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Role of Muscular Strength on the Risk of Sudden Cardiac Death in Men

      To the Editor:
      The effect of cardiorespiratory fitness (CRF) on sudden cardiac death (SCD) has been summarized,
      • Jiménez-Pavón D.
      • Lavie C.J.
      • Blair S.N.
      The role of cardiorespiratory fitness on the risk of sudden cardiac death at the population level: a systematic review and meta-analysis of the available evidence.
      with the conclusion that the risk of SCD decreases by 14% to 22% per 1-metabolic equivalent task increase in CRF.
      • Jiménez-Pavón D.
      • Lavie C.J.
      • Blair S.N.
      The role of cardiorespiratory fitness on the risk of sudden cardiac death at the population level: a systematic review and meta-analysis of the available evidence.
      Recently, Mayo Clinic Proceedings has not only emphasized articles on CRF
      • Myers J.
      • Doom R.
      • King R.
      • et al.
      Association between cardiorespiratory fitness and health care costs: the Veterans Exercise Testing Study.
      • McAuley P.A.
      • Keteyian S.J.
      • Brawner C.A.
      • et al.
      Exercise capacity and the obesity paradox in heart failure: the FIT (Henry Ford Exercise Testing) Project.
      • Kokkinos P.
      • Myers J.
      • Franklin B.
      • Narayan P.
      • Lavie C.J.
      • Faselis C.
      Cardiorespiratory fitness and health outcomes: a call to standardize fitness categories.
      but also articles on resistance exercise and muscular strength (MusS).
      • Bakker E.A.
      • Lee D.C.
      • Sui X.
      • et al.
      Association of resistance exercise, independent of and combined with aerobic exercise, with the incidence of metabolic syndrome.
      • Bakker E.A.
      • Lee D.C.
      • Sui X.
      • et al.
      Association of resistance exercise with the incidence of hypercholesterolemia in men.
      • Wang Y.
      • Lee D.C.
      • Brellenthin A.G.
      • et al.
      Association of muscular strength and incidence of type 2 diabetes.
      However, there is no study of the effect of MusS on SCD, even though MusS was inversely and independently associated with all-cause mortality in healthy men.
      • Ruiz J.R.
      • Sui X.
      • Lobelo F.
      • et al.
      Association between muscular strength and mortality in men: prospective cohort study.
      Consequently, this report investigated the effect of MusS as a predictor of SCD, independent of potential risk factors, and explored the combined influence of MusS and CRF on the risk of SCD.
      This report is based on data from the Aerobics Center Longitudinal Study, a prospective observational investigation. For the present analysis, men 18 years or older with data on MusS and potential confounders (eg, medical history and lifestyle behaviors) as well as at least 1 year of mortality follow-up were included. Participants were predominantly white, well-educated, and belonged to the middle and upper socioeconomic strata. We could not include women because of the limited SCD cases (n=2).
      Muscular strength was assessed in the upper and lower body by using a standardized bench and leg press strength testing protocol as previously reported.
      • Ruiz J.R.
      • Sui X.
      • Lobelo F.
      • et al.
      Association between muscular strength and mortality in men: prospective cohort study.
      A composite strength score was computed by averaging together the body weight–adjusted then standardized values of bench and leg press. For SCD events, the National Death Index was the primary data source for mortality surveillance, augmented with death certificates.
      • Jiménez-Pavón D.
      • Lavie C.J.
      • Blair S.N.
      The role of cardiorespiratory fitness on the risk of sudden cardiac death at the population level: a systematic review and meta-analysis of the available evidence.
      Cox proportional hazards regression was used to compute hazard ratios (HRs; 95% CIs) of SCD for tertiles of MusS (models 1-3 in the Table).
      TableSample Characteristics and Association of MusS With the Risk of SCD
      CRF = cardiorespiratory fitness; CVD = cardiovascular disease; MET = metabolic equivalent task; MusS = muscular strength; SCD = sudden cardiac death.
      ,
      Data are presented as mean ± SD or as No. (percentage) unless indicated otherwise. Bold text indicates significant results.
      ,
      Data were analyzed using the chi-square tests (categorical variables) or F tests (continuous variables).
