risk
Resultaten visar att det finns personer med typ 2-diabetes som inte har mer än knappt tio procents förhöjd risk för förtida död, hjärtinfarkt och stroke jämfört med folk i allmänhet. Risken för hjärtsvikt är i den här gruppen 45 procent högre än hos kontrollpersonerna.
 
I andra änden av skalan finns personer med typ 2-diabetes och hela tiofaldigt ökad risk för hjärtinfarkt, hjärtsvikt och stroke, respektive femfaldigt ökad risk för förtida död, jämfört med kontrollerna.
 
Avgörande är hur väl ett antal riskfaktorer kontrolleras, med hjälp av läkemedel och genom att personen är rökfri. Det handlar om blodtryck, långtidsblodsocker, lipidstatus (fetter och fettliknande ämnen i blodet), njurfunktion och rökning.
 
Just rökningen visade sig vara den tyngsta riskfaktorn för förtida död, medan förhöjda blodsockernivåer var den farligaste faktorn för hjärtinfarkt och stroke.
 
Viktigast för yngre
– Genom att optimera de här fem riskfaktorerna, som alla kan påverkas, kommer man en bra bit. Vi har visat att riskerna kan kraftigt reduceras, och i vissa fall kanske till och med elimineras, säger Aidin Rawshani.
– Studien visar också att risken för komplikationer, framför allt hjärtsvikt, är störst bland dem under 55 år, fortsätter han. Därför är det extra viktigt att kontrollera och behandla riskfaktorer om man är yngre med diabetes typ 2.
 
Titel: Risk Factors, Mortality and Cardiovascular Outcomes in Patients with Type 2 diabetes; 
 
Artikeln i full text som pdf utan lösenord
eller
 
Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Aidin Rawshani, M.D., Araz Rawshani, M.D., Ph.D., Stefan Franzén, Ph.D., Naveed Sattar, M.D., Ph.D., Björn Eliasson, M.D., Ph.D., Ann-Marie Svensson, Ph.D., Björn Zethelius, M.D., Ph.D., Mervete Miftaraj, M.Sc., Darren K. McGuire, M.D., M.H.Sc., Annika Rosengren, M.D., Ph.D., and Soffia Gudbjörnsdottir, M.D., Ph.D.
 
ABSTRACT

BACKGROUND
Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients with type 2 diabetes could be reduced or eliminated.
 
METHODS
In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county.
 
We assessed patients with diabetes according to age categories and according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure).
 
Cox regression was used to study the excess risk of outcomes (death, acute myocardial infarction, stroke, and hospitalization for heart failure) associated with smoking and the number of variables outside target ranges. We also examined the relationship between various risk factors and cardiovascular outcomes.
 
RESULTS
The median follow-up among all the study participants was 5.7 years, during which 175,345 deaths occurred. Among patients with type 2 diabetes, the excess risk of outcomes decreased stepwise for each risk-factor variable within the target range.
 
Among patients with diabetes who had all five variables within target ranges, the hazard ratio for death from any cause, as compared with controls, was 1.06 (95% confidence interval [CI], 1.00 to 1.12), the hazard ratio for acute myocardial infarction was 0.84 (95% CI, 0.75 to 0.93), and the hazard ratio for stroke was 0.95 (95% CI, 0.84 to 1.07).
 
The risk of hospitalization for heart failure was consistently higher among patients with diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In patients with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death.
 
CONCLUSIONS
Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population.
 
Funded by the Swedish Association of Local Authorities and Regions and others
 
From the article
Discussion
 
Our analysis of Swedish nationwide registry data from 1998 through 2012
showed that patients with type 2 diabetes and five selected risk-factor variables
within target range had, at most, marginally higher risks of death, stroke, and
myocardial infarction than the general population. The study indicates that
having all five risk-factor variables within the target ranges could theoretically
eliminate the excess risk of acute myocardial infarction. However, there was a
substantial excess risk of hospitalization for heart failure among patients who
had all the variables within target ranges. We identified a monotonic
relationship among younger age, increasing number of variables not within
target ranges, and a higher relative risk of adverse cardiovascular outcomes. The
results suggest that there may be greater potential gains from more aggressive
treatment in younger patients with diabetes.
 
