Volume 84, May–June 2024, Pages 123-128Author links open overlay panel, , , , , , , Highlights•

Deep terminal negative of the P wave in V1 is significantly associated with higher risk of incident ischemic stroke independent of stroke risk factors including atrial fibrillation.

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The association of DTNPV1 with ischemic stroke could be explained by the impaired left atrial function in subjects with DTNPV1.

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Deep terminal negative of the P wave in V1 may have utility in identifying individuals who are at low risk of developing stroke.

AbstractBackground

Deep terminal negative of the P wave in V1 (DTNPV1) is a marker of left atrial remodeling. We aimed to evaluate the association of DTNPV1 with incident ischemic stroke.

Methods

The Atherosclerosis Risk in Communities study is a prospective community-based cohort study. All participants at visit 4 (1996–1998) except those with prevalent stroke, missing covariates, and missing or uninterpretable ECG were included. DTNPV1 was defined as the absolute value of the depth of the terminal negative phase >100 μV in the presence of biphasic P wave in V1. Association between DTNPV1 as a time-dependent exposure variable and incident ischemic stroke was evaluated. The accuracy of the prediction model consisting of DTNPV1 and CHA2DS2-VASc variables in predicting ischemic stroke was analyzed.

Results

Among 10,605 participants (63 ± 6 years, 56% women, 20% Black), 803 cases of ischemic stroke occurred over a median follow-up of 20.19 years. After adjusting for demographics, DTNPV1 was associated with an increased risk of stroke (HR 1.96, [95% CI 1.39–2.77]). After further adjusting for stroke risk factors, use of aspirin and anticoagulants, and time-dependent atrial fibrillation, DTNPV1 was associated with a 1.50-fold (95% CI 1.06–2.13) increased risk of stroke. When added to the CHA2DS2-VASc variables, DTNPV1 did not significantly improve stroke prediction as assessed by C-statistic. However, there was improvement in risk classification for participants who did not develop stroke.

Conclusion

DTNPV1 is significantly associated with higher risk of ischemic stroke. Since DTNPV1 is a simplified electrocardiographic parameter, it may help stroke prediction, a subject for further research.

Section snippetsStudy population

The Atherosclerosis Risk in Communities (ARIC) study is a prospective community-based cohort study that was designed to identify risk factors, cause, progression, and outcomes of atherosclerosis in the general population [8]. From 1987 to 1989, 15,792 participants were aged 45 to 64 recruited from 4 U.S. communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburban Minneapolis, Minnesota [8]. In this study, we included all participants (n = 11,656)

Results

Of 10,605 participants (age 63 ± 6 years, 56% women, 20% Black) in this study, there were 253 cases of prevalent DTNPV1 and 71 cases of incident DTNPV1. Table 1 shows that participants with prevalent DTNPV1 were older, more likely to be male and Black, and had higher blood pressure and more cardiovascular risk factors.

There were 803 ischemic stroke cases during a median follow-up of 20.2 years. An unadjusted restricted cubic spline (Fig. 3) displays a dose-response association (per μV unit)

Discussion

In this large prospective community-based cohort, we found that DTNPV1 was significantly associated with ischemic stroke independent of stroke risk factors including AF. We also observed that DTNPVI was associated with lower (worse) left atrial function. Hence, the association of DTNPV1 with ischemic stroke could be explained by the impaired left atrial function in subjects with DTNPV1. When we added DTNPV1 to CHA2DS2-VASc variables, there was no significant improvement in model discrimination

Conclusions

DTNPV1 is significantly associated with higher risk of ischemic stroke independent of stroke risk factors including AF. In people without prior AF or stroke, when added to CHA2DS2-VASc variables, DTNPV1 did not significantly improve stroke prediction. However, there is suggestive evidence to show that DTNPV1 may have utility in identifying individuals who are at low risk of developing stroke, a subject for further investigation.

Sources of funding and acknowledgement

The ARIC study has been funded with funds from the National Institutes of Health under Contract nos. (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005). LYC is supported by R01HL141288, R01HL126637, RF1 NS127266, R01 HL158022, R01AG075883, and K24HL155813. The authors thank ARIC staff and participants for their important contributions.

CRediT authorship contribution statement

Mingfang Li: Writing – review & editing, Writing – original draft, Investigation, Formal analysis, Conceptualization. Yuekai Ji: Methodology, Formal analysis, Data curation. Youmei Shen: Methodology, Conceptualization. Wendy Wang: Formal analysis, Data curation. Kamakshi Lakshminarayan: Writing – review & editing, Validation, Supervision, Conceptualization. Elsayed Z. Soliman: Supervision, Investigation. Minglong Chen: Supervision, Conceptualization. Lin Yee Chen: Writing – review & editing,

Declaration of competing interest

None.

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