title: Association of blood lactate with carotid atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study.
abstract: OBJECTIVE
  Cardiovascular risk factors such as aging, smoking, and insulin resistance may lead to atherosclerosis through various mechanisms of which their association with mitochondrial dysfunction may be one of them. In order to examine this hypothesis, we assessed the association between elevated blood lactate, a marker of mitochondrial dysfunction, and carotid atherosclerosis.
  
  
  METHODS
  From a total of 2066 participants from the Atherosclerosis Risk In Communities Carotid MRI study, 1496 were included for this analysis. Wall Thickness and Lipid core presence were measured using gadolinium-enhanced MRI. Blood lactate was categorized into quartiles (Q1: <5.9 mg/dl, Q2: 5.9-7.2 mg/dl, Q3: 7.3-9.2 mg/dl, and Q4: >9.2 mg/dl).
  
  
  RESULTS
  Of the 1496 study participants, 763 (51%) were females, 296 (19.8%) African American, 539 (36%) obese and 308 (20.6%) had diabetes. There was a strong and graded association between lactate and wall thickness [Q1: 1.08 mm (95% CI: 1.01 mm-1.15 mm), Q2: 1.33 mm (95% CI: 1.19 mm-1.47 mm), Q3: 1.44 (95% CI: 1.34 mm-1.54 mm) and Q4: 1.62 (95% CI: 1.53 mm-1.71 mm); p for trend <0.001] after adjusting for age, gender, ethnicity, stature, body mass index (BMI), waist circumference, LDL, High sensitivity C reactive protein (HsCRP), statin use, thiazolidinedione use, hypertension, and diabetes. This association was attenuated, but still significant, after adjusting for a marker of insulin resistance, the triglyceride/HDL ratio, [Q1: 0.96 mm (95% CI: 0.82 mm-1.10 mm), Q2: 1.17 mm (95% CI: 1.08 mm-1.26 mm), Q3: 1.18 mm (95% CI: 1.07 mm-1.29 mm), Q4: 1.22 mm (95% CI: 1.13 mm-1.31 mm), p for linear trend 0.039]. There was no association of lactate with lipid core presence after adjustment for wall thickness.
  
  
  CONCLUSIONS
  Blood lactate is associated with carotid atherosclerosis. Attenuation of the association with adjustment for triglyceride/HDL ratio, a marker of insulin resistance, suggests that lactate's association with carotid atherosclerosis may be related to insulin resistance.
authors.affiliation: Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. gpalaman@jhsph.edu
authors.forename: Ghanshyam Palamaner Subash
authors.initials: GP
authors.lastname: Shantha
authors.forename: Bruce
authors.initials: B
authors.lastname: Wasserman
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Fredrick
authors.initials: F
authors.lastname: Brancati
authors.forename: A Richey
authors.initials: AR
authors.lastname: Sharrett
authors.forename: J Hunter
authors.initials: JH
authors.lastname: Young
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood / Q000453:epidemiology / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005682:Gadolinium; D006801:Humans; D007333:Insulin Resistance; D019344:Lactic Acid / Q000097:blood*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D012111:Residence Characteristics; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D014280:Triglycerides; D019344:Lactic Acid; D005682:Gadolinium