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Preplanned Studies: Physical Activity and Different Recommendations Associated with the Dynamic Trajectory of Cardiometabolic Diseases — UK, 2006–2021

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  • Summary

    What is already known about this topic?

    Previous studies have illustrated the benefits of physical activity on cardiometabolic multimorbidity (CMM), while limited studies have concentrated on the trajectory of CMM progression.

    What is added by this report?

    Through multi-stage regression analysis, we found that physical activity could reduce the risk of CMM incidence. Participants initially free of cardiometabolic diseases (CMDs) may benefit more from engaging in recommended physical activity.

    What are the implications for public health practice?

    Adults, especially those initially free of CMDs, should engage in WHO-recommended physical activity as early as possible to prevent CMD incidence and further progression.

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  • Funding: Supported by the Bill & Melinda Gates Foundation (Grant Number: INV-016826)
  • [1] Han YT, Hu YZ, Yu CQ, Guo Y, Pei P, Yang L, et al. Lifestyle, cardiometabolic disease, and multimorbidity in a prospective Chinese study. Eur Heart J 2021;42(34):3374-84. https://academic.oup.com/eurheartj/article/42/34/3374/6333295.https://academic.oup.com/eurheartj/article/42/34/3374/6333295
    [2] Chen L, Cai M, Li HT, Wang XJ, Tian F, Wu YL, et al. Risk/benefit tradeoff of habitual physical activity and air pollution on chronic pulmonary obstructive disease: findings from a large prospective cohort study. BMC Med 2022;20(1):70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883705/pdf/12916_2022_Article_2274.pdf.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883705/pdf/12916_2022_Article_2274.pdf
    [3] IPAQ Research Committee. Guidelines for data processing and analysis of the international physical activity questionnaire (IPAQ)-short form. 2004. https://www.physio-pedia.com/images/c/c7/Quidelines_for_interpreting_the_IPAQ.pdf. [2022-11-18].https://www.physio-pedia.com/images/c/c7/Quidelines_for_interpreting_the_IPAQ.pdf
    [4] Chudasama YV, Khunti KK, Zaccardi F, Rowlands AV, Yates T, Gillies CL, et al. Physical activity, multimorbidity, and life expectancy: a UK Biobank longitudinal study. BMC Med 2019;17(1):108. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560907/pdf/12916_2019_Article_1339.pdf.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560907/pdf/12916_2019_Article_1339.pdf
    [5] Meira-Machado L, de Uña-Alvarez J, Cadarso-Suárez C, Andersen PK. Multi-state models for the analysis of time-to-event data. Stat Methods Med Res 2009;18(2):195-222. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692556/pdf/nihms-112498.pdf.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692556/pdf/nihms-112498.pdf
    [6] Tikkanen E, Gustafsson S, Ingelsson E. Associations of fitness, physical activity, strength, and genetic risk with cardiovascular disease: longitudinal analyses in the UK Biobank study. Circulation 2018;137(24):2583-91. https://www.ncbi.nlm.nih.gov/pubmed/29632216.https://www.ncbi.nlm.nih.gov/pubmed/29632216
    [7] Chudasama YV, Zaccardi F, Gillies CL, Dhalwani NN, Yates T, Rowlands AV, et al. Leisure-time physical activity and life expectancy in people with cardiometabolic multimorbidity and depression. J Intern Med 2020;287(1):87-99. https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/joim.12987?download=true.CrossRef
    [8] Albrecht GL, Devlieger PJ. The disability paradox: high quality of life against all odds. Soc Sci Med 1999;48(8):977-88. https://www.sciencedirect.com/science/article/pii/S0277953698004110?via%3Dihub.https://www.sciencedirect.com/science/article/pii/S0277953698004110?via%3Dihub
    [9] Zhao M, Veeranki SP, Magnussen CG, Xi B. Recommended physical activity and all cause and cause specific mortality in US adults: prospective cohort study. BMJ 2020;370:m2031. https://www.ncbi.nlm.nih.gov/pubmed/32611588.https://www.ncbi.nlm.nih.gov/pubmed/32611588
    [10] Powell KE, Paluch AE, Blair SN. Physical activity for health: What kind? How much? How intense? On top of what? Annu Rev Public Health 2011;32:349-65. https://www.annualreviews.org/doi/pdf/10.1146/annurev-publhealth-031210-101151.https://www.annualreviews.org/doi/pdf/10.1146/annurev-publhealth-031210-101151
  • TABLE 1.  Baseline characteristics of the participants by incident disease status during follow-up*.

