We found that high baPWV levels (≥ 21.31 m/s) were associated with increased the short-term risk of first stroke among Chinese hypertensive adults, compared to low baPWV levels, supporting a reversed L-shaped association between baPWV and risk of first stroke. Sensitivity analyses showed consistent results. These results suggest that a baPWV of 21.31 m/s as the threshold for high risk in hypertensive patients. Furthermore, our study extends the results of previously published related studies by demonstrating that the association between baPWV and first stroke risk could be modified by SBP and DBP levels. Our findings warrant additional investigation.
Several previous studies have reported the association between baPWV and CVD and cerebrovascular diseases. A meta-analysis including 14673 Japanese participants without preexisting CVD established baPWV as an independent predictor of the risk of development of CVD[22]. Yong Bum Kim et al[16] used data from 1282 Korea participants and found that baPWV with both acute and chronic cerebral small vessel disease. Ting Li et al[23] indicated that increased baPWV were objective indicators of increased risk of ischemic stroke in patients with type 2 diabetes. These studies showed a linear association between baPWV and CVD. Of note, to our knowledge, only one study investigated the baPWV-stroke association in hypertension patients. Yun Song et al[12] conducted a prospective cohort study of 3310 Chinese hypertensive adults and found that high baPWV (≥ 20.85 m/s) was significantly associated with an increased risk of first stroke.
Our study provides some new insights into this field. First, we found that high baPWV levels (≥ 21.31 m/s) were associated with increased first stroke risk among Chinese hypertensive patients, supporting a threshold effect of baPWV on stroke. Toshiaki Ohkuma et al[24] proposed that the optimal cutoff value of baPWV for CVD in patients with hypertension was 18.3 m/s. Moreover, the threshold of baPWV varies by population and health conditions[25–28]. Our study findings have important clinical implications. To date, none of the stroke prevention guidelines have considered PWV as a predictor in risk assessment. Our findings raised that individuals with baPWV ≥ 20 m/s were at high risk of developing stroke among patients with hypertension. Several possible mechanisms for could explain the association between baPWV and incidence of first stroke. BaPWV, is not only considered as a marker of atherosclerosis, but also has a pathophysiologic role, which could promote the development of hypertension, macro/microvascular damage, and brain structural injury[29, 30]. Moreover, baPWV may be associated with stroke risk factors which in turn are important predictors of stroke[31]. Additionally, high baPWV is associated with the development of stroke through endothelial dysfunction, extracellular matrix disorder, elevated endothelial permeability, mechanical force on the inner wall of blood vessels, and vascular aging[19, 32]. Possibly, arterial stiffness may also increase in patients with endothelial dysfunction, oxidative stress, and inflammatory conditions, which could increase the risk of stroke[15, 33]. However, more studies are needed to confirm our findings and further elucidate the specific biological mechanisms.
Second, the magnitude of the effect of high baPWV on the risk of development of stroke was greater in hypertensive patients with well controlled BP. There was no association between baPWV and risk of stroke among patients with inadequate hypertension control. Consistent with our results, Toshiaki Ohkuma et al[22] also found that the association between baPWV and the risk of development of CVD was stronger in the participants without diabetes mellitus or hypertension than in those with either/both of these diseases. However, one previous study reported that participants with high baPWV and inadequate hypertension control had the highest risk of stroke compared with other groups. Differences in ethnics and methodological variations in baPWV measurements may possibly explain this discrepancy. Several considerations may explain the presence of this hypertension control paradox. While inadequate hypertension control is a major risk factor for stroke, subjects with the risk factor are also supposed to have higher baPWV levels in both the case group and the control group. Consequently, residual confoundings were inevitable when we analyzed association of high baPWV and risk of stroke in subjects with the factor. One hypothesis that has been proposed to explain this paradox is that by virtue of inadequate hypertension control, patients are offered earlier and more aggressive treatments to manage stroke risk factors. This may be related to the earlier, more intensive and closely monitored use of antiplatelet and anti-dyslipidaemic medications. Therefore, the findings may propose the applicability of baPWV measurement for prediction of stroke development, especially in subjects with a low atherosclerotic disease risk.
Potential limitations of our study should also be noted. First, the potential for residual confounding exists, as with all observational studies. Specifically, blood glucose and lipids could not be measured. We used the E-value sensitivity analysis to quantify the potential implications of unmeasured confounders and found that an unmeasured confounder was unlikely to explain the entirety of baPWV effect. Second, our study was underpowered to investigate the association between baPWV and risk of first hemorrhagic stroke. Third, the participants were all hypertensive from China; thus, the generalizability to general population or other ethics should be further verified. Fourth, the measurements of baPWV were only conducted at baseline. More frequent measurements of baPWV would provide more useful information. Fifth, follow-up time in the present study was short. However, the significant association between baPWV and risk of stroke was still observed, indicating high baPWV could increase the short-term risk of stroke. Despite these limitations, the strengths of the present study were the inclusion of a large number of participants, which allowed for sufficient statistical power to detect differences, the adjustments for confounders, and the subgroup analyses. Moreover, the threshold effect of baPWV on first stroke risk was observed. Furthermore, our results suggest that measurement of the baPWV may provide additional predictive information for future development of stroke in hypertensive patients with controlled BP.