Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis

Abstract

Background: Several imaging techniques may reveal calcification of the arterial wall or cardiac valves. Many studies indicate that the risk for cardiovascular disease is increased when calcification is present. Recent meta-analyses on coronary calcification and cardiovascular risk may be confounded by indication. Therefore, this meta-analysis was performed with extensive subgroup analysis to assess the overall cardiovascular risk of finding calcification in any arterial wall or cardiac valve when using different imaging techniques.

Methods and results: A meta-analysis of prospective studies reporting calcifications and cardiovascular end-points was performed. Thirty articles were selected. The overall odds ratios (95% confidence interval [CI]) for calcifications versus no calcifications in 218,080 subjects after a mean follow-up of 10.1 years amounted to 4.62 (CI 2.24 to 9.53) for all cause mortality, 3.94 (CI 2.39 to 6.50) for cardiovascular mortality, 3.74 (CI 2.56 to 5.45) for coronary events, 2.21 (CI 1.81 to 2.69) for stroke, and 3.41 (CI 2.71 to 4.30) for any cardiovascular event. Heterogeneity was largely explained by length of follow up and sort of imaging technique. Subgroup analysis of patients with end stage renal disease revealed a much higher odds ratio for any event of 6.22 (CI 2.73 to 14.14).

Conclusion: The presence of calcification in any arterial wall is associated with a 3-4-fold higher risk for mortality and cardiovascular events. Interpretation of the pooled estimates has to be done with caution because of heterogeneity across studies.

Keywords: calcification; cardiovascular risk; imaging; meta-analysis.

Figure 1

Odds ratios for mortality, all cause and cardiovascular, when calcification is present. Notes: Heterogeneity for all cause mortality chi-squared = 248.98 (d.f. = 8) p = 0.000; Heterogeneity for cardiovascular mortality chi-squared = 61.52 (d.f. = 8) p = 0.000.

Figure 2

Odds ratios for coronary events and stroke, when calcification is present. Notes: Heterogeneity for coronary events chi-squared = 154.86 (d.f. = 15) p = 0.000; Heterogeneity for stroke chi-squared = 21.67 (d.f. = 10) p = 0.017.

Figure 3

Risk for any cardiovascular event when calcification is present. Notes: Heterogeneity chi-squared = 198.94 (d.f. = 26) p = 0.000.

Figure 4

Results for any cardiovascular event stratified for imaging modality and follow up. Notes: Heterogeneity chi-squared in only CT studies = 22.32 (d.f. = 8) p = 0.004; Heterogeneity chi-squared in CT studies with follow up shorter than 5 years = 3.57 (d.f. = 6) p = 0.735; Heterogeneity chi-squared in CT studies with follow up longer than 5 years = 0.01 (d.f. = 1) p = 0.934.

Figure 5

Risk for any cardiovascular event due to calcification according to baseline risk. Notes: Heterogeneity in the low risk group chi-squared = 139.74 (d.f. = 14) p = 0.000; Heterogeneity in the intermediate risk group chi-squared = 55.79 (d.f. = 6) p = 0.000; Heterogeneity in the high risk group chi-squared = 1.52 (d.f. = 4) p = 0.823.

Figure 6

Subgroup analysis for renal insufficiency and diabetes mellitus. Notes: Heterogeneity in the renal insufficiency group chi-squared = 3.59 (d.f. = 3) p = 0.309; Heterogeneity in the diabetes mellitus group chi-squared = 0.98 (d.f. = 1) p = 0.322.

Figure 7

Funnel plot of standard error of log(OR) for any cardiovascular event. Notes: Begg’s funnel plot of published studies reporting any cardiovascular event. The fact that many studies are outside the 95% confidence interval, indicated by the sloping lines, is caused by heterogeneity of the studies.