    LevelsTotalFCMD survivorCMM survivorDeath with FCMDDeath with CMMDeath without CMDNon-cases
    Number of participants307,41123,2731,6204,0054759,772268,266
    Age at recruitment (years)55.46 (8.09)58.60 (7.34)59.92 (6.85)61.48 (6.46)63.08 (5.49)60.46 (6.89)54.87 (8.05)
    Years of follow-up11.92 (1.47)12.18 (0.83)12.22 (0.81)8.16 (3.19)9.45 (2.54)7.57 (3.26)12.12 (0.94)
    Sex
    Female164,962 (53.66)9,247 (39.73)568 (35.06)1,312 (32.76)140 (29.47)4,341 (44.42)149,354 (55.67)
    Male142,449 (46.34)14,026 (60.27)1,052 (64.94)2,693 (67.24)335 (70.53)5,431 (55.58)118,912 (44.33)
    Ethnicity
    White292,433 (95.13)21,980 (94.44)1,494 (92.22)3,880 (96.88)451 (94.95)9,512 (97.34)255,116 (95.10)
    Non-white14,173 (4.61)1,221 (5.25)119 (7.35)114 (2.85)24 (5.05)230 (2.35)12,465 (4.65)
    Unknown805 (0.26)72 (0.31)7 (0.43)11 (0.27)0 (0.00)30 (0.31)685 (0.26)
    BMI, kg/m2
    Normal106,760 (34.73)4,939 (21.22)200 (12.35)1,006 (25.12)84 (17.68)3,142 (32.15)97,389 (36.30)
    Underweight1,512 (0.49)67 (0.29)2 (0.12)29 (0.72)3 (0.63)100 (1.02)1,311 (0.49)
    Overweight134,015 (43.59)10,389 (44.64)688 (42.47)1,838 (45.89)207 (43.58)4,255 (43.54)116,638 (43.48)
    Obese65,124 (21.18)7,878 (33.85)730 (45.06)1,132 (28.26)181 (38.11)2,275 (23.28)52,928 (19.73)
    Education
    Higher degree159,486 (51.88)1,0492 (45.08)615 (37.96)1,632 (40.75)147 (30.95)4,338 (44.39)142,262 (53.03)
    School degree91,542 (29.78)6,367 (27.36)449 (27.72)1,018 (25.42)114 (24.00)2,551 (26.11)81,043 (30.21)
    Vocational degree17,332 (5.64)1,818 (7.81)122 (7.53)306 (7.64)41 (8.63)713 (7.30)14,332 (5.34)
    Other39,051 (12.70)4,596 (19.75)434 (26.79)1,049 (26.19)173 (36.42)2,170 (22.21)30,629 (11.42)
    Employment
    Paid195,130 (63.48)12,180 (52.34)735 (45.37)1,453 (36.28)137 (28.84)4,012 (41.06)176,613 (65.84)
    Retired23,384 (7.61)1,906 (8.19)189 (11.67)383 (9.56)56 (11.79)888 (9.09)19,962 (7.44)
    Unpaid88,897 (28.92)9,187 (39.47)696 (42.96)2,169 (54.16)282 (59.37)4,872 (49.86)71,691 (26.72)
    Smoking status
    Never174,910 (56.90)11,544 (49.60)722 (44.57)1,616 (40.35)152 (32.00)4,258 (43.57)156,618 (58.38)
    Previous102,212 (33.25)8,837 (37.97)655 (40.43)1,564 (39.05)217 (45.68)3,770 (38.58)87,169 (32.49)
    Current30,289 (9.85)2,892 (12.43)243 (15.00)825 (20.60)106 (22.32)1,744 (17.85)24,479 (9.12)
    Alcohol intake
    Never20,073 (6.53)1,951 (8.38)173 (10.68)350 (8.74)52 (10.95)789 (8.07)16,758 (6.25)
    Occasional64,093 (20.85)5,252 (22.57)423 (26.11)805 (20.10)100 (21.05)1,977 (20.23)55,536 (20.70)
    Moderate156,506 (50.91)11,025 (47.37)686 (42.35)1,781 (44.47)209 (44.00)4,416 (45.19)138,389 (51.59)
    Heavy66,739 (21.71)5,045 (21.68)338 (20.86)1,069 (26.69)114 (24.00)2,590 (26.50)57,583 (21.46)
    Household income
    Low50,701 (16.49)5,241 (22.52)452 (27.90)1,311 (32.73)185 (38.95)2,688 (27.51)40,824 (15.22)
    Moderate207,405 (67.47)14,522 (62.40)915 (56.48)2,118 (52.88)214 (45.05)5,592 (57.22)184,044 (68.61)
    High18,066 (5.88)869 (3.73)31 (1.91)108 (2.70)8 (1.68)293 (3.00)16,757 (6.25)
    Unknown31,239 (10.16)2,641 (11.35)222 (13.70)468 (11.69)68 (14.32)1,199 (12.27)26,641 (9.93)
    Fruit & vegetable intake
    Low87,443 (28.44)7,193 (30.91)490 (30.25)1,356 (33.86)151 (31.79)3,011 (30.81)75,242 (28.05)
    Moderate156,342 (50.86)11,360 (48.81)791 (48.83)1,859 (46.42)227 (47.79)4,807 (49.19)137,298 (51.18)
    High63,626 (20.70)4,720 (20.28)339 (20.93)790 (19.73)97 (20.42)1,954 (20.00)55,726 (20.77)
    Family history of CMM
    No240,798 (78.33)16,832 (72.32)1,089 (67.22)3,076 (76.80)344 (72.42)7,780 (79.62)211,677 (78.91)
    Yes66,613 (21.67)6,441 (27.68)531 (32.78)929 (23.20)131 (27.58)1,992 (20.38)56,589 (21.09)
    Physical activity level
    Low55,116 (17.93)4,721 (20.29)360 (22.22)841 (21.00)108 (22.74)1,920 (19.65)47,166 (17.58)
    Moderate125,837 (40.93)9,148 (39.31)630 (38.89)1,561 (38.98)179 (37.68)4,049 (41.43)110,270 (41.10)
    High126,458 (41.14)9,404 (40.41)630 (38.89)1,603 (40.02)188 (39.58)3,803 (38.92)110,830 (41.31)
    Meeting the 2017 physical activity guidelines§
    No54,427 (17.70)4,518 (19.41)328 (20.25)797 (19.90)100 (21.05)1,800 (18.42)46,884 (17.48)
    Yes252,984 (82.30)18,755 (80.59)1,292 (79.75)3,208 (80.10)375 (78.95)7,972 (81.58)221,382 (82.52)
    Meeting the WHO guidelines§
    No54,590 (17.76)4,651 (19.98)343 (21.17)821 (20.50)105 (22.11)1,908 (19.53)46,762 (17.43)
    Yes252,821 (82.24)18,622 (80.02)1,277 (78.83)3,184 (79.50)370 (77.89)7,864 (80.47)221,504 (82.57)
    Abbreviation: BMI=Body mass index; CMD=Cardiometabolic diseases; FCMD=First cardiometabolic disease; CMM=Cardiometabolic multimorbidity; 2017 Physical Activity Guidelines=the 2017 UK Physical Activity Guidelines; IHD=Ischemic heart disease; T2D=Type 2 diabetes.
    * Results are presented as mean (standard deviation) for continuous variables or number (percentage) for categorical variables.
    CMD include IHD, stroke, and T2D. CMM is defined as the co-occurrence of two or more diseases mentioned above.
    § Meeting the 2017 Physical Activity Guidelines means participants take 150 minutes of walking or moderate-intensity activity, 75 minutes of vigorous-intensity activity per week. WHO Guidelines mean participants take 150 minutes of moderate-intensity physical activity, 75 minutes of vigorous-intensity physical activity, or an equivalent combination of moderate- and vigorous-intensity physical activity.
    Download: CSV

