Reference intervals for common carotid intima-media thickness measured with echotracking: relation with risk factors.

AIMS Common carotid artery intima-media thickness (CCIMT) is widely used as a surrogate marker of atherosclerosis, given its predictive association with cardiovascular disease (CVD). The interpretation of CCIMT values has been hampered by the absence of reference values, however. We therefore aimed to establish reference intervals of CCIMT, obtained using the probably most accurate method at present (i.e. echotracking), to help interpretation of these measures. METHODS AND RESULTS We combined CCIMT data obtained by echotracking on 24 871 individuals (53% men; age range 15-101 years) from 24 research centres worldwide. Individuals without CVD, cardiovascular risk factors (CV-RFs), and BP-, lipid-, and/or glucose-lowering medication constituted a healthy sub-population (n = 4234) used to establish sex-specific equations for percentiles of CCIMT across age. With these equations, we generated CCIMT Z-scores in different reference sub-populations, thereby allowing for a standardized comparison between observed and predicted ('normal') values from individuals of the same age and sex. In the sub-population without CVD and treatment (n = 14 609), and in men and women, respectively, CCIMT Z-scores were independently associated with systolic blood pressure [standardized βs 0.19 (95% CI: 0.16-0.22) and 0.18 (0.15-0.21)], smoking [0.25 (0.19-0.31) and 0.11 (0.04-0.18)], diabetes [0.19 (0.05-0.33) and 0.19 (0.02-0.36)], total-to-HDL cholesterol ratio [0.07 (0.04-0.10) and 0.05 (0.02-0.09)], and body mass index [0.14 (0.12-0.17) and 0.07 (0.04-0.10)]. CONCLUSION We estimated age- and sex-specific percentiles of CCIMT in a healthy population and assessed the association of CV-RFs with CCIMT Z-scores, which enables comparison of IMT values for (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures obtained both in research and clinical settings.

[1]  Moyses Szklo,et al.  Risk factors for progression of common carotid atherosclerosis: the Atherosclerosis Risk in Communities Study, 1987-1998. , 2002, American journal of epidemiology.

[2]  C. Held,et al.  Prognostic implications of intima-media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris. , 2001, European heart journal.

[3]  H. Tunstall-Pedoe,et al.  Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. , 2003, European heart journal.

[4]  P Pignoli,et al.  Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. , 1986, Circulation.

[5]  H. M. den Ruijter,et al.  Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk Prediction: A Meta-Analysis , 2012 .

[6]  G. Rossi,et al.  Diagnosis and Classification of Diabetes Mellitus The information that follows is based largely on the reports of the Expert Committee on the Diagnosis and Classification of Diabetes (Diabetes Care 20:1183–1197, 1997, and Diabetes Care 26:3160–3167, 2003). , 2008, Diabetes Care.

[7]  M. Kenward,et al.  Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls , 2009, BMJ : British Medical Journal.

[8]  Qingxia Chen,et al.  Missing covariate data in medical research: to impute is better than to ignore. , 2010, Journal of clinical epidemiology.

[9]  R. Schnabel,et al.  Sex differences in early carotid atherosclerosis (from the community-based Gutenberg-Heart Study). , 2011, The American journal of cardiology.

[10]  Diederick E Grobbee,et al.  Common Carotid Intima-Media Thickness and Risk of Acute Myocardial Infarction: The Role of Lumen Diameter , 2005, Stroke.

[11]  Albert Hofman,et al.  Increased common carotid intima-media thickness. Adaptive response or a reflection of atherosclerosis? Findings from the Rotterdam Study. , 1997, Stroke.

[12]  P. Zimmet,et al.  Diagnosis and classification of diabetes mellitus , 2002 .

[13]  Arnold P G Hoeks,et al.  Assessment of spatial inhomogeneities in intima media thickness along an arterial segment using its dynamic behavior. , 2003, American journal of physiology. Heart and circulatory physiology.

[14]  Patrick Royston,et al.  A method for estimating age‐specific reference intervals (‘normal ranges’) based on fractional polynomials and exponential transformation , 1998 .

[15]  Who Consultation on Obesity Obesity: preventing and managing the global epidemic. Report of a WHO consultation. , 2000, World Health Organization technical report series.

[16]  P. Zimmet,et al.  Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO Consultation , 1998, Diabetic medicine : a journal of the British Diabetic Association.