      VariableOverallTertiles of MusSP Value
      LowerMiddleUpper
      Sample characteristics
       No. of participants8116269627232697
       Age (y)42.0±9.742.5±9.642.1±9.741.4±9.8<.0001
       Body mass index (kg/m2)26.1±3.727.3±4.425.8±3.225.2±2.9<.0001
       Meeting aerobic physical activity guidelines
      ≥500 MET-minutes per week.
      3056 (38)840 (31)992 (36)1224 (45)<.0001
       Current smoking status
      Current smoking: yes or no.
      1315 (16)493 (18)464 (17)358 (13)<.0001
       Heavy alcohol drinking
      >14 drinks/wk.
      1991 (25)695 (26)705 (26)591 (22).0006
       Parental history of CVD
      Parental history of CVD: yes or no.
      2359 (29)804 (30)802 (29)753 (28).2641
       Abnormal electrocardiogram
      Abnormal electrocardiogram: yes or no from the resting or exercise electrocardiogram.
      459 (6)170 (6)153 (6)136 (5).1326
       Hypertension
      Hypertension: yes or no from self-report or measured blood pressure ≥140/90 mm Hg.
      2177 (27)848 (31)685 (26)644 (24)<.0001
       Diabetes
      Diabetes: yes or no from self-report, taking insulin, or measured glucose level ≥126 mg/dL (to convert to mmol/L, multiply by 0.0259).
      226 (3)106 (4)64 (2)56 (2)<.0001
       CRF data(MET)
      Only in the subsample with CRF data (n=7669).
      12.4±2.511.3±2.312.4±2.413.4±2.5<.0001
      Upper body strength
       kg72.0 (17.7)62.0 (12.7)70.3 (12.9)83.7 (19.3)<.0001
       kg/kg of body weight0.9 (0.2)0.7 (0.1)0.9 (0.1)1.1 (0.2)<.0001
      Lower body strength
       kg138.1 (27.6)126.2 (26.1)136.8 (23.7)151.2 (26.8)<.0001
       kg/kg of body weight1.7 (0.3)1.4 (0.2)1.7 (0.2)1.9 (0.3)<.0001
       Composite strength score8.6×10−6 (0.91)−0.81 (0.48)−0.05 (0.44)0.87 (0.79)<.0001
      Association of MusS with the risk of SCD
      VariableTertiles of MusSPer 1-SD increase
      Total muscular strength scores were standardized into z scores using the sample’s mean and SD of their standardized total strength (combined with body weight–adjusted leg and chest press) scores. The total muscular strength z scores had a mean of 0 and an SD of 1.
      LowerMiddleUpper
       No. of participants2696272326978116
       No. of SCD cases134623
       Hazard ratio (95% CI): model 1
      Adjusted for age.
      1.00 (reference)0.28 (0.09- 0.87)0.43 (0.16-1.14)0.57 (0.33-0.96)
       Hazard ratio (95% CI): model 2
      Adjusted for model 1 plus body mass index, meeting aerobic physical activity guidelines (≥500 MET-minutes per week), current smoking, and heavy alcohol drinking (>14 drinks/wk).
      1.00 (reference)0.31 (0.10-0.97)0.48 (0.17-1.32)0.61 (0.35-1.05)
       Hazard ratio (95% CI): model 3
      Adjusted for model 2 plus parental history of cardiovascular disease, abnormal electrocardiogram, hypertension, and diabetes (all yes or no).
      1.00 (reference)0.31 (0.10-0.96)0.52 (0.19-1.44)0.63 (0.36-1.11)
      a CRF = cardiorespiratory fitness; CVD = cardiovascular disease; MET = metabolic equivalent task; MusS = muscular strength; SCD = sudden cardiac death.
      b Data are presented as mean ± SD or as No. (percentage) unless indicated otherwise. Bold text indicates significant results.
      c Data were analyzed using the chi-square tests (categorical variables) or F tests (continuous variables).
      d ≥500 MET-minutes per week.
      e Current smoking: yes or no.
      f >14 drinks/wk.
      g Parental history of CVD: yes or no.
      h Abnormal electrocardiogram: yes or no from the resting or exercise electrocardiogram.
      i Hypertension: yes or no from self-report or measured blood pressure ≥140/90 mm Hg.
      j Diabetes: yes or no from self-report, taking insulin, or measured glucose level ≥126 mg/dL (to convert to mmol/L, multiply by 0.0259).
      k Only in the subsample with CRF data (n=7669).
      l Total muscular strength scores were standardized into z scores using the sample’s mean and SD of their standardized total strength (combined with body weight–adjusted leg and chest press) scores. The total muscular strength z scores had a mean of 0 and an SD of 1.
      m Adjusted for age.
      n Adjusted for model 1 plus body mass index, meeting aerobic physical activity guidelines (≥500 MET-minutes per week), current smoking, and heavy alcohol drinking (>14 drinks/wk).
      o Adjusted for model 2 plus parental history of cardiovascular disease, abnormal electrocardiogram, hypertension, and diabetes (all yes or no).
