Left main coronary wall thickness correlates with the carotid intima media thickness and may provide a new marker of cardiovascular risk

Evaluation of carotid intima media thickness (C-IMT) by ultrasound is a well-established non-invasive tool to assess cardiovascular (CV) risk.1 Novel equipment has made evaluation easier, although still operator-sensitive, and with normal values not always transferable outside of the cohort of origin.2 Parallel evaluations with coronary calcium score (CCS) by computed tomography have been carried out, but there is no consensus on which is the technique that provides the most reliable data.3 Visualization of coronary wall thickness is presently achievable by transthoracic echography (TTE), a procedure carried out in real time with little cost. It is repeatable, does not expose the patient to radiation risk and, in preliminary studies, correlates with coronary events over a prolonged period of time.4 The present report was aimed at comparing, in a continued series of 301 individuals, C-IMT with the wall thickness of the left main coronary (LMCWT), determined by TTE. All evaluated patients were individuals referred to the Lipid Clinic, in whom C-IMT measurements are routinely carried out. Of these patients, 58% were on drug treatment, predominantly statins (32%), followed by ezetimibe (11%), fibrates (8%), Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies (2.3%) and nutraceuticals (14%). All participants signed an informed consent form and the procedures were approved by the Institutional Review Board. C-IMTs were measured with the electronic caliper of the MYLAB 70 XVG with a linear LA332 Probe (ESAOTE, Italy). The protocol requires determination of the mean C-IMTs of near and far walls of the right and left common carotids, bifurcations and internal carotids in three different projections, i.e. evaluating 36 segments per patient. C-IMTmean, an index of the extent of carotid atherosclerosis, is the average of C-IMTs at all the considered locations; conversely, C-IMTmax, representing an index of plaques, rather than of generalized wall thickening, is the single highest C-IMT. Coronary echography was carried out by the use of EPIQ 7C with an X5-1 Probe (Philips). The LMC was identified by evaluating projections from scanning, superior to the aortic valve. TTE visualization of the proximal LMC allows recording of the thickness of the LMC anterior (LMCaWT) and posterior walls (LMCpWT) together with the lumen diameter and percentage stenosis. Significant correlations for test–retest variability in the single operator were found: r = 0.81 and r = 0.85 for LMCaWT and LMCpWT, respectively. A comparative evaluation of C-IMTmax and LMCpWT in two participating patients is given in Figure 1(a) and (b). Panel (a) and (b): parallel evaluation of the carotid intima-media thickness (C-IMT)max versus left main coronary (LMC) wall thickness in two patients with increasing cardiovascular (CV) risk. Segments of the common carotid and LMC artery were taken from two patients with increasing CV risk, based on standard CV risk evaluation criteria. Panel (a): male smoker 34-year-old with blood pressure 100/70 mm Hg, low-density lipoprotein cholesterol (LDL-C) 151 mg/dl, high-density lipoprotein cholesterol (HDL-C) 50 mg/dl, triglyceride (TG) 77 mg/dl, no lipid lowering treatment. C-IMTmax 0.6 mm, LMC anterior wall thickness (LMCawt) 0.83 mm and LMC posterior wall thickness (LMCpwt) 0.85 mm. Panel (b): female smoker 68-year-old with blood pressure 120/60 mm Hg, LDL-C 147 mg/dl, HDL-C 58 mg/dl, TG 184 mg/dl, treated with fluvastatin 80 mg/day. C-IMTmax 2.6 mm, LMCawt 1.92 mm and LMCpwt 1.92 mm. Panel (c) and (d): multivariate models – observed and predicted values of LMCpWT. Multivariate linear regression models show a positive association between posterior wall coronary thickness and C-IMTmax and C-IMTmean. Values are adjusted for left coronary stenosis and diameter. C-IMTs and coronary wall thicknesses are expressed in mm. Panel (a) and (b): parallel evaluation of the carotid intima-media thickness (C-IMT)max versus left main coronary (LMC) wall thickness in two patients