Diabetes, hypertension, smoking, and hyperlipidemia as risk factors for spontaneous cervical artery dissection: Meta-analysis of case-control studies

Abstract

Background: Spontaneous cervical artery dissection (sCeAD) is an important cause of ischemic stroke in the young population and has a different cardiovascular risk profile from other causes of ischemic stroke. No study provided a comprehensive evidence for cardiovascular risk factors of sCeAD.
 Methods: We searched PubMed, MEDLINE, and Embase without date or language restrictions for relevant studies. Bibliographies of included studies were also searched. We included case-control studies where patients with sCeAD were on one arm, and controls were on the other arm. The investigated risk factors were diabetes, hypertension, smoking, and hyperlipidemia. Data extraction and quality assessment were performed independently by two reviewers.
 Results: Seventeen qualifying case-control studies were identified, comparing 2185 patients with sCeAD and 3185 healthy control subjects. Heterogeneity was low for diabetes, moderate for hypertension and hyperlipidemia, and high for smoking. The meta-analysis showed a significant association between hypertension and sCeAD [pooled odds ratio (OR) = 1.70, 95% confidence interval (CI): 1.40-2.07, P < 0.001]. There was no association between sCeAD and diabetes (pooled OR = 0.71, 95% CI: 0.50-1.01, P = 0.060) or smoking (pooled OR = 0.90, 95% CI: 0.68-1.20, P = 0.480). Hyperlipidemia was negatively-associated with sCeAD (OR = 0.65, 95% CI: 0.48-0.89, P = 0.007), but with sensitivity analysis, there was no association (OR = 0.72, 95% CI: 0.44-1.19, P = 0.200).
 Conclusion: The meta-analysis reveals that sCeAD has a significant association with hypertension and no association with smoking, diabetes, or hyperlipidemia. These results should direct future research towards exploring biological mechanism of hypertension-induced arterial dissection.

Risk Profile of Patients with Spontaneous Cervical Artery Dissection

“…Most of our findings, particularly on the relationship between traditional cardiovascular risk factors and sCeAD, are substantially in line with those of the only observational study conducted so far, including a large series of patients with sCeAD (which partly overlaps with the present one), a group of patients with non‐CeAD IS and a group of stroke‐free control subjects, 12 as well as with those of other smaller studies 3,13–15 . Overall, these results underscore a neutral or inverse association of classic pro‐atherosclerotic risk factors with disease risk in comparison with the 2 control groups, with the only notable exception of hypertension, which is confirmed in our analysis as a major susceptibility factor for sCeAD 3 . Similarly, the hypothesis of a link between migraine and sCeAD, based on the results of 2 previous large studies 16,17 and a few other smaller ones, 18 is essentially confirmed by the results of the present analysis.…”

“…3,[13][14][15] Overall, these results underscore a neutral or inverse association of classic proatherosclerotic risk factors with disease risk in comparison with the 2 control groups, with the only notable exception of hypertension, which is confirmed in our analysis as a major susceptibility factor for sCeAD. 3 Similarly, the hypothesis of a link between migraine and sCeAD, based on the results of 2 previous large studies 16,17 and a few other smaller ones, 18 is essentially confirmed by the results of the present analysis. Notwithstanding, our study represents a substantial step forward compared to previous analyses and some of their inherent methodological limitations.…”

“…Specifically, the variable migraine was not entered into the comprehensive analysis of the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) project, 12 whereas heterogeneity in the method of selection of stroke-free control subjects might theoretically represent a source of bias in the setting of an international multicenter study. 3 On the other hand, both the large studies focused on exploring the effect of migraine on the risk of disease lacked a group of stroke-free control subjects. 16,17 Unlike the previous registries, the IPSYS CeAD database allows us to adequately assess the strength of the association between all the individual variables and sCeAD within the same logistic model, and, hence, to define which among them is most likely to impact disease risk.…”

Hypertension is a possible risk factor for cervical artery dissection

“…In the first meta‐analysis we compared 2185 patients with CeAD and 3185 healthy controls. 3 There was a significant association of CeAD with hypertension and no association with smoking or diabetes. There was a negative association with hyperlipidaemia but sensitivity analysis with inclusion of studies that only compared total cholesterol between the CeAD and control groups showed no statistical association.…”

“…Many environmental and genetic risk factors have been proposed such as α1‐antitrypsin deficiency, hyperhomocysteinemia, recent infection, connective tissue disorders, styloid process length, and arterial tortuosity. 3 Few studies specifically addressed the link of CeAD with cardiovascular risk factors. In the Cervical Artery Dissections and Ischemic Patients (CADISP) group, which is a large international multicentre registry, the prevalence of smoking, diabetes and hypertension were statistically lower in CeAD than in non‐dissection ischemic stroke.…”