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Mortality associated with metabolic syndrome in people with COPD managed in primary care

Urvee Karsanji, Rachael A. Evans, Jennifer K. Quint, Kamlesh Khunti, Claire A. Lawson, Emily Petherick, Neil J. Greening, Sally J. Singh, Matthew Richardson, Michael C. Steiner
ERJ Open Research 2022 8: 00211-2022; DOI: 10.1183/23120541.00211-2022
Urvee Karsanji
1NIHR Leicester Biomedical Research Centre – Respiratory, Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
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  • ORCID record for Urvee Karsanji
Rachael A. Evans
1NIHR Leicester Biomedical Research Centre – Respiratory, Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
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  • ORCID record for Rachael A. Evans
Jennifer K. Quint
2National Heart and Lung Institute, Imperial College London, London, UK
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Kamlesh Khunti
3NIHR Applied Research Collaboration East Midlands, Diabetes Research Centre, University of Leicester, Leicester, UK
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Claire A. Lawson
3NIHR Applied Research Collaboration East Midlands, Diabetes Research Centre, University of Leicester, Leicester, UK
4Dept of Cardiovascular Sciences, University of Leicester, Leicester, UK
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Emily Petherick
5School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
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Neil J. Greening
1NIHR Leicester Biomedical Research Centre – Respiratory, Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
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Sally J. Singh
1NIHR Leicester Biomedical Research Centre – Respiratory, Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
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Matthew Richardson
1NIHR Leicester Biomedical Research Centre – Respiratory, Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
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Michael C. Steiner
1NIHR Leicester Biomedical Research Centre – Respiratory, Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
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  • For correspondence: ms346@leicester.ac.uk
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  • FIGURE 1
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    FIGURE 1

    Flowchart identifying the cohort of COPD patients used to apply the components of the metabolic syndrome (MetS) definition using complete case analysis for the components of MetS and disease predictors: Medical Research Council (MRC) score, forced expiratory volume in 1 s (FEV1) % predicted and body mass index (BMI). The variables FEV1 % predicted, BMI and MRC grade each had over 25% missingness, hence were excluded from the cohort and full-case analysis was used leaving a generous sample of n=40 806 patients. CPRD: Clinical Practice Research Datalink; HES: Hospital Episode Statistics; ONS: Office for National Statistics; IMD: Index of Multiple Deprivation.

  • FIGURE 2
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    FIGURE 2

    The association of the presence of metabolic syndrome (MetS) with all-cause mortality. KM: Kaplan–Meier.

  • FIGURE 3
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    FIGURE 3

    Kaplan–Meier (KM) survival curves showing survival probability by component of metabolic syndrome (MetS) definition: obesity, high-density lipoprotein (HDL) status, triglyceride status (TG), hypertension and type 2 (T2) diabetes mellitus.

Tables

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  • TABLE 1

    Baseline characteristics for the population defined by the presence of metabolic syndrome (MetS)

