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Clinical outcomes by atherosclerotic cardiovascular disease risk score and blood pressure level in high risk individuals with type 2 diabetes

Abstract

Clinical practice guidelines for patients with diabetes recommend using blood pressure (BP) and atherosclerotic cardiovascular disease (ASCVD) risk to guide antihypertensive treatment. While this approach directs treatment to patients who should receive a large ASCVD risk reduction, its effect on other outcomes is uncertain. The aim of this study was to assess the contributions of systolic blood pressure level (SBP) and predicted 10-year ASCVD risk using Pooled Cohort risk equations to the prediction of major macrovascular disease, death and major microvascular disease in patients with diabetes. Data came from 7426 individuals with type 2 diabetes (T2D) without macrovascular disease at baseline in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. The risk for major macrovascular events and death increased progressively across ASCVD risk categories. Compared to participants with 10-year predicted ASCVD risk <20% and SBP <130 mmHg, the hazard ratios (HRs) (95% confidence intervals (CIs)) associated with SBP ≥150 mmHg and 10-year predicted ASCVD risk <20%, 20–34% and ≥35% were 1.01 (0.58, 1.77), 1.90 (1.28, 2.84) and 2.82 (1.98, 4.01) for major macrovascular disease, respectively, and 0.83 (0.42, 1.62), 1.79 (1.13, 2.82) and 3.29 (2.22, 4.88) for death, respectively. The risk for major microvascular disease increased with BP regardless of ASCVD risk; HRs for SBP ≥150 mmHg and 10-year predicted ASCVD risk <20%, 20–34% and ≥35% vs. ASCVD risk <20% and SBP <130 mmHg were 1.52 (1.08,2.13), 1.47 (1.10, 1.96) and 1.23 (0.94, 1.60), respectively. ASCVD risk in addition to SBP improved the estimation of major macrovascular events and death but not major microvascular events among individuals with T2D.

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Fig. 1: Multiple adjusted* hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between atherosclerotic cardiovascular disease (ASCVD) risk score and systolic blood pressure (SBP) level cross-classification category and major macrovascular events, death and major microvascular events, in ADVANCE study participants without major macrovascular disease at baseline.

Data availability

Restrictions apply to the availability of these data, which were used by agreement of the ADVANCE steering committee for the current study, and so are not publicly available. R code for the c-statistic and NRI calculations is given in the Supplementary Material.

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Funding

The ADVANCE trial (ClinicalTrials.gov registration no. NCT00145925) was funded by grants from the National Health and Medical Research Council (NHMRC) of Australia (project grant ID 211086 and programme grant IDs 358395 and 571281) and from Servier. The study sponsors had no role in the design of the study, data collection, data analysis, data interpretation or the writing of the manuscript. Study data were not made available to the sponsors. The Management Committee, whose membership did not include any sponsor representatives, had final responsibility for the decision to submit for publication.

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Contributions

MW and JC conceived, designed and acquired the ADVANCE trial data. JC and JM conceived this study. KH conducted the statistical analyses, with advice from MW. KH wrote the initial drafts of the manuscript. All authors were involved in data interpretation. Drafts were revised for important scientific content by all authors. All authors gave final approval of the version to be published. KH is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Katie Harris.

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Competing interests

JC reports research grants from the NHMRC and from Servier for the ADVANCE trial and ADVANCE-ON post-trial follow-up, and honoraria for speaking about these studies at scientific meetings and support from NHMRC Programme Grant (APP1149987). MW reports consultancy fees from Amgen, Freeline and Kyowa Kirin and is supported by NHMRC grants APP1149987 and APP1174120. JM does not report any conflict of interest and reports attendance at the European Society of Hypertension, Barcelona, paid by ISORDIA (Switzerland) in 2018.

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Harris, K., Muntner, P., Woodward, M. et al. Clinical outcomes by atherosclerotic cardiovascular disease risk score and blood pressure level in high risk individuals with type 2 diabetes. J Hum Hypertens (2022). https://doi.org/10.1038/s41371-022-00661-5

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