    TABLE 2.  Associations between physical activity and FCMD, CMM, and all-cause death among 307,411 participants in the UK Biobank.

    Outcomes*Physical activityNo. of cases
    (total number)
    Model 1Model 2
    HR (95% CI)PHR (95% CI)P
    FCMDPhysical activity level
    Low6,030 (55,116)1.0001.000
    Moderate11,518 (125,837)0.800 (0.775, 0.825)< 0.0010.880 (0.853, 0.908)< 0.001
    High11,825 (126,458)0.798 (0.773, 0.823)< 0.0010.890 (0.862, 0.919)< 0.001
    Meeting the 2017 PA guidelines
    No5,743 (54,427)1.0001.000
    Yes23,630 (252,984)0.826 (0.803, 0.851)< 0.0010.906 (0.880, 0.933)< 0.001
    Meeting the WHO guidelines§
    No5,920 (54,590)1.0001.000
    Yes23,453 (252,821)0.805 (0.783, 0.829)< 0.0010.895 (0.869, 0.921)< 0.001
    CMMPhysical activity level
    Low468 (55,116)1.0001.000
    Moderate809 (125,837)0.718 (0.641, 0.805)< 0.0010.840 (0.749, 0.942)< 0.001
    High818 (126,458)0.702 (0.627, 0.787)< 0.0010.824 (0.734, 0.926)< 0.001
    Meeting the 2017 PA guidelines
    No428 (54,427)1.0001.000
    Yes1,667 (252,984)0.770 (0.692, 0.856)< 0.0010.887 (0.796, 0.988)0.029
    Meeting the WHO guidelines§
    No448 (54,590)1.0001.000
    Yes1,647 (252,821)0.738 (0.665, 0.819)< 0.0010.869 (0.781, 0.966)0.009
    All-cause deathPhysical activity level
    Low2,869 (55,116)1.0001.000
    Moderate5,789 (125,837)0.825 (0.789, 0.863)< 0.0010.872 (0.833, 0.912)< 0.001
    High5,594 (126,458)0.782 (0.747, 0.818)< 0.0010.819 (0.782, 0.857)< 0.001
    Meeting the 2017 PA guidelines
    No2,697 (54,427)1.0001.000
    Yes11,555 (252,984)0.974 (0.958, 0.990)0.0020.961 (0.945, 0.977)< 0.001
    Meeting the WHO guidelines§
    No2,834 (54,590)1.0001.000
    Yes11,418 (252,821)0.803 (0.771, 0.837)< 0.0010.851 (0.816, 0.887)< 0.001
    Note: “−” means not applicable.
    Abbreviation: FCMD=First cardiometabolic disease; CMM=Cardiometabolic multimorbidity; CMD=Cardiometabolic diseases; PA=Physical activity; No.=Number; HR=Hazard ratio; CI=Confidence interval; IHD=Ischemic heart disease; T2D=Type 2 diabetes.
    * CMD include IHD, stroke, and T2D. CMM is defined as the co-occurrence of two or more diseases mentioned above.
    Model 1 was adjusted for age (per 5-year interval), sex, and ethnicity; Model 2 was further adjusted for body mass index, total household income, employment, education, smoking status, alcohol intake, fruit and vegetable intake, and family history of CMM. All results were calculated by the traditional Cox proportional hazard regression models.
    § Meeting the 2017 Physical Activity Guidelines means participants take 150 minutes of walking or moderate-intensity activity or 75 minutes of vigorous-intensity activity per week. WHO Guidelines means participants take 150 minutes of moderate-intensity physical activity, 75 minutes of vigorous-intensity physical activity, or an equivalent combination of moderate- and vigorous-intensity physical activity.
    Download: CSV

    TABLE 3.  Associations between 5 transitions of CMM progression and physical activity levels among 307,411 participants in the UK Biobank.