with increasing cardiovascular (CV) risk. Segments of the common carotid and LMC artery were taken from two patients with increasing CV risk, based on standard CV risk evaluation criteria. Panel (a): male smoker 34-year-old with blood pressure 100/70 mm Hg, low-density lipoprotein cholesterol (LDL-C) 151 mg/dl, high-density lipoprotein cholesterol (HDL-C) 50 mg/dl, triglyceride (TG) 77 mg/dl, no lipid lowering treatment. C-IMTmax 0.6 mm, LMC anterior wall thickness (LMCawt) 0.83 mm and LMC posterior wall thickness (LMCpwt) 0.85 mm. Panel (b): female smoker 68-year-old with blood pressure 120/60 mm Hg, LDL-C 147 mg/dl, HDL-C 58 mg/dl, TG 184 mg/dl, treated with fluvastatin 80 mg/day. C-IMTmax 2.6 mm, LMCawt 1.92 mm and LMCpwt 1.92 mm. Panel (c) and (d): multivariate models – observed and predicted values of LMCpWT. Multivariate linear regression models show a positive association between posterior wall coronary thickness and C-IMTmax and C-IMTmean. Values are adjusted for left coronary stenosis and diameter. C-IMTs and coronary wall thicknesses are expressed in mm. Patients were predominantly males (231 vs 70 females), women being older (median age 60 vs 51 years for males; Table 1). By assessing C-IMT variables and LMC thicknesses and widths, Spearman partial correlation coefficients, adjusted for age and body mass index (BMI), showed significant correlations (all p < 0.0001) between C-IMTmean (r = 0.31), C-IMTmax (r = 0.31) and C-IMTmean max (r = 0.33) with LMCpWT. Weaker correlations were found with the anterior wall thickness (r = 0.25, 0.23 and 0.25, respectively; all p < 0.001). Carotid thicknesses were positively related with LMC thicknesses, the most significant being that between internal carotid-IMTs and the LMCpWT (r = 0.38 and 0.35 for the internal carotid-IMTmean and -IMTmax, respectively). Correlations were confirmed by multivariate models, adjusted for LMC luminal diameter and stenosis, showing that LMCpWT was significantly and positively associated with IMTs of the whole carotid tree, i.e. C-IMTmax (Figure 1(c)), C-IMTmean (Figure 1(d)), and C-IMTmean max (β = 0.041; standard error (SE) = 0.013), as well as with internal carotid-IMTmax (β = 0.022; SE = 0.009) and internal carotid-IMTmean (β = 0.039; SE = 0.016). A similar trend was found for LMCaWT after adjusting for LMC stenosis and BMI: C-IMTmax (β = 0.131; SE = 0.027), C-IMTmean (β = 0.116; SE = 0.024), C-IMTmean max (β = 0.100; SE = 0.021), internal carotid-IMTmax (β = 0.065; SE = 0.016) and internal carotid-IMTmean (β = 0.133; SE = 0.025). Main characteristics of the selected patients. BIF-IMT: carotid artery bifurcation far wall intima-media thickness; BMI: body mass index; CC-IMT: common carotid-intima-media thickness; C-IMT: carotid-intima-media thickness; DPB: diastolic blood pressure; FPG: fasting plasma glucose; HDL-C: high-density lipoprotein cholesterol; ICA-IMT: internal carotid artery-intima-media thickness; LDL-C: low-density lipoprotein cholesterol; LMLdiam: left main luminal diameter; LMCaWT: left main coronary anterior wall thickness; LMCpWT: left main coronary posterior wall thickness; LMCst: left main coronary artery stenosis; Lp(a): lipoprotein (a); SBP: systolic blood pressure; TC: total cholesterol; TG: triglyceride; WC: waist circumference. Values of p indicate differences between males and females. Main characteristics of the selected patients. BIF-IMT: carotid artery bifurcation far wall intima-media thickness; BMI: body mass index; CC-IMT: common carotid-intima-media thickness; C-IMT: carotid-intima-media thickness; DPB: diastolic blood pressure; FPG: fasting plasma glucose; HDL-C: high-density lipoprotein cholesterol; ICA-IMT: internal carotid artery-intima-media thickness; LDL-C: low-density lipoprotein cholesterol; LMLdiam: left main luminal diameter; LMCaWT: left main coronary anterior wall thickness; LMCpWT: left main coronary posterior wall thickness; LMCst: left main coronary artery stenosis; Lp(a): lipoprotein (a); SBP: systolic blood pressure; TC: total cholesterol; TG: triglyceride; WC: waist circumference. Values of p indicate differences between males and females. The comparative