Negative interaction of fatty liver and hypertension on cardiovascular mortality in non-diabetic men: 34 years of follow-up

Abstract

Background and objectives

Fatty liver disease (FLD) and hypertension are separately associated with cardiovascular (CV) mortality. The two conditions are related in multiple ways. This work aimed to study the joint effect and interaction of FLD and hypertension in respect to overall and CV mortality.

Methods

The population-based cohort, Kuopio Ischaemic Disease Risk Factor Study, followed 1569 middle-aged non-diabetic Finnish men for 34 years. Considering adjustment for age, body mass index, smoking and alcohol consumption, separate and combined effects of FLD and hypertension and their interaction at the multiplicative and additive scales regarding all-cause and CV death were assessed using Cox proportional hazards models.

Results

FLD and hypertension coexisted in 8.54% of the men (n = 134). FLD and hypertension associated, independently and combined, with an increased hazard of all-cause and CV deaths. Non-CV mortality associated with FLD, but not with hypertension. We found a negative interaction between FLD and hypertension regarding the hazard of all-cause (relative excess risk due to interaction (RERI), −0.97; 95% confidence interval (CI), −1.65 to −0.28) and CV mortality (RERI, −1.74; 95% CI, −2.98 to −0.5). The interaction was also found on a multiplicative scale.

Conclusions

We found evidence of a negative interaction between FLD and hypertension in respect to CV mortality. We thus recommend adjusting for FLD or hypertension when studying the effect of the other condition on mortality or CV diseases in middle-aged men.

Keywords:

• Mortality
• cardiovascular disease
• hypertension
• heart disease risk factors
• fatty liver
• non-alcoholic fatty liver disease

Acknowledgements

Ethical approval and licenses: The study protocol was approved by the Research Ethics Committee of the University of Eastern Finland and the Research Ethics Committee Hospital District of Northern Savo, Finland (no. 143/97), and each participant gave written informed consent. The KIHD Study was performed in accordance with the Declaration of Helsinki. Cause of Death registry – Statistics Finland (license TK-53-1770-16). Care Register for Healthcare – National Institute for Health and Welfare (license THL/93/5.05.00/2013).

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

The University of Eastern Finland can be approached for requests of access to the KIHD dataset.