In the present study, D-dimer was found to be a nonsignificant clinical indicator for detecting VAD. These findings are helpful in clinical practice because decisions based on laboratory data can directly affect outcomes.
From a pathophysiological viewpoint and contrarily to aortic dissection, in which degeneration of the aortic media is followed by an intimal tear, VAD is thought to occur as a subintimal dissection causing an intramural hematoma and leading to cerebral hypoperfusion, or as a subadventitial dissection creating an extraluminal pouch and leading to localized symptoms from the compression of adjacent nerves and their feeding vessels. Although both aortic dissection and VAD feature the separation of arterial wall layers,[20, 21] these mechanisms are not identical. This difference in pathogenesis can explain why D-dimer might not be useful in indicating VAD.
Another possible hypothesis is that D-dimer might reflect the influence of systemic circulation, which is determined by the size of the vessels and the length of exposure. In arterial etiology, for instance, aortic size is strongly correlated with dissection occurrence. Paruchuri et al. reported a mean ascending aortic diameter of 3.2 cm in non-diseased adults. Furthermore, more than 95% of the non-diseased population demonstrated an ascending aortic diameter under 3.9 cm, whereas nearly 90% of patients with aortic dissection demonstrated an ascending aortic diameter over 4.0 cm. Small arteries such as the vertebral artery (mean diameter 3.6–4.5 mm) or superior mesenteric artery (mean diameter 6.2–8.0 mm) might be too small to affect the coagulation system acutely even when they are dissected. By contrast, in venous etiology, DVT might be chronic enough to be reflected in laboratory tests. Although the results of this study could not establish an association between D-dimer and VAD, it was also conducted with a small sampling size, which are similar circumstances to those in previous studies on the superior mesenteric artery or cervical artery dissections.[25, 26, 27] Importantly, however, unelevated D-dimer levels do not exclude the possibility of VAD. Future studies with larger statistical power are therefore warranted.
On the other hand, the combination of a younger age and elevated blood pressure could raise the suspicion for VAD, which is known to have a high incidence among young adults. However, other clinical features vary from case to case. While some trigger events such as sports, cervical manipulation, trauma, intense sneezing, or coughing are indicated as clues,[28, 29] not every case presents such evident histories. In the present study, while all of the included patients with VAD presented with vertigo, other clinical features varied widely. Some trigger events were observed prior to the onset, but these involved less than half of the included patients. The time period between the events and the onsets also varied widely from two days to two months. Asking patients who are suffering of vertigo and heavy nausea about their headaches two months prior does not seem to be an effective way of narrowing down differential diagnoses in the ED. Neurological symptoms were the second most common presentation in our study, and yet, two patients were free from any neurological symptoms. The specific characteristics or symptoms that distinctly indicate VAD thus remain unelucidated.[2, 30]
Nevertheless, our study demonstrated the positive relation between blood pressure and VAD. In general, high blood pressure is unsurprising in stroke patients. Although the presence of HT was not significantly different between the two groups, HT is generally a strong risk factor for ischemic stroke. The physiologic response that maintains cerebral perfusion also results in increased blood pressure. However, the prevalence of HT is generally lower in young adults. Thus, disproportionate hypertension is unusual enough to raise suspicion for VAD. Although our sample size was not sufficient enough to guarantee the generalizability, the positive likelihood ratio (LR) of the combined criteria of age under 60 years and sBP over 160 mmHg was remarkable at 37.5. We believe in the simplicity of this criterion and the substantiality of the positive LR in clinical practice carries some significance worthy of further investigation. Thus, if a young patient visited an ED and presented with sudden-onset vertigo and/or headache with disproportionate hypertension, the patient should be endorsed for MRI even without any neurological symptoms or triggering events.
This study has several limitations. Firstly, this study was performed based on a single-center retrospective observational design. Although we reviewed eight years’ worth of medical records, only a small sample size could be obtained. Some of the parameters were possibly mis-analyzed as nonsignificant even with a fair prediction performance of the selected diagnostic model. Secondly, The proportion of the symptoms in our data varied with those in other studies.[1, 2] For example, according to the study by Lee VH et al, the most frequent initial symptom of cervical artery dissection, which includes both internal carotid artery dissection and vertebral artery dissection, was head and/or neck pain (80%). By contrast, in our study, as low as 36% of the included patients presented such symptoms. This discrepancy may imply the insufficient external validity of our findings. Thirdly, due to the retrospective study design, the data we could use were only extracted from medical records, which possibly made us miss important data points. Furthermore, many of the variables we used were unavailable from the records. Even with MICE, our results were not definitely conclusive or generalizable. Since rare diseases like VAD tend to be difficult to evaluate within one institute, multi-center studies with larger sample sizes are warranted in the future.
In conclusion, our findings did not demonstrate the usefulness of D-dimer for VAD diagnosis. Physicians should, however, keep in mind that unelevated D-dimer levels do not exclude the possibility of VAD. By contrast, disproportionate hypertension could possibly indicate VAD. Vital signs should be closely considered with the presenting symptoms. Future studies with larger-scale and multi-center designs should be undertaken to attain conclusive findings on the relationship between D-dimer and VAD, as well as to obtain more in-depth information on the mechanism of this disease.