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. 2021 Oct 28;19(1):258.
doi: 10.1186/s12916-021-02126-x.

Association between cardiometabolic disease multimorbidity and all-cause mortality in 2 million women and men registered in UK general practices

Dexter Canoy  1   2 , Jenny Tran  3 , Mariagrazia Zottoli  4 , Rema Ramakrishnan  3 , Abdelaali Hassaine  3 , Shishir Rao  3 , Yikuan Li  3 , Gholamreza Salimi-Khorshidi  3 , Robyn Norton  5 , Kazem Rahimi  3   6
Affiliations

Association between cardiometabolic disease multimorbidity and all-cause mortality in 2 million women and men registered in UK general practices

Dexter Canoy et al. BMC Med. .

Abstract

Background: Myocardial infarction (MI), stroke and diabetes share underlying risk factors and commonalities in clinical management. We examined if their combined impact on mortality is proportional, amplified or less than the expected risk separately of each disease and whether the excess risk is explained by their associated comorbidities.

Methods: Using large-scale electronic health records, we identified 2,007,731 eligible patients (51% women) and registered with general practices in the UK and extracted clinical information including diagnosis of myocardial infarction (MI), stroke, diabetes and 53 other long-term conditions before 2005 (study baseline). We used Cox regression to determine the risk of all-cause mortality with age as the underlying time variable and tested for excess risk due to interaction between cardiometabolic conditions.

Results: At baseline, the mean age was 51 years, and 7% (N = 145,910) have had a cardiometabolic condition. After a 7-year mean follow-up, 146,994 died. The sex-adjusted hazard ratios (HR) (95% confidence interval [CI]) of all-cause mortality by baseline disease status, compared to those without cardiometabolic disease, were MI = 1.51 (1.49-1.52), diabetes = 1.52 (1.51-1.53), stroke = 1.84 (1.82-1.86), MI and diabetes = 2.14 (2.11-2.17), MI and stroke = 2.35 (2.30-2.39), diabetes and stroke = 2.53 (2.50-2.57) and all three = 3.22 (3.15-3.30). Adjusting for other concurrent comorbidities attenuated these estimates, including the risk associated with having all three conditions (HR = 1.81 [95% CI 1.74-1.89]). Excess risks due to interaction between cardiometabolic conditions, particularly when all three conditions were present, were not significantly greater than expected from the individual disease effects.

Conclusion: Myocardial infarction, stroke and diabetes were associated with excess mortality, without evidence of any amplification of risk in people with all three diseases. The presence of other comorbidities substantially contributed to the excess mortality risks associated with cardiometabolic disease multimorbidity.

Keywords: Diabetes; Electronic health records; Mortality; Multimorbidity; Myocardial infarction; Stroke.

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Conflict of interest statement

KR, DC and JT have received support from the NIHR, British Heart Foundation, Oxford Martin School, Rhodes Trust or Clarendon Fund; other authors have no competing interest to declare. Funding organizations had no role in the design or conduct of the study; data collection, management, analysis and interpretation; and manuscript preparation, review or approval to submit for publication.

Figures

Fig. 1
Fig. 1
Risk of death according to cardiometabolic disease status at baseline. Risk estimates based on Cox regression with age as the underlying time variable and adjusted for sex with and without further adjustment for 53 additional comorbidities. The area of the square or circle is inversely proportional to the variance of the log risk. In the figure, error bars include the estimate (horizontal bar) and CI (vertical bar). CI confidence interval
Fig. 2
Fig. 2
Assessing interaction of two or more cardiometabolic conditions on mortality risk and departure from a multiplicative scale. All risk estimates based on Cox regression with age as underlying time variable and adjusted for sex with and without further adjustment for 53 additional comorbidities. Each coloured line represents expected risk estimates when no significant interaction (that is, no departure from multiplicativity) exists between two or more cardiometabolic diseases. HR hazard ratio, CI confidence interval, MI myocardial infarction
See this image and copyright information in PMC

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