[17]  Diederick E Grobbee,et al.  Carotid Intima-Media Thickness Measurements in Intervention Studies: Design Options, Progression Rates, and Sample Size Considerations: A Point of View , 2003, Stroke.

[18]  R. Reneman,et al.  An integrated system for the non-invasive assessment of vessel wall and hemodynamic properties of large arteries by means of ultrasound. , 1999, European journal of ultrasound : official journal of the European Federation of Societies for Ultrasound in Medicine and Biology.

[19]  A. Dominiczak,et al.  2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) , 2007, European heart journal.

[20]  Renata Cifkova,et al.  Erratum: Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension and of the European Society of Cardiology (Journal of Hypertension (2007) 25, (1105-1187)) , 2007 .

[21]  Issa J Dahabreh,et al.  Index event bias as an explanation for the paradoxes of recurrence risk research. , 2011, JAMA.

[22]  Patrick Royston,et al.  Age-specific reference intervals for normally distributed data , 1998 .

[23]  G. Berglund,et al.  Sex differences in the relationships between BMI, WHR and incidence of cardiovascular disease: a population-based cohort study , 2006, International Journal of Obesity.

[24]  D. Levy,et al.  Impact of high-normal blood pressure on the risk of cardiovascular disease. , 2002, The New England journal of medicine.

[25]  D. Mozaffarian,et al.  Measures of adiposity and future risk of ischemic stroke and coronary heart disease in older men and women. , 2011, American journal of epidemiology.

[26]  Christopher B. Kendall,et al.  Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. , 2008, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[27]  Po Box,et al.  Excess risk of fatal coronary heart disease associated with diabetes in men and women:meta-analysis of 37 prospective cohort studies , 2006 .

[28]  R S Reneman,et al.  Automated detection of local artery wall thickness based on M-line signal processing. , 1997, Ultrasound in medicine & biology.

[29]  E. Vicaut,et al.  Mannheim Carotid Intima-Media Thickness Consensus (2004–2006) , 2006, Cerebrovascular Diseases.

[30]  A. Balbarini,et al.  Carotid artery intima-media thickness: normal and percentile values in the Italian population (camp study) , 2011, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[31]  T. Laitinen,et al.  Arterial Structure and Function After Recovery From the Metabolic Syndrome: The Cardiovascular Risk in Young Finns Study , 2010, Circulation.

[32]  M. Bond,et al.  Distribution and predictors of carotid intima-media thickness in young adults. , 2007, Preventive cardiology.

[33]  D. Levy,et al.  Prediction of coronary heart disease using risk factor categories. , 1998, Circulation.

[34]  Piotr Ponikowski,et al.  2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). , 2007, European heart journal.

[35]  D. Grobbee,et al.  Body fat distribution and early arterial changes in healthy 5-year-old children , 2012, Annals of medicine.

[36]  P. Touboul,et al.  Carotid plaques, but not common carotid intima–media thickness, are independently associated with aortic stiffness , 2002, Journal of hypertension.

[37]  S. Peters,et al.  Carotid intima–media thickness: a suitable alternative for cardiovascular risk as outcome? , 2011, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[38]  The Emerging Risk Factors Collaboration Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies , 2010, The Lancet.

[39]  M A Espeland,et al.  Associations of risk factors with segment-specific intimal-medial thickness of the extracranial carotid artery. , 1999, Stroke.

[40]  Mark Woodward,et al.  Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies , 2011, The Lancet.

[41]  S. Humphries,et al.  Cross-sectional analysis of baseline data to identify the major determinants of carotid intima-media thickness in a European population: the IMPROVE study. , 2010, European heart journal.

[42]  Matthias W. Lorenz,et al.  Prediction of Clinical Cardiovascular Events With Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis , 2007, Circulation.

[43]  Gerardo Heiss,et al.  Carotid Artery Intimal‐Medial Thickness Distribution in General Populations As Evaluated by B‐Mode Ultrasound , 1993, Stroke.

[44]  M. D. de Boer,et al.  Increases in central fat mass and decreases in peripheral fat mass are associated with accelerated arterial stiffening in healthy adults: the Amsterdam Growth and Health Longitudinal Study. , 2011, The American journal of clinical nutrition.

[45]  C. Acar,et al.  Noninvasive measurement of medium-sized artery intima-media thickness in humans: in vitro validation. , 1994, Journal of vascular research.

[46]  Marcello Demi,et al.  Assessment of Carotid Stiffness and Intima‐Media Thickness From Ultrasound Data , 2010, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.