The following risk factors were considered to be the strongest predictors for
cardiovascular outcomes and death: low physical activity, smoking, and glycated
hemoglobin, systolic blood-pressure, and LDL cholesterol levels outside the
target ranges. Using real-world data, we found that levels of glycated
hemoglobin, systolic blood pressure, and LDL cholesterol that were lower than
target levels were associated with lower risks of acute myocardial infarction and
stroke.
 
Randomized trials investigating the effect of multifactorial cardiovascular
risk-factor intervention in patients with type 2 diabetes are scarce, and
contemporary studies were designed to measure the cumulative incidence of
cardiovascular events among patients with various risk factors (e.g.,
hyperglycemia, hypertension, dyslipidemia, and microalbuminuria) who received
intensive therapy, as compared with those who received conventional therapy.
 
Observational studies and randomized trials have shown inconsistent evidence of
effects of glycated hemoglobin levels below contemporary guideline levels
(<7.0%) with regard to cardiovascular events and death.
 
In the present analyses, a glycated hemoglobin level outside the target range
was a strong predictor for all outcomes, especially for atherothrombotic events,
which shows the importance of dysglycemia with regard to these complications.
Low physical activity was also a strong predictor of cardiovascular outcomes and
death, but randomized trials have not shown long-lasting beneficial effects from
increased physical activity in patients with diabetes.
 
With regard to hospitalization for heart failure, the present analyses showed
that the presence of atrial fibrillation, a high body-mass index, and a glycated
hemoglobin level and renal function outside the target ranges were the strongest
predictors. These findings indicate that cardiorenal mechanisms may contribute
to the development of heart failure in patients with type 2 diabetes. A high
body-mass index was a stronger risk factor for heart failure than for other
outcomes, which may explain why the risks associated with this outcome may
continue to be higher among patients with type 2 diabetes than among controls,
since patients with diabetes are, on average, heavier than compared controls.
Our study shows, in accordance with previous studies, that lower systolic
blood pressure is associated with lower risks of cardiovascular outcomes and
death.
 
The Systolic Blood Pressure Intervention Trial (SPRINT) showed that
systolic blood-pressure targets below guideline levels in patients without diabetes
were associated with a lower risk of cardiovascular outcomes and death.
 
However, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial
examined the same systolic blood-pressure targets in patients with type 2
diabetes (<120 mm Hg vs. <140 mm Hg) and did not show a significant effect
on cardiovascular mortality.
 
Our analysis implies that systolic blood pressure
is a central factor for virtually all outcomes in patients with diabetes, and lower
levels of systolic blood pressure are associated with significantly lower risks of
acute myocardial infarction and stroke among patients with diabetes. The
assessment of systolic blood pressure and its relation to death and heart failure
is more difficult, owing to potential reverse causality. More-specific trials of
blood-pressure reduction to differential targets in patients with type 2 diabetes
may be warranted.
 
Our observational study has several strengths but also some notable
limitations. Almost all the patients with type 2 diabetes in Sweden were
included. The epidemiologic definitions of type 2 diabetes and the outcomes are
well validated. We did not consider changes in the risk-factor variables during
follow-up, and although this would have some advantages, the approach we used
minimizes the risk of reverse causation in the interpretation of the results. In
addition, we did not distinguish between patients with all or some variables
within target range without any specific intervention and patients who had been
medically treated to attain the observed risk-factor levels. We also acknowledge
that residual confounding and reverse causation are impossible to overcome
fully. Finally, given the observational nature of this work, this cannot be a
complete comparison of the effects of treating risk factors; rather, because some
patients may have had risk-factor variables in the target ranges without
treatment, the findings represent the prognostic importance of such risk factors
for persons with diabetes.
 
In conclusion, patients with type 2 diabetes who had five risk-factor variables
within target ranges appeared to have little or no excess risks of death,
myocardial infarction, and stroke as compared with the general population.
 
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