    AllMetSNon-MetS
    Subjects n40 806414136 665
    Sex
     Male22 165 (54.32)2421 (58.46)19 744 (53.85)
     Female18 641 (45.68)1720 (41.54)16 921 (46.15)
    Ethnicity
     Black196 (0.48)23 (0.56)173 (0.47)
     Mixed other216 (0.53)22 (0.53)194 (0.53)
     South Asian416 (1.02)70 (1.69)346 (0.94)
     Unknown1742 (4.27)55 (1.33)1687 (4.60)
     White38 236 (93.70)3971 (95.89)34 265 (93.45
    Age years, mean±sd68.69±10.7468.92±9.6068.66±10.87
     35–44675 (1.65)49 (1.18)626 (1.71)
     45–543659 (8.97)281 (6.79)3378 (9.21)
     55–649431 (23.11)973 (23.50)8458 (23.07)
     65–7414 228 (34.87)1597 (38.57)12 631 (34.45)
     75+12 813 (31.40)1241 (29.97)11 572 (31.56)
    BMI kg·m−2, mean±sd27.56±6.0234.10±5.6626.82±5.60
     Underweight (<18.5)1546 (3.79)6 (0.14)1540 (4.20)
     Normal (18.5–24.9)13 168 (32.27)169 (4.08)12 999 (35.45)
     Overweight (25–29.9)13 719 (33.62)474 (11.45)13 245 (36.12)
     Obese (30–39.9)10 929 (26.78)2926 (70.66)8003 (21.83)
     Severely obese (≥40)1444 (3.54)566 (13.67)878 (2.39)
    Smoking status
     Current smoker14 532 (35.61)1147 (27.70)13 385 (36.51)
     Nonsmoker/never4544 (11.14)501 (12.10)4043 (11.03)
     Ex-smoker21 011 (51.49)2448 (59.12)18 563 (50.63)
     Missing719 (1.76)45 (1.09)674 (1.84)
    Index of multiple deprivation
     1=least deprived6331 (15.51)559 (13.50)5772 (15.74)
     27581 (18.58)684 (16.52)6897 (18.81)
     37797 (19.11)771 (18.62)7026 (19.16)
     49152 (22.43)950 (22.94)8202 (22.37)
     5=most deprived9945 (24.37)1177 (28.42)8768 (23.91)
    FEV1 % predicted, mean±sd63.11±22.7664.25±20.5662.98±23.00
    Number of exacerbations in previous year
     026 773 (65.61)2678 (64.67)24 095 (65.72)
     19191 (22.52)912 (22.02)8279 (22.58)
     23005 (7.36)342 (8.26)2663 (7.26)
     31086 (2.66)118 (2.85)968 (2.64)
     4395 (0.97)51 (1.23)344 (0.94)
     5212 (0.52)26 (0.63)186 (0.51)
     689 (0.22)11 (0.27)78 (0.21)
     7+55 (0.13)3 (0.07)52 (0.14)
    MRC dyspnoea score
     1=least severe7928 (19.43)568 (13.72)7360 (20.07)
     216 688 (40.90)1458 (35.21)15 230 (41.54)
     310 161 (24.90)1191 (28.76)8970 (24.46)
     45173 (12.68)793 (19.15)4380 (11.95)
     5=most severe856 (2.10)131 (3.16)725 (1.98)
    GOLD, n (%)
     I8577 (21.02)837 (20.21)7740 (21.11)
     II19 776 (48.46)2248 (54.29)17 528 (47.81)
     III10 150 (24.87)935 (22.58)9215 (25.13)
     IV2303 (5.64)121 (2.92)2182 (5.95)
    Components of MetS definition
     Obesity (BMI at least 30)12 373 (30.32)3492 (84.33)8881 (24.22)
     Hypertension14 846 (36.38)3515 (84.88)11 331 (30.90)
     HDL (<40 mg·dL−1 (men); <50 mg·dL−1 (women))6231 (15.27)2862 (69.11)3369 (9.19)
     TG (>150 mg·dL−1)595 (1.46)418 (10.09)177 (0.48)
     T2DM6967 (17.07)3255 (78.60)3712 (10.12)
    Comorbidities
     Liver disease982 (2.41)196 (4.73)786 (2.14)
     Kidney disease5845 (14.32)1049 (25.33)4796 (13.08)
     Psychological disease4258 (10.43)554 (13.38)3704 (10.10)
     Frailty1514 (3.71)229 (5.53)1285 (3.50)
     Asthma16 315 (39.98)1886 (45.54)14 429 (39.35)
     CVD7416 (18.17)1415 (34.17)6001 (16.37)
     Musculoskeletal8972 (21.99)1316 (31.78)7656 (20.88)
     GERD3581 (8.78)471 (11.37)3110 (8.48)

    Categorical data presented as n (%) unless otherwise indicated. BMI: body mass index; FEV1: forced expiratory volume in 1 s; MRC: Medical Research Council; GOLD: Global Initiative for Chronic Obstructive Lung Disease; HDL: high-density lipoprotein; TG: triglyceride; T2DM: type 2 diabetes mellitus; CVD: cardiovascular disease; GERD: gastroesophageal reflux disorder.

    • TABLE 2

      Multiple associations using the odds ratio (OR) between disease and demographic variables and the presence of metabolic syndrome (MetS)

      VariableORp-value
      genderFemaleref.
      genderMale1.20<0.001
      age0.98<0.001
      ethnicityWhiteref.
      ethnicityBlack1.150.551
      ethnicityMixed_Other0.990.970
      ethnicitySouth Asian1.70<0.001
      ethnicityUnknown0.43<0.001
      smokingNonref.
      smokingEx1.050.337
      smokingCurrent0.68<0.001
      smokingMissing0.58<0.001
      imd1ref.
      imd21.000.947
      imd31.090.156
      imd41.150.137
      imd51.32<0.001
      fev1pp1.00<0.001
      n_exacs0.960.027
      mrc1ref.
      mrc21.21<0.001
      mrc31.57<0.001
      mrc42.02<0.001
      mrc51.97<0.001
      liver1.74<0.001
      kidney1.79<0.001
      psych1.150.006
      frail1.32<0.001
      asthma1.16<0.001
      cvd2.22<0.001
      mskel1.51<0.001
      gerd1.080.139

      Variables highlighted in bold are associated with the presence of MetS.

