The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: Mediation analysis in SPRINT

Ashok Krishnaswami; Michael W. Rich; Min Ji Kwak; Parag Goyal; Daniel E. Forman; Abdulla A. Damluji; Matthew Solomon; Jamal S. Rana; Deborah M. Kado; Michelle C. Odden

doi:10.1093/eurjpc/zwad132

The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: Mediation analysis in SPRINT

Ashok Krishnaswami, Michael W. Rich, Min Ji Kwak, Parag Goyal, Daniel E. Forman, Abdulla A. Damluji, Matthew Solomon, Jamal S. Rana, Deborah M. Kado, Michelle C. Odden

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Aims: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. Methods and results: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. Conclusion: The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.

Original language	English
Pages (from-to)	996-1004
Number of pages	9
Journal	European Journal of Preventive Cardiology
Volume	30
Issue number	10
DOIs	https://doi.org/10.1093/eurjpc/zwad132
State	Published - Aug 1 2023

Keywords

All-cause mortality
Blood pressure treatment
CV mortality
Geriatrics
Hypertension
MACE
Mediation
Non-CV mortality
SAE

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10.1093/eurjpc/zwad132

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Krishnaswami, A., Rich, M. W., Kwak, M. J., Goyal, P., Forman, D. E., Damluji, A. A., Solomon, M., Rana, J. S., Kado, D. M., & Odden, M. C. (2023). The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: Mediation analysis in SPRINT. European Journal of Preventive Cardiology, 30(10), 996-1004. https://doi.org/10.1093/eurjpc/zwad132

@article{49fe8f03483341c28bbebdeb462c2527,

title = "The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: Mediation analysis in SPRINT",

abstract = "Aims: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. Methods and results: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. Conclusion: The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.",

keywords = "All-cause mortality, Blood pressure treatment, CV mortality, Geriatrics, Hypertension, MACE, Mediation, Non-CV mortality, SAE",

author = "Ashok Krishnaswami and Rich, {Michael W.} and Kwak, {Min Ji} and Parag Goyal and Forman, {Daniel E.} and Damluji, {Abdulla A.} and Matthew Solomon and Rana, {Jamal S.} and Kado, {Deborah M.} and Odden, {Michelle C.}",

year = "2023",

month = aug,

day = "1",

doi = "10.1093/eurjpc/zwad132",

language = "English",

volume = "30",

pages = "996--1004",

journal = "European Journal of Preventive Cardiology",

issn = "2047-4873",

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Krishnaswami, A, Rich, MW, Kwak, MJ, Goyal, P, Forman, DE, Damluji, AA, Solomon, M, Rana, JS, Kado, DM & Odden, MC 2023, 'The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: Mediation analysis in SPRINT', European Journal of Preventive Cardiology, vol. 30, no. 10, pp. 996-1004. https://doi.org/10.1093/eurjpc/zwad132

The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: Mediation analysis in SPRINT. / Krishnaswami, Ashok; Rich, Michael W.; Kwak, Min Ji et al.
In: European Journal of Preventive Cardiology, Vol. 30, No. 10, 01.08.2023, p. 996-1004.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality

T2 - Mediation analysis in SPRINT

AU - Krishnaswami, Ashok

AU - Rich, Michael W.

AU - Kwak, Min Ji

AU - Goyal, Parag

AU - Forman, Daniel E.

AU - Damluji, Abdulla A.

AU - Solomon, Matthew

AU - Rana, Jamal S.

AU - Kado, Deborah M.

AU - Odden, Michelle C.

PY - 2023/8/1

Y1 - 2023/8/1

N2 - Aims: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. Methods and results: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. Conclusion: The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.

AB - Aims: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. Methods and results: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. Conclusion: The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.

KW - All-cause mortality

KW - Blood pressure treatment

KW - CV mortality

KW - Geriatrics

KW - Hypertension

KW - MACE

KW - Mediation

KW - Non-CV mortality

KW - SAE

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U2 - 10.1093/eurjpc/zwad132

DO - 10.1093/eurjpc/zwad132

M3 - Article

C2 - 37185634

AN - SCOPUS:85166388150

SN - 2047-4873

VL - 30

SP - 996

EP - 1004

JO - European Journal of Preventive Cardiology

JF - European Journal of Preventive Cardiology

IS - 10

ER -

The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: Mediation analysis in SPRINT

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