    Transition*Physical activity levelNo. of cases (total number)HR (95% CI)P
    Baseline → FCMDLow6,030 (55,116)1.000
    Moderate11,518 (125,837)0.880 (0.853, 0.908)< 0.001
    High11,825 (126,458)0.892 (0.864, 0.920)< 0.001
    Baseline → DeathLow1,920 (55,116)1.000
    Moderate4,049 (125,837)0.886 (0.838, 0.936)< 0.001
    High3,803 (126,458)0.815 (0.771, 0.862)< 0.001
    FCMD → CMMLow468 (6,030)1.000
    Moderate809 (11,518)0.951 (0.848, 1.068)0.398
    High818 (11,825)0.942 (0.838, 1.059)0.315
    FCMD → DeathLow841 (6,030)1.000
    Moderate1,561 (11,518)0.908 (0.834, 0.988)0.026
    High1,603 (11,825)0.916 (0.841, 0.998)0.045
    CMM → DeathLow108 (468)1.000
    Moderate179 (809)0.882 (0.690, 1.127)0.314
    High188 (818)1.009 (0.790, 1.288)0.943
    Abbreviation: FCMD=First cardiometabolic disease; CMM=Cardiometabolic multimorbidity; HR=Hazard ratio; CI=Confidence interval; IHD=Ischemic heart disease; T2D=Type 2 diabetes; BMI=Body mass index.
    * CMD include IHD, stroke, and T2D. CMM is defined as co-occurrence of two or more diseases mentioned above. Trajectory pattern A consists of 5 transitions, including transitions from baseline to FCMD and all-cause death, transitions from FCMD to CMM and all-cause death, and to transition from CMM to all-cause death.
    Multivariable models were adjusted by age at recruitment (5-year interval) to sex, ethnicity, BMI, total household income, employment, education, smoking status, alcohol intake, fruit and vegetable intake, and family history of CMM.
    Download: CSV

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Physical Activity and Different Recommendations Associated with the Dynamic Trajectory of Cardiometabolic Diseases — UK, 2006–2021

View author affiliations

Summary

What is already known about this topic?

Previous studies have illustrated the benefits of physical activity on cardiometabolic multimorbidity (CMM), while limited studies have concentrated on the trajectory of CMM progression.

What is added by this report?

Through multi-stage regression analysis, we found that physical activity could reduce the risk of CMM incidence. Participants initially free of cardiometabolic diseases (CMDs) may benefit more from engaging in recommended physical activity.

What are the implications for public health practice?

Adults, especially those initially free of CMDs, should engage in WHO-recommended physical activity as early as possible to prevent CMD incidence and further progression.

  • 1. Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
  • 2. Department of Social Medicine and Health Service Management, Health Science Center, Shenzhen University, Shenzhen, Guangdong, China
  • Corresponding author:

    Zilong Zhang, zhangzilong@mail.sysu.edu.cn

  • Funding: Supported by the Bill & Melinda Gates Foundation (Grant Number: INV-016826)
  • Online Date: December 23 2022
    Issue Date: December 23 2022
    doi: 10.46234/ccdcw2022.232
  • While many studies have investigated the associations between physical activity and cardiometabolic diseases (CMDs), evidence remains scarce regarding the relationship between physical activity and different stages of cardiometabolic multimorbidity (CMM) progression. Using data from the United Kingdom (UK) Biobank study from 2006 to 2021, we adopted traditional Cox proportional hazard regression models and multi-state regression models to examine the associations between physical activity and CMM progression (Supplementary Figure S1). CMD was defined as any of the following three diseases, including ischemic heart disease (IHD) (I20 to I25), stroke (I60 to I64), and type 2 diabetes (T2D), (E11, and E14), which were determined via the International Classification of Diseases (10th Revision) (1). Incidence of the first CMD (FCMD) was identified as the earliest occurrence of any of these three diseases (IHD, stroke, and T2D), and incident of CMM was defined as the subsequent occurrence of any of the remaining CMDs. Inverse associations were observed between physical activity and almost all phases of CMM progression, albeit to different extents. The associations were stronger in transitions from baseline to FCMD [hazard ratio (HR): 0.880, 95% confidence intervals (CI): 0.853, 0.908 and HR: 0.892, 95% CI: 0.864, 0.920 for moderate and high physical activity levels]. Adults, especially those free of CMDs, showed the most conspicuous health benefits when meeting the World Health Organization (WHO) Guidelines.

    UK Biobank (UKB), an ongoing cohort study, recruited over half a million participants across the UK between 2006 and 2010. Data from the UK Biobank are available upon reasonable request (https://www.ukbiobank.ac.uk/). The study was approved by the Northwest Multi-Centre Research Ethics Committee (06/MRE08/65). Informed consent was obtained, and detailed information on the study protocols has been described elsewhere (2). All participants were followed up from recruitment to study until they were deceased, lost of subsequent follow-up from the health record, or March 31, 2021, whichever came first. A group of potential confounders were selected as presented in Table 1, and 307,411 participants were included in the final analysis (Supplementary Figure S2).