evaluation of C-IMT, a well-established technique for the assessment of arterial conditions, vs wall thicknesses of the LMC, thus provided highly significant correlations, supporting the hypothesis that coronary wall thickness can be an informative parameter, indicative of local disease.5 The TTE method for the assessment of the LMC thickness is essentially applicable to every individual, provided the appropriate equipment and software are available. Although a large number of healthy individuals have been evaluated only by this method, the present study only reports findings from Lipid Clinic patients, where both C-IMT and TTE were determined. The presented results further indicate that thicknesses of the anterior and posterior coronary walls are positively associated with C-IMTmax and internal carotid artery-IMTmax when a multivariate model is considered; in particular, LMCpWT was linked to C-IMTmean max, i.e. the most predictive carotid ultrasonographic variable.6 A major application of coronary TTE is in the determination of coronary fractional flow reserve, of growing interest for the diagnosis of haemodynamically significant coronary stenoses. This is generally carried out by an invasive procedure, but also non-invasively by TTE, determining coronary flow velocity after vasodilation by adenosine or dipyridamole.7 A more promising diagnostic use of TTE may be, however, the measurement of coronary wall thickness. This can provide a direct assessment of coronary disease, and is also a tool for CV risk prediction in elderly individuals. Since the objective of predicting CV risk remains a mainstay in cardiovascular medicine, high C-IMT and in particular C-IMTmax, does appear to provide a reliable prediction.1 The IMPROVE (Carotid Intima Media Thickness (IMT) and IMTProgression as Predictors of Vascular Events in a High Risk European Population) study in Europe confirmed that CV risk is linearly associated with C-IMT in different nations, providing risk determination across ethnicities.8 Recently, an evaluation of the predictivity of common C-IMT variables, indicated that C-IMTmax and common C-IMTmean are mutually independent predictors of cerebrovascular events, whereas C-IMTmax is an independent predictor of coronary events.9 Finding a technique of relatively low cost, easy accessibility and possibly providing clinical information in a similar range as that given by more established invasive technologies, is a major objective in preventive medicine. In the present report, the highly significant association between carotid IMTs and thickness of the walls of the LMC, indicates that this latter may be a predictive marker of CV risk. The LMC thickness may be added as a non-invasive risk marker to the present discriminatory Systematic Coronary Risk Evaluation (SCORE) algorithm,10 improving risk stratification and cardiovascular risk prediction.11 Limitations of this approach are its dependence on operator skills and the selected population in a well-defined European area. Combination of carotid IMT findings and LMC wall thickness may be, however, of value in the determination of risk since, for example, severe carotid stenosis is associated with an increased angiographic prevalence of coronary stenosis.12 A practical use of coronary TTE is further suggested by the recent randomized controlled trial in angina patients (ORBITA study)13 reporting that patients with severe single-vessel disease do not attain a higher exercise time after a coronary intervention versus a placebo procedure. ORBITA study required two invasive procedures, whereas with TTE a significant stenosis in a single major coronary can be detected. The significant associations between carotid IMTs and thickness of the LMC walls support the conclusion that coronary wall thickness may be a marker of risk. This will require further, prospective studies in the examined patients. A study of this type is being carried out in participants of the present investigation. The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. The author(s) received no financial support for the research, authorship and/or publication of this article.