      • TABLE 3

        Hazard ratios (HRs) for all-cause mortality for the presence of metabolic syndrome and individual components

        VariableHR (95% CI)p-value
        mets1.19 (1.12–1.27)<0.001
        obese0.74 (0.71–0.78)<0.001
        hyp1.70 (1.63–1.77)<0.001
        lowhdl1.00 (0.95–1.06)0.885
        hightg0.83 (0.69–0.99)0.041
        diabetesT21.41 (1.34–1.48)<0.001

        Variables highlighted in bold are associated with 5-year all-cause mortality.

        • TABLE 4

          Multivariable hazard ratio (HR) model between adjustment variables and 5-year all-cause mortality

          VariableHR (95% CI)p-value
          mets=0ref-
          mets=11.06 (0.99–1.13)0.085
          genderFemaleref-
          genderMale1.33 (1.27–1.38)<0.001
          age1.07 (1.07–1.07)<0.001
          ethnicityWhiteref-
          ethnicityBlack0.63 (0.42–0.93)0.020
          ethnicityMixed_Other0.70 (0.55–0.90)0.005
          ethnicitySouth Asian0.99 (0.70–1.41)0.970
          ethnicityUnknown0.84 (0.72–0.97)0.020
          smokingNonref-
          smokingEx1.17 (1.10–1.26)<0.001
          smokingCurrent1.75 (1.62–1.89)<0.001
          smokingMissing1.16 (1.00–1.35)0.044
          imd1ref-
          imd21.05 (0.98–1.12)0.190
          imd31.06 (0.99–1.14)0.102
          imd41.05 (0.98–1.12)0.193
          imd51.13 (1.05–1.20)<0.001
          fev1pp0.99 (0.99–0.99)<0.001
          n_exacs1.08 (1.06–1.10)<0.001
          mrc1ref-
          mrc21.21 (1.12–1.29)<0.001
          mrc31.53 (1.42–1.64)<0.001
          mrc41.89 (1.75–2.04)<0.001
          mrc52.88 (2.57–3.22)<0.001
          liver1.53 (1.36–1.72)<0.001
          kidney1.25 (1.19–1.32)<0.001
          psych1.41 (1.32–1.51)<0.001
          frail1.26 (1.15–1.38)<0.001
          asthma0.93 (0.89–0.97)<0.001
          cvd1.44 (1.37–1.51)<0.001
          mskel1.02 (0.98–1.07)0.350
          gerd0.99 (0.91–1.06)0.700

          Variables highlighted in bold are associated with 5-year all-cause mortality.

          • TABLE 5

            Stratified multivariable survival model on 5-year all-cause mortality by the presence of metabolic syndrome

            Adjusted forVariableHR (95% CI)p-value
            Demographicsmets=11.17 (1.10–125)<0.001
            IMDmets=11.19 (1.12–1.27)<0.001
            COPD severitymets=11.13 (1.02–1.25)0.021
            Comorbiditiesmets=10.95 (0.89–1.01)0.100

            HR: hazard ratio; IMD: Index of Multiple Deprivation. Variables highlighted in bold are associated with 5-year all-cause mortality.

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              Supplementary material 00211-2022.SUPPLEMENT

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            Mortality associated with metabolic syndrome in people with COPD managed in primary care
            Urvee Karsanji, Rachael A. Evans, Jennifer K. Quint, Kamlesh Khunti, Claire A. Lawson, Emily Petherick, Neil J. Greening, Sally J. Singh, Matthew Richardson, Michael C. Steiner
            ERJ Open Research Oct 2022, 8 (4) 00211-2022; DOI: 10.1183/23120541.00211-2022

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            Mortality associated with metabolic syndrome in people with COPD managed in primary care
            Urvee Karsanji, Rachael A. Evans, Jennifer K. Quint, Kamlesh Khunti, Claire A. Lawson, Emily Petherick, Neil J. Greening, Sally J. Singh, Matthew Richardson, Michael C. Steiner
            ERJ Open Research Oct 2022, 8 (4) 00211-2022; DOI: 10.1183/23120541.00211-2022
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