    Self-reported physical activity was categorized as low, moderate, and high levels according to widely-used criteria of the International Physical Activity Questionnaire (IPAQ). This criterion corresponds to <150 minutes/week, 150–750 minutes/week, and ≥750 minutes per week of moderate-intensity physical activity. The cut-off value of 600 MET-min/week is set by the WHO physical activity recommendations (3). Considering the more physically active cohort, four recommendations (Guideline Low, 2017 Physical Activity Guidelines, Guideline 300, and Guideline 450) were further defined to examine whether participants would harvest more benefits if they take higher-level physical activity (details of definitions of physical activity seen in Supplementary Methods) (4).

    Two incrementally adjusted Cox proportional hazard regression models were constructed to examine the associations between physical activity, FCMD, CMM, and all-cause death. The model plotted the data against follow-up time. Multi-state regression models (5) were used to assess the relationships between physical activity and the different phases of CMM progression, resulting in 5 transitions in trajectory pattern A (Supplementary Figure S1). Considering participants might enter the stages of FCMD/CMM or all-cause death simultaneously, we determined the entering date of the theoretically prior stage as the entering date of the theoretically latter stage minus 0.5 days (1). Several sensitivity analyses were conducted to examine the robustness of our results (Supplementary Methods) (6).

    All statistical analyses were conducted using R software (version 3.3.2, R Foundation for Statistical Computing, Vienna, Austria). A two-sided P value of <0.05 was considered statistically significant.

    A total of 307,411 participants with an average age of 55.46 [standard deviation (SD): 8.09] years at baseline were included (Table 1). During a mean follow-up of 11.92 years, 29,373 (9.56%) participants developed at least one CMD (3.67% were self-reported cases); among them, 7.13% developed CMM later, and 22.67% died from CMM eventually (Supplementary Figure S1).

