Low Ambient Temperature and Intracerebral Hemorrhage: The INTERACT2 Study

Danni Zheng, Hisatomi Arima, Shoichiro Sato, Antonio Gasparrini, Emma Heeley, Candice Delcourt, Serigne Lo, Yining Huang, Jiguang Wang, Christian Stapf, Thompson Robinson, Pablo Lavados, John Chalmers, Craig S Anderson, INTERACT2 investigators

Abstract

Background: Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale.

Methods: INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH (<6h of onset) and elevated systolic blood pressure (SBP, 150-220 mmHg) assigned to intensive (target SBP <140 mmHg) or guideline-recommended (SBP <180 mmHg) BP treatment. We linked individual level hourly temperature to baseline data of 1997 participants, and performed case-crossover analyses using a distributed lag non-linear model with 24h lag period to assess the association of ambient temperature and risk of ICH. Results were presented as overall cumulative odds ratios (ORs) and 95% CI.

Results: Low ambient temperature (≤10°C) was associated with increased risks of ICH: overall cumulative OR was 1.37 (0.99-1.91) for 10°C, 1.92 (1.31-2.81) for 0°C, 3.13 (1.89-5.19) for -10°C, and 5.76 (2.30-14.42) for -20°C, as compared with a reference temperature of 20°C.There was no clear relation of low temperature beyond three hours after exposure. Results were consistent in sensitivity analyses.

Conclusions: Exposure to low ambient temperature within several hours increases the risk of ICH.

Trial registration: ClinicalTrials.gov NCT00716079.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Bi-dimensional exposure-lag-response plot of intracerebral…
Fig 1. Bi-dimensional exposure-lag-response plot of intracerebral hemorrhage risk.
The exposure-response function was modeled with a natural cubic spline with internal knots placed at quartiles of ambient temperature (and a reference temperature of 20°C), and the lag-response function was modeled with a natural cubic spline with two equally spaced internal knots in log-scale.
Fig 2. Lag-exposure plots of intracerebral hemorrhage…
Fig 2. Lag-exposure plots of intracerebral hemorrhage risk for specific temperatures.
CI indicates confidence interval. Case (n) indicates the number of ICH events in each temperature exposure category.
Fig 3. Overall cumulative odds ratio plot…
Fig 3. Overall cumulative odds ratio plot of temperature effect.
Fig 4. Temporal pattern of intracerebral hemorrhage…
Fig 4. Temporal pattern of intracerebral hemorrhage onset and baseline systolic blood pressure level in patients.
ICH indicates intracerebral hemorrhage; SBP, systolic blood pressure.

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