Combined effects of hemoglobin A1c and C-reactive protein on the progression of subclinical carotid atherosclerosis: the INVADE study.
OBJECTIVE
Glycohemoglobin (hemoglobin A1c [HbA1c]) and high-sensitivity C-reactive protein (hsCRP) are risk indicators for atherosclerosis. Limited information exists regarding the combined effects of inflammation and hyperglycemia. We investigated the joint effects of both parameters on early carotid atherosclerosis progression and major vascular events in diabetic and nondiabetic subjects.


METHODS
We analyzed the data of INVADE (Intervention Project on Cerebrovascular Diseases and Dementia in the Community of Ebersberg, Bavaria), a prospective, population-based study conducted in 3534 subjects (mean age, 69 years). In addition to common risk factors, measurements of carotid intima-media thickness (IMT), hsCRP, and HbA1c were performed at baseline and after 2 years of follow-up.


RESULTS
For the entire population, IMT progression was significantly related to HbA1c (P=0.003) but not to hsCRP (P=0.06) after risk factor adjustment. The interaction hsCRPxHbA1c was highly significant (P=0.001), and the most pronounced IMT progression was seen in subjects with both parameters in the fourth quartiles compared with subjects with both parameters in the first quartiles (0.028 [0.025, 0.031] versus 0.012 mm/year [0.007, 0.019]; P=0.0013). We observed a significant joint effect of HbA1c and hsCRP on IMT progression in the diabetic (n=882) as well as the nondiabetic subgroup (n=2652). Subjects with HbA1c and hsCRP in the upper 2 quartiles had an increased risk for new vascular events (adjusted hazard ratio in diabetics: 4.3 [1.8, 7.3]; P=0.001; nondiabetics: 2.9 [1.6, 4.7]; P=0.001).


CONCLUSIONS
The combination of hyperglycemia and inflammation is associated with an advanced early carotid atherosclerosis progression and an increased risk of new vascular events in diabetic as well as nondiabetic subjects.
Sander
Dirk
D
Department of Neurology, Technical University of Munich, Munich, Germany. Dirk.Sander@neuro.med.tu-muenchen.de
Schulze-Horn
Carla
C
Bickel
Horst
H
Gnahn
Hans
H
Bartels
Eva
E
Conrad
Bastian
B
D000368:Aged; D050197:Atherosclerosis; D002097:C-Reactive Protein / Q000502:physiology*; D002318:Cardiovascular Diseases; D002340:Carotid Artery Diseases / Q000097:blood* / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006442:Glycated Hemoglobin / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012306:Risk; D012307:Risk Factors; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D002097:C-Reactive Protein; D006442:Glycated Hemoglobin