    LevelsTotalFCMD survivorCMM survivorDeath with FCMDDeath with CMMDeath without CMDNon-cases
    Number of participants307,41123,2731,6204,0054759,772268,266
    Age at recruitment (years)55.46 (8.09)58.60 (7.34)59.92 (6.85)61.48 (6.46)63.08 (5.49)60.46 (6.89)54.87 (8.05)
    Years of follow-up11.92 (1.47)12.18 (0.83)12.22 (0.81)8.16 (3.19)9.45 (2.54)7.57 (3.26)12.12 (0.94)
    Sex
    Female164,962 (53.66)9,247 (39.73)568 (35.06)1,312 (32.76)140 (29.47)4,341 (44.42)149,354 (55.67)
    Male142,449 (46.34)14,026 (60.27)1,052 (64.94)2,693 (67.24)335 (70.53)5,431 (55.58)118,912 (44.33)
    Ethnicity
    White292,433 (95.13)21,980 (94.44)1,494 (92.22)3,880 (96.88)451 (94.95)9,512 (97.34)255,116 (95.10)
    Non-white14,173 (4.61)1,221 (5.25)119 (7.35)114 (2.85)24 (5.05)230 (2.35)12,465 (4.65)
    Unknown805 (0.26)72 (0.31)7 (0.43)11 (0.27)0 (0.00)30 (0.31)685 (0.26)
    BMI, kg/m2
    Normal106,760 (34.73)4,939 (21.22)200 (12.35)1,006 (25.12)84 (17.68)3,142 (32.15)97,389 (36.30)
    Underweight1,512 (0.49)67 (0.29)2 (0.12)29 (0.72)3 (0.63)100 (1.02)1,311 (0.49)
    Overweight134,015 (43.59)10,389 (44.64)688 (42.47)1,838 (45.89)207 (43.58)4,255 (43.54)116,638 (43.48)
    Obese65,124 (21.18)7,878 (33.85)730 (45.06)1,132 (28.26)181 (38.11)2,275 (23.28)52,928 (19.73)
    Education
    Higher degree159,486 (51.88)1,0492 (45.08)615 (37.96)1,632 (40.75)147 (30.95)4,338 (44.39)142,262 (53.03)
    School degree91,542 (29.78)6,367 (27.36)449 (27.72)1,018 (25.42)114 (24.00)2,551 (26.11)81,043 (30.21)
    Vocational degree17,332 (5.64)1,818 (7.81)122 (7.53)306 (7.64)41 (8.63)713 (7.30)14,332 (5.34)
    Other39,051 (12.70)4,596 (19.75)434 (26.79)1,049 (26.19)173 (36.42)2,170 (22.21)30,629 (11.42)
    Employment
    Paid195,130 (63.48)12,180 (52.34)735 (45.37)1,453 (36.28)137 (28.84)4,012 (41.06)176,613 (65.84)
    Retired23,384 (7.61)1,906 (8.19)189 (11.67)383 (9.56)56 (11.79)888 (9.09)19,962 (7.44)
    Unpaid88,897 (28.92)9,187 (39.47)696 (42.96)2,169 (54.16)282 (59.37)4,872 (49.86)71,691 (26.72)
    Smoking status
    Never174,910 (56.90)11,544 (49.60)722 (44.57)1,616 (40.35)152 (32.00)4,258 (43.57)156,618 (58.38)
    Previous102,212 (33.25)8,837 (37.97)655 (40.43)1,564 (39.05)217 (45.68)3,770 (38.58)87,169 (32.49)
    Current30,289 (9.85)2,892 (12.43)243 (15.00)825 (20.60)106 (22.32)1,744 (17.85)24,479 (9.12)
    Alcohol intake
    Never20,073 (6.53)1,951 (8.38)173 (10.68)350 (8.74)52 (10.95)789 (8.07)16,758 (6.25)
    Occasional64,093 (20.85)5,252 (22.57)423 (26.11)805 (20.10)100 (21.05)1,977 (20.23)55,536 (20.70)
    Moderate156,506 (50.91)11,025 (47.37)686 (42.35)1,781 (44.47)209 (44.00)4,416 (45.19)138,389 (51.59)
    Heavy66,739 (21.71)5,045 (21.68)338 (20.86)1,069 (26.69)114 (24.00)2,590 (26.50)57,583 (21.46)
    Household income
    Low50,701 (16.49)5,241 (22.52)452 (27.90)1,311 (32.73)185 (38.95)2,688 (27.51)40,824 (15.22)
    Moderate207,405 (67.47)14,522 (62.40)915 (56.48)2,118 (52.88)214 (45.05)5,592 (57.22)184,044 (68.61)
    High18,066 (5.88)869 (3.73)31 (1.91)108 (2.70)8 (1.68)293 (3.00)16,757 (6.25)
    Unknown31,239 (10.16)2,641 (11.35)222 (13.70)468 (11.69)68 (14.32)1,199 (12.27)26,641 (9.93)
    Fruit & vegetable intake
    Low87,443 (28.44)7,193 (30.91)490 (30.25)1,356 (33.86)151 (31.79)3,011 (30.81)75,242 (28.05)
    Moderate156,342 (50.86)11,360 (48.81)791 (48.83)1,859 (46.42)227 (47.79)4,807 (49.19)137,298 (51.18)
    High63,626 (20.70)4,720 (20.28)339 (20.93)790 (19.73)97 (20.42)1,954 (20.00)55,726 (20.77)
    Family history of CMM
    No240,798 (78.33)16,832 (72.32)1,089 (67.22)3,076 (76.80)344 (72.42)7,780 (79.62)211,677 (78.91)
    Yes66,613 (21.67)6,441 (27.68)531 (32.78)929 (23.20)131 (27.58)1,992 (20.38)56,589 (21.09)
    Physical activity level
    Low55,116 (17.93)4,721 (20.29)360 (22.22)841 (21.00)108 (22.74)1,920 (19.65)47,166 (17.58)
    Moderate125,837 (40.93)9,148 (39.31)630 (38.89)1,561 (38.98)179 (37.68)4,049 (41.43)110,270 (41.10)
    High126,458 (41.14)9,404 (40.41)630 (38.89)1,603 (40.02)188 (39.58)3,803 (38.92)110,830 (41.31)
    Meeting the 2017 physical activity guidelines§
    No54,427 (17.70)4,518 (19.41)328 (20.25)797 (19.90)100 (21.05)1,800 (18.42)46,884 (17.48)
    Yes252,984 (82.30)18,755 (80.59)1,292 (79.75)3,208 (80.10)375 (78.95)7,972 (81.58)221,382 (82.52)
    Meeting the WHO guidelines§
    No54,590 (17.76)4,651 (19.98)343 (21.17)821 (20.50)105 (22.11)1,908 (19.53)46,762 (17.43)
    Yes252,821 (82.24)18,622 (80.02)1,277 (78.83)3,184 (79.50)370 (77.89)7,864 (80.47)221,504 (82.57)
    Abbreviation: BMI=Body mass index; CMD=Cardiometabolic diseases; FCMD=First cardiometabolic disease; CMM=Cardiometabolic multimorbidity; 2017 Physical Activity Guidelines=the 2017 UK Physical Activity Guidelines; IHD=Ischemic heart disease; T2D=Type 2 diabetes.
    * Results are presented as mean (standard deviation) for continuous variables or number (percentage) for categorical variables.
    CMD include IHD, stroke, and T2D. CMM is defined as the co-occurrence of two or more diseases mentioned above.
    § Meeting the 2017 Physical Activity Guidelines means participants take 150 minutes of walking or moderate-intensity activity, 75 minutes of vigorous-intensity activity per week. WHO Guidelines mean participants take 150 minutes of moderate-intensity physical activity, 75 minutes of vigorous-intensity physical activity, or an equivalent combination of moderate- and vigorous-intensity physical activity.

    Table 1.  Baseline characteristics of the participants by incident disease status during follow-up*.

    In traditional Cox regression analysis, higher physical activity levels were associated with lower FCMD, CMM, and all-cause mortality incidence (Table 2). For moderate physical activity level, the fully adjusted HRs [95% confidence intervals (CI)] relative to low physical activity level were 0.880 (0.853, 0.908) for FCDM, 0.840 (0.749, 0.942) for CMM, and 0.872 (0.833, 0.912) for all-cause mortality, respectively.

