Varying Definitions of Carotid Intima-Media Thickness and Future Cardiovascular Disease: A Systematic Review and Meta-Analysis

Abstract

Background: Carotid intima-media thickness (cIMT) has been widely used as a predictor of future cardiovascular disease (CVD); however, various definitions of cIMT exist. This study provides a systematic review and meta-analysis of the associations between different cIMT definitions and CVD.

Methods and results: A systematic review of the different cIMT definitions used in prospective cohort studies was performed. The relationships between cIMT of different definitions (common carotid artery IMT [CCA-IMT], internal carotid artery IMT [ICA-IMT], combined segments [combined-IMT], mean CCA-IMT, and maximum CCA-IMT) with future stroke, myocardial infarction (MI), and CVD events were analyzed using random effects models. Among 2287 articles, 18 articles (14 studies) with >10 different cIMT definitions were identified and included in our meta-analysis. After adjusting for age and sex, a 1-SD increase in CCA-IMT was associated with future stroke (hazard ratio [HR], 1.32 [95% CI, 1.27-1.38]), MI (HR, 1.27 [95% CI, 1.22-1.33]), and CVD events (HR, 1.28 [95% CI, 1.19-1.37]). A 1-SD increase in ICA-IMT was related to future stroke (HR, 1.25 [95% CI, 1.11-1.42]) and CVD events (HR, 1.25 [95% CI, 1.04-1.50]) but not MI (HR, 1.26 [95% CI, 0.98-1.61]). A 1-SD increase in combined-IMT was associated with future stroke (HR, 1.30 [95% CI, 1.08-1.57]) and CVD events (HR, 1.36 [95% CI, 1.23-1.49]). Maximum CCA-IMT was more strongly related than mean CCA-IMT with risk of MI, and both measures were similarly associated with stroke and CVD events.

Conclusions: Combined-IMT is more strongly associated with CVD events compared with single-segment cIMT definitions. Maximum CCA-IMT shows a stronger association with MI than mean CCA-IMT. Further research is warranted to validate our findings and to standardize the cIMT measurement protocol, as well as to explore underlying mechanisms.

Keywords: atherosclerosis; cardiovascular disease risk; carotid intima‐media thickness; meta‐analysis; segment/definition.

Figure 1. Flow diagram of study screening.

Figure 2. A schematic of the different definitions and segment lengths of carotid intima‐media thickness (cIMT) of the studies included in the systematic review.

A total of 13 studies provided details on cIMT definition. Anatomic marks used as reference points were the tip of the flow divider (A); the beginning of the dilation of bulb (B). All studies measured far walls except those with *, where it was measured on far and near walls. Further details can be found in Data S2. ARIC indicates Atherosclerosis Risk in Communities; Bif, carotid bifurcation; BLSA, Beijing Longitudinal Study of Aging; CAPS, Carotid Atherosclerosis Progression Study; CCA, common carotid artery; CHS, Cardiovascular Health Study; CVDFACTS, Cardiovascular Diseases Risk Factor Two‐Township Study; HNR, Heinz Nixdorf Recall; ICA, internal carotid artery; LitHiR, Lithuanian High Cardiovascular Risk; MDCS, Malmö Diet and Cancer Study; PRC‐USA, People's Republic of China‐United States of America; and SMART, Second Manifestations of Arterial Disease.

Figure 3. Meta‐analysis of common carotid artery intima‐media thickness (CCA‐IMT) and cardiovascular disease (CVD).

Forest plots of hazard ratios per 1‐SD increment in CCA‐IMT, adjusted for age and sex. (A) Hazard ratio for stroke. (B) Hazard ratio for myocardial infarction. (C) Hazard ratio for CVD events. ARIC indicates Atherosclerosis Risk in Communities; BLSA, Beijing Longitudinal Study of Aging; CAPS, Carotid Atherosclerosis Progression Study; CCCC, Chin‐Shan Community Cardiovascular Cohort Study; CHS, Cardiovascular Health Study; CVDFACTS, Cardiovascular Diseases Risk Factor Two‐Township Study; HNR, Heinz Nixdorf Recall; HR, hazard ratio; LitHiR, Lithuanian High Cardiovascular Risk; MDCS, Malmö Diet and Cancer Study; MI, myocardial infarction; and SMART, Second Manifestations of Arterial Disease.

Figure 4. Meta‐analysis of internal carotid artery intima‐media thickness (ICA‐IMT) and cardiovascular disease (CVD).

Forest plots of hazard ratios per 1‐SD increment in ICA‐IMT, adjusted for age and sex. (A) Hazard ratio for stroke. (B) Hazard ratio for myocardial infarction. (C) Hazard ratio for CVD events. CAPS indicates Carotid Atherosclerosis Progression Study; CHS, Cardiovascular Health Study; and HR, hazard ratio.

Figure 5. Meta‐analysis of combined intima‐media thickness (combined‐IMT) and cardiovascular disease (CVD).

Forest plots of hazard ratios per 1‐SD increment in combined‐IMT, adjusted for age and sex. (A) Hazard ratio for stroke. (B) Hazard ratio for CVD events. CHS indicates Cardiovascular Health Study; HR, hazard ratio; and PRC‐USA, People's Republic of China‐United States of America;

Figure 6. Meta‐analysis of mean common carotid artery intima‐media thickness (mean CCA‐IMT) and cardiovascular disease (CVD).

Forest plots of hazard ratios per 1‐SD increment in mean CCA‐IMT, adjusted for age and sex. (A) Hazard ratio for stroke. (B) Hazard ratio for myocardial infarction. (C) Hazard ratio for CVD events. ARIC indicates Atherosclerosis Risk in Communities; BLSA, Beijing Longitudinal Study of Aging; CAPS, Carotid Atherosclerosis Progression Study; HNR, Heinz Nixdorf Recall; HR, hazard ratio; LitHiR, Lithuanian High Cardiovascular Risk; MDCS, Malmö Diet and Cancer Study; MI, myocardial infarction; and SMART, Second Manifestations of Arterial Disease.

Figure 7. Meta‐analysis of maximum common carotid artery intima‐media thickness (max CCA‐IMT) and cardiovascular disease (CVD).

Forest plots of hazard ratios per 1‐SD increment in maximum CCA‐IMT, adjusted for age and sex. (A) Hazard ratio for stroke. (B) Hazard ratio for myocardial infarction. (C) Hazard ratio for CVD events. CCCC indicates Chin‐Shan Community Cardiovascular Cohort Study; CHS, Cardiovascular Health Study; CVDFACTS, Cardiovascular Diseases Risk Factor Two‐Township Study; and HR, hazard ratio.