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. 2023 Nov 6:35:100759.
doi: 10.1016/j.lanepe.2023.100759. eCollection 2023 Dec.

Impact of the metabolic syndrome on cardiopulmonary morbidity and mortality in individuals with lung function impairment: a prospective cohort study of the Danish general population

Jacob Louis Marott  1   2 , Truls Sylvan Ingebrigtsen  1 , Yunus Çolak  1   2   3 , Hannu Kankaanranta  4   5   6 , Per Sigvald Bakke  7 , Jørgen Vestbo  8   9 , Børge Grønne Nordestgaard  1   2   10   11 , Peter Lange  1   3   12
Affiliations

Impact of the metabolic syndrome on cardiopulmonary morbidity and mortality in individuals with lung function impairment: a prospective cohort study of the Danish general population

Jacob Louis Marott et al. Lancet Reg Health Eur. .

Abstract

Background: Whether the metabolic syndrome plays a role for the prognosis of individuals with lung function impairment (preserved ratio impaired spirometry (PRISm) or airflow limitation) is unclear. We hypothesised that the metabolic syndrome in individuals with lung function impairment is associated with increased cardiopulmonary morbidity and mortality.

Methods: The Copenhagen General Population Study was initiated in 2003 based on a random sample of white men and women aged 20-100 years drawn from the Danish general population. The risk of ischemic heart disease/heart failure, respiratory disease, and all-cause mortality was analysed with Cox models adjusted for age, sex, current smoking, and asthma during 15 years of follow-up.

Findings: Among 106,845 adults, 86,159 had normal lung function, 6126 had PRISm, and 14,560 had airflow limitation. We observed 10,448 hospital admissions for ischemic heart disease/heart failure, 21,140 for respiratory disease, and 11,125 deaths. Individuals with versus individuals without the metabolic syndrome generally had higher 5-year absolute risk of all outcomes, including within those with normal lung function, mild-moderate-severe PRISm, and very mild-mild-moderate-severe airflow limitation alike. Compared to individuals without the metabolic syndrome and with normal lung function, those with both the metabolic syndrome and severe PRISm had hazard ratios of 3.74 (95% CI: 2.53-5.55; p < 0.0001) for ischemic heart disease/heart failure, 5.02 (3.85-6.55; p < 0.0001) for respiratory disease, and 5.32 (3.76-7.54; p < 0.0001) for all-cause mortality. Corresponding hazard ratios in those with both the metabolic syndrome and severe airflow limitation were 2.89 (2.34-3.58; p < 0.0001) for ischemic heart disease/heart failure, 5.98 (5.28-6.78; p < 0.0001) for respiratory disease, and 4.16 (3.50-4.95; p < 0.0001) for all-cause mortality, respectively. The metabolic syndrome explained 13% and 27% of the influence of PRISm or airflow limitation on ischemic heart disease/heart failure and all-cause mortality.

Interpretation: The metabolic syndrome conferred increased risk of cardiopulmonary morbidity and mortality at all levels of lung function impairment.

Funding: Danish Lung Foundation, Danish Heart Foundation, Capital Region of Copenhagen, and Boehringer Ingelheim. JV is supported by the NIHR Manchester BRC.

Keywords: Airflow limitation; Cardiopulmonary morbidity; Mortality; PRISm; Preserved ratio impaired spirometry.

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Conflict of interest statement

J.L.M. received an unrestricted grant from The Danish Lung Foundation in relation to the present work. T.S.I. received an advisory board fee from AstraZeneca. Y.Ç. received speaking fees from Sanofi Genzyme, AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim. H.K. reports funding from The Swedish Science Council, The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Foundation, The Tampere Tuberculosis Foundation, The Swedish ALF-funding, and The Finnish Anti-Tuberculosis Association Foundation outside the submitted work; being a committee member of the research council of the Swedish Heart and Lung Foundation; consulting fees from GlaxoSmithKline, AstraZeneca, MSD, Novartis, Orion Pharma, and Sanofi Genzyme; and speaking fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Orion Pharma. P.S.B. received lecture fees from AstraZeneca and Boehringer Ingelheim and advisory board fees from GlaxoSmithKline and AstraZeneca. J.V. received consulting fees from ALK, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Teva, as well as speaking fees from AstraZeneca, Boehringer Ingelheim, Chiesi, and GlaxoSmithKline and advisory board fees from AstraZeneca. P.L. received an unrestricted grant in relation to the present work from Boehringer Ingelheim; advisory board fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, and Sanofi; and speaking fees from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline. B.G.N. declares no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Absolute risk of ischemic heart disease or heart failure morbidity (Panel A), respiratory disease morbidity (Panel B), and all-cause mortality (Panel C) according to lung function and the metabolic syndrome with adjustment for age, sex, asthma, and smoking. Abbreviations: Normal, normal lung function; PRISm, preserved ratio impaired spirometry; AL, airflow limitation; IHD, ischemic heart disease; HF, heart failure. The severity of the lung function impairment was categorised in very mild (only AL), mild, moderate, and severe, based on FEV1 Z-scores.
Fig. 2
Fig. 2
Risk of ischemic heart disease or heart failure morbidity (Panels A and B), respiratory disease morbidity (Panels C and D), and all-cause mortality (Panels E and F) according to lung function in categories (Panels A, C, and E) and continuously (Panels B, D, and F) and the metabolic syndrome with adjustment for age, sex, asthma, and smoking. Abbreviations: Normal, normal lung function; PRISm, preserved ratio impaired spirometry; AL, airflow limitation; IHD, ischemic heart disease; HF, heart failure; CI, confidence interval. The severity of the lung function impairment was categorised in very mild (only AL), mild, moderate, and severe, based on FEV1 Z-scores.
Fig. 3
Fig. 3
Mediation analysis between the exposure lung function (both lung function impairment phenotype and FEV1 Z-score), the mediator the metabolic syndrome, and the outcomes ischemic heart disease or heart failure morbidity, respiratory disease morbidity, and all-cause mortality. Abbreviations: PRISm, preserved ratio impaired spirometry; IHD, ischemic heart disease; CI, confidence interval.
Fig. 4
Fig. 4
Low-grade systemic inflammation and risk of ischemic heart disease or heart failure morbidity, respiratory disease morbidity, and all-cause mortality in all individuals with PRISm or airflow limitation, or in those with or without the metabolic syndrome. All models were adjusted for age, sex, asthma, and smoking. Abbreviations: PRISm, preserved ratio impaired spirometry; HS-CRP, high-sensitivity C-reactive protein; IHD, ischemic heart disease; CI, confidence interval.
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