    Outcomes*Physical activityNo. of cases
    (total number)
    Model 1Model 2
    HR (95% CI)PHR (95% CI)P
    FCMDPhysical activity level
    Low6,030 (55,116)1.0001.000
    Moderate11,518 (125,837)0.800 (0.775, 0.825)< 0.0010.880 (0.853, 0.908)< 0.001
    High11,825 (126,458)0.798 (0.773, 0.823)< 0.0010.890 (0.862, 0.919)< 0.001
    Meeting the 2017 PA guidelines
    No5,743 (54,427)1.0001.000
    Yes23,630 (252,984)0.826 (0.803, 0.851)< 0.0010.906 (0.880, 0.933)< 0.001
    Meeting the WHO guidelines§
    No5,920 (54,590)1.0001.000
    Yes23,453 (252,821)0.805 (0.783, 0.829)< 0.0010.895 (0.869, 0.921)< 0.001
    CMMPhysical activity level
    Low468 (55,116)1.0001.000
    Moderate809 (125,837)0.718 (0.641, 0.805)< 0.0010.840 (0.749, 0.942)< 0.001
    High818 (126,458)0.702 (0.627, 0.787)< 0.0010.824 (0.734, 0.926)< 0.001
    Meeting the 2017 PA guidelines
    No428 (54,427)1.0001.000
    Yes1,667 (252,984)0.770 (0.692, 0.856)< 0.0010.887 (0.796, 0.988)0.029
    Meeting the WHO guidelines§
    No448 (54,590)1.0001.000
    Yes1,647 (252,821)0.738 (0.665, 0.819)< 0.0010.869 (0.781, 0.966)0.009
    All-cause deathPhysical activity level
    Low2,869 (55,116)1.0001.000
    Moderate5,789 (125,837)0.825 (0.789, 0.863)< 0.0010.872 (0.833, 0.912)< 0.001
    High5,594 (126,458)0.782 (0.747, 0.818)< 0.0010.819 (0.782, 0.857)< 0.001
    Meeting the 2017 PA guidelines
    No2,697 (54,427)1.0001.000
    Yes11,555 (252,984)0.974 (0.958, 0.990)0.0020.961 (0.945, 0.977)< 0.001
    Meeting the WHO guidelines§
    No2,834 (54,590)1.0001.000
    Yes11,418 (252,821)0.803 (0.771, 0.837)< 0.0010.851 (0.816, 0.887)< 0.001
    Note: “−” means not applicable.
    Abbreviation: FCMD=First cardiometabolic disease; CMM=Cardiometabolic multimorbidity; CMD=Cardiometabolic diseases; PA=Physical activity; No.=Number; HR=Hazard ratio; CI=Confidence interval; IHD=Ischemic heart disease; T2D=Type 2 diabetes.
    * CMD include IHD, stroke, and T2D. CMM is defined as the co-occurrence of two or more diseases mentioned above.
    Model 1 was adjusted for age (per 5-year interval), sex, and ethnicity; Model 2 was further adjusted for body mass index, total household income, employment, education, smoking status, alcohol intake, fruit and vegetable intake, and family history of CMM. All results were calculated by the traditional Cox proportional hazard regression models.
    § Meeting the 2017 Physical Activity Guidelines means participants take 150 minutes of walking or moderate-intensity activity or 75 minutes of vigorous-intensity activity per week. WHO Guidelines means participants take 150 minutes of moderate-intensity physical activity, 75 minutes of vigorous-intensity physical activity, or an equivalent combination of moderate- and vigorous-intensity physical activity.

    Table 2.  Associations between physical activity and FCMD, CMM, and all-cause death among 307,411 participants in the UK Biobank.

    Multi-state regression analyses generated similar results regarding the results yielded by traditional Cox regression models (Table 3). The inverse associations were found between physical activity and almost all transitions in CMM progression, as the HRs (95% CIs) of transition from baseline to death were 0.886 (0.838, 0.936) and 0.815 (0.771, 0.862) for moderate and high level of physical activity. Meeting the WHO Guidelines showed the most conspicuous benefits among all five transitions (Supplementary Table S2). All our findings remained substantially stable after conducting several sensitivity analyses (Supplementary Tables S2S3).

    Transition*Physical activity levelNo. of cases (total number)HR (95% CI)P
    Baseline → FCMDLow6,030 (55,116)1.000
    Moderate11,518 (125,837)0.880 (0.853, 0.908)< 0.001
    High11,825 (126,458)0.892 (0.864, 0.920)< 0.001
    Baseline → DeathLow1,920 (55,116)1.000
    Moderate4,049 (125,837)0.886 (0.838, 0.936)< 0.001
    High3,803 (126,458)0.815 (0.771, 0.862)< 0.001
    FCMD → CMMLow468 (6,030)1.000
    Moderate809 (11,518)0.951 (0.848, 1.068)0.398
    High818 (11,825)0.942 (0.838, 1.059)0.315
    FCMD → DeathLow841 (6,030)1.000
    Moderate1,561 (11,518)0.908 (0.834, 0.988)0.026
    High1,603 (11,825)0.916 (0.841, 0.998)0.045
    CMM → DeathLow108 (468)1.000
    Moderate179 (809)0.882 (0.690, 1.127)0.314
    High188 (818)1.009 (0.790, 1.288)0.943
    Abbreviation: FCMD=First cardiometabolic disease; CMM=Cardiometabolic multimorbidity; HR=Hazard ratio; CI=Confidence interval; IHD=Ischemic heart disease; T2D=Type 2 diabetes; BMI=Body mass index.
    * CMD include IHD, stroke, and T2D. CMM is defined as co-occurrence of two or more diseases mentioned above. Trajectory pattern A consists of 5 transitions, including transitions from baseline to FCMD and all-cause death, transitions from FCMD to CMM and all-cause death, and to transition from CMM to all-cause death.
    Multivariable models were adjusted by age at recruitment (5-year interval) to sex, ethnicity, BMI, total household income, employment, education, smoking status, alcohol intake, fruit and vegetable intake, and family history of CMM.

