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Multi-state analysis of hypertension and mortality: application of semi-Markov model in a longitudinal cohort study
Azra Ramezankhani1, Michael J Blaha2, Mohammad Hassan Mirbolouk2
1Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Insights
Hypertension significantly increases mortality risk in individuals free of cardiovascular disease (CVD), with the 2017 ACC/AHA guidelines showing a reduced risk compared to older JNC7 criteria. The impact on mortality diminishes after a non-fatal CVD event.
Area of Science:
- Cardiology
- Public Health
- Epidemiology
Background:
- Previous research often examined hypertension's link to cardiovascular disease (CVD) and mortality as single endpoints.
- This study considers non-fatal CVD as an intermediate event in the progression to mortality.
Purpose of the Study:
- To investigate the impact of hypertension, defined by 2017 ACC/AHA and JNC7 guidelines, on CVD death and all-cause mortality.
- To analyze hypertension's effect on mortality risk considering non-fatal CVD as a transitional event.
Main Methods:
- Utilized multi-state semi-Markov models with three transitions for CVD death and all-cause mortality in 3002 Iranian adults (≥50 years) from 1999-2014.
- Employed multivariable Cox models to assess hypertension's impact on transition hazards and restricted mean survival time for life expectancy estimation.
Main Results:
- The 2017 ACC/AHA guideline increased hypertension prevalence from 43.3% to 68.6%.
- Hypertension significantly elevated risks of non-fatal CVD, CVD death, and all-cause mortality in CVD-free individuals (HRs ranging from 1.31 to 2.96).
- The association between hypertension and mortality was not significant after a non-fatal CVD event; hypertensive individuals experienced non-fatal CVD earlier.
Conclusions:
- Hypertension, by both JNC7 and ACC/AHA definitions, increases mortality risk in the CVD-free population, though the risk is attenuated with the ACC/AHA guideline.
- Hypertension reduces disease-free years and advances CVD onset, increasing time with these conditions.
- Post-non-fatal CVD, hypertension does not significantly impact mortality risk under either guideline.
Background:
Most previous research has studied the association of hypertension with cardiovascular disease (CVD) and all-cause mortality by focusing on the transition from the initial state to a single outcome. We investigated the impact of hypertension, defined according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) (new) and the Seventh Report of the Joint National Committee (JNC7) (old), on CVD death and all-cause mortality considering non-fatal CVD as an intermediate event between two CVD-free and mortality states.
Methods:
A total of 3002 Iranian population (47.4% men), aged ≥50 years were followed from 1999 to 2014. Two multi-state semi-Markov models with three transitions were defined for CVD death and all-cause mortality as two outcomes. The multivariable Cox model was used to estimate the effect of hypertension on transition hazards. The mean of 15-year life expectancy of participants in each transition was estimated using the restricted mean survival time.
Results:
The ACC/AHA guideline increased the prevalence of hypertension from 43.3 to 68.6%. Among CVD-free individuals, hypertension was significantly associated with increased risk of non-fatal CVD [Hazard Ratio, 1.52 (1.28-1.81) and 1.48 (1.21-1.80)], CVD death [2.96 (2.06-4.25) and 1.98 (1.30-3.04)] and all-cause mortality [1.64 (1.32-2.05) and 1.31 (1.01-1.69)] according the old and new guidelines, respectively. However, after incident non-fatal CVD, the association between hypertension and mortality events was not significant according to both definitions. Hypertensive participants experienced a first non-fatal CVD about 0.9 and 0.6 years earlier than normotensive population according to JNC7 and the 2017 ACC/AHA guidelines, respectively.
Conclusion:
Hypertension, according to JNC7 and the ACC/AHA guidelines, significantly increased the risk of mortality events among CVD-free population although the risk was attenuated using ACC/AHA guideline. Hypertension also decreased the number of years lived without CVD and early onset of CVD, and consequently, an increase in the time spent with these diseases. After non-fatal CVD, hypertension had no significant impact on mortality risk according to both guidelines.
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