Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. May 26, 2023; 15(5): 262-272
Published online May 26, 2023. doi: 10.4330/wjc.v15.i5.262
Pharmacoepidemiologic study of association between apparent treatment resistant hypertension, cardiovascular disease and interaction effect by sex and age
Julianne Theresa Nelson, Longjian Liu
Julianne Theresa Nelson, Longjian Liu, Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, United States
Author contributions: Nelson JT and Liu L contributed to the design and analysis of the study; Nelson JT prepared the written manuscript; Liu L critically reviewed and edited the manuscript.
Institutional review board statement: This study, using de-identified data from the National Heart, Lung, and Blood Institute, has been approved by Drexel University Institutional Review Board, No. 1608004781 (Principal Investigator: Longjian Liu).
Informed consent statement: This ALLHAT data is de-identified and publicly available for investigators to obtain through an IRB application process. Signed Informed Consent Forms are unavailable for the investigators conducting a secondary data analysis project.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The manuscript was prepared using ALLHAT Research Materials obtained from the National Heart, Lung, and Blood Institute (NHLBI).We are not allowed to share this dataset. For those who are interested in using this dataset, they need to apply for it from the NHLBI directly.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Longjian Liu, MD, MSc, PhD, Doctor, Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, 3215 Market ST, Philadelphia, PA 19104, United States. ll85@drexel.edu
Received: December 18, 2022
Peer-review started: December 18, 2022
First decision: March 1, 2023
Revised: March 31, 2023
Accepted: April 18, 2023
Article in press: April 18, 2023
Published online: May 26, 2023
Processing time: 152 Days and 6.5 Hours
ARTICLE HIGHLIGHTS
Research background

A Limited number of studies have been conducted to test the magnitudes of the association between apparent treatment resistant hypertension (aTRH) and risk of cardiovascular disease (CVD).

Research motivation

aTRH is significantly associated with the risk of CVD. It is important to understand whether age and sex significantly modify this association. Findings of the study could add new evidence to the body of literature, and provide new insights into further mechanism studies.

Research objectives

To investigate the association between aTRH and risk of CVD and examine whether sex and age modify this association.

Research methods

We applied an observational analysis study design using data from the United States Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT recruited participants (n = 25516) from 625 primary care settings throughout the United States, Canada, Puerto Rico, and United States Virgin Islands, aged 55 and older with hypertension and at least one additional risk factor for heart disease. aTRH was assessed from the year 2 visit. CVD event was defined as one of the following from the year 2 follow-up visit: Fatal or non-fatal myocardial infarction, coronary revascularization, angina, stroke, heart failure, or peripheral artery disease. Cox proportional hazards regression was used to examine the effect of aTRH on CVD risk. Potential modifications of sex and age on this association were examined on the multiplicative scale by interaction term and additive scale by joint effects and relative excess risk for interaction.

Research results

Of the total study participants, 5030 experienced a CVD event during a mean of 4.7 years follow-up. aTRH was associated with a 30% increase in risk of CVD compared to non-aTRH [hazards ratio (HR) = 1.3]. Sex and age modified this relationship on both multiplicative and additive scales independently. Stratified by sex, aTRH was associated with a 64% increase in risk of CVD in women, and a 13% increase in risk of CVD in men. Stratified by age, aTRH had a stronger impact on the risk of CVD in participants aged < 65 than it did in those aged ≥ 65. Significant two-way interactions of sex and aTRH, and age and aTRH on risk of CVD were observed (P < 0.05). The observed joint effect of aTRH and ages ≥ 65 years in males was less than what was expected for both additive and multiplicative models, although three-way interaction of sex, age, and aTRH on the risk of CVD and CHD did not reach a statistical significance (P > 0.05).

Research conclusions

aTRH was significantly associated with an increased risk of CVD and this association was modified by both sex and age.

Research perspectives

Further studies are warranted to test these mechanisms.