    Table 3.  Associations between 5 transitions of CMM progression and physical activity levels among 307,411 participants in the UK Biobank.

    • Our study investigated the impact of physical activity levels and recommendations on different trajectories of CMM progression. The results of both traditional Cox regression and multi-state regression analyses yielded the inverse associations between physical activity and CMD incidence and further progression, albeit to different degrees. More substantial impacts of physical activity were found on transitions from baseline to FCMD and all-cause death. The WHO Guidelines seemed to possess more pronounced health benefits than the other four recommendations.

      In traditional Cox regression analyses, increasing physical activity levels were associated with lower FCMD, CMM, and death incidence. A stronger association was found in transition from the baseline to CMM. The findings differed from previous studies reporting a more beneficial role physical activity played in the transition from the baseline to single CMD than CMM (7). The heterogeneity might be due to multiple factors, albeit largely unclear. First, CMM incidence in traditional Cox regression models consisted of several transitions in multi-state regression models. Different transitions might have reshaped the characteristics of the study population, consequently leading to different effect estimates. Second, as Albrecht et al. suggested (8), the disability paradox might largely influence the fundamental relationship between life quality and diseases. The influence of physical activity might thus be exaggerated as adults may be influenced to have higher levels of physical activity after being diagnosed with CMDs. Notably, such speculation seemed contradictory to the findings in multi-state regression models, where stronger associations were observed in the transition from the baseline to FCMD than in the transition from FCMD to CMM. Further studies are warranted to confirm our findings and to investigate the underlying mechanisms.

      Inverse relationships between physical activity and almost all the transition incidences were observed in multi-state regression models, with stronger associations observed in transitions from baseline to FCMD/death. In contrast, a recent study of the China Kadoorie Biobank (CKB) found that physical inactivity significantly impacted the transition from FCMD to death/CMM (1). Foremost, the percentage of low physical activity levels was relatively more prominent in the CKB (about 50%) than UKB (about 20%) (1), indicating the Chinese adults were more physically inactive, albeit the CKB participants might not represent the general Chinese population well. Physical activity has been well-confirmed to be associated with lower risks of numerous chronic diseases (9). The relatively low percentage of taking physical activity in China would therefore imply more significant health benefits if Chinese adults could take more physical activity. Furthermore, a higher prevalence of CMDs in CKB (19%) than in UKB (9.55%) indicated that the Chinese population was more sensitive to adverse health outcomes, such as CMM. Physical activity could play a more notable role in CMM progression in CKB than UKB, considering the more vulnerable group of Chinese adults. Therefore, Chinese policymakers should encourage adults to take physical activity actively to help lower the risks of CMM in the Chinese population.

      Meeting the WHO Guidelines showed the most notable benefits on almost all transitions compared with other higher-level recommendations. It was different from the current physical activity recommendations suggesting that adults already with chronic diseases should take more physical activity. The difference could be interpreted by the fact that the health benefits of increasing physical activity tend to hit a plateau when adults have met the WHO Guidelines (10).

      Several limitations should be noted. First, we only adopted information at baseline levels. Changes in physical activity and other covariates over the follow-up may influence the estimates. However, we further conducted an additional analysis in a sub-sample of participants (n=15,894), finding most participants (63%) maintained their physical activity level. The distribution of physical activity levels among participants with or without CMDs was similar (Supplementary Table S1), indicating the changes were non-differentially distributed, our results would not be substantially affected. Second, for those diagnosed with two or more CMDs on the same date, we determined the entering date as the entering date of the theoretically latter stage minus 0.5 days, which may lead to a biased estimate. However, considering the small proportion [1,304 (0.4%)] and robust results of sensitivity analyses (Supplementary Table S3), the bias may not influence the results substantially. Third, almost 20% of the population was excluded at baseline, which may cause selection bias inevitably. However, we compared baseline characteristics between included and excluded participants, finding that the distribution of baseline characteristics was comparable between the two groups (data not shown). Furthermore, we conducted a multivariate imputation, and no substantial changes in results were found (data not shown).

      In summary, our study suggested that physical activity could reduce CMD incidence and further progression, albeit to different extents. Adults should engage in physical activity, meeting the WHO Guidelines as early as possible, especially those initially free of CMDs.

    • We wish to acknowledge the UK Biobank Resource under Application Number 69550 and also gratefully acknowledge all participants who provided data to the UK Biobank.

    • No conflicts of interest.

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