      A total of 8116 men were included, and 23 cases of SCD occurred over a mean follow-up of 18.4±2.8 years. Compared with the lower third of MusS, there was a 69% reduced risk of SCD in the middle third of MusS after adjusting for model 3 (Table). Although statistically not substantial, we also observed an approximately 50% reduced risk of mortality in the upper third of MusS in all models. In additional analyses, we further adjusted for CRF in a subsample of men with complete and valid CRF data (n=7669; 21 SCD cases) and found that there was a 58% reduced risk of SCD in the middle third of MusS, although no longer statistically significant (HR, 0.42; 95% CI, 0.13-1.36). Moreover, a 1-SD increase in MusS was associated with a 43% reduced risk of SCD in model 1.
      In the subsample with CRF data, men were dichotomized into weak (lower third of MusS) or strong (middle and upper thirds of MusS) and unfit (lower third of CRF) or fit (middle and upper thirds of CRF) groups for a joint analysis, as previously done.
      • Ruiz J.R.
      • Sui X.
      • Lobelo F.
      • et al.
      Association between muscular strength and mortality in men: prospective cohort study.
      Compared with the weak and unfit group as a reference, the HR (95% CI) for the unfit and strong, fit and weak, and fit and strong groups was 0.39 (0.10-1.50), 0.61 (0.17-2.26), and 0.28 (0.08-0.94), respectively, after adjusting for the full set of confounders in model 3, indicating a potential additive benefit of being fit combined with being strong.
      Muscular strength was associated with a reduced risk of SCD, independent of several risk factors, including aerobic physical activity. However, the results were attenuated and no longer significant when CRF was included in the model. It is not clear whether this is due to the confounding effects of CRF on the association or due to the reduced sample size and SCD cases. However, we noted that there was a 58% reduced risk of SCD in the middle third of MusS even after adjusting for CRF, although not significant. Moreover, the joint analysis indicated that being both fit and strong may provide the greatest benefit on preventing the risk of SCD significantly by 72% (0.28 [0.08-0.94]). To our knowledge, this is the first study to report the protective effect of MusS on SCD risk, independent of several risk factors, and the first to report the additional value of the combination of high MusS and CRF for the reduction in SCD risk.
      These findings offer new insights into the prevention of SCD through increasing MusS in addition to the previously documented protective benefits of CRF.
      • Jiménez-Pavón D.
      • Lavie C.J.
      • Blair S.N.
      The role of cardiorespiratory fitness on the risk of sudden cardiac death at the population level: a systematic review and meta-analysis of the available evidence.
      Moreover, this supports previous research indicating that both MusS and CRF predict all-cause mortality risk.
      • Ruiz J.R.
      • Sui X.
      • Lobelo F.
      • et al.
      Association between muscular strength and mortality in men: prospective cohort study.
      The apparent protective effect of MusS against the risk of SCD might be due to the direct effect of muscle strength, which is considered an index of muscle quality and function that is generally improved by resistance exercise. Resistance exercise is associated with better functional capacity, metabolic and inflammation profiles,
      • Williams M.A.
      • Haskell W.L.
      • Ades P.A.
      • et al.
      American Heart Association Council on Clinical CardiologyAmerican Heart Association Council on Nutrition, Physical Activity, and Metabolism
      Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity, and Metabolism.
      and recently with better survival.
      • Liu Y.
      • Lee D.C.
      • Li Y.
      • et al.
      Associations of resistance exercise with cardiovascular disease morbidity and mortality.
      In fact, the results of intervention studies indicate that resistance training enhances MusS and endurance, muscle mass, functional capacity, risk profile for cardiovascular disease, and quality of life,
      • Williams M.A.
      • Haskell W.L.
      • Ades P.A.
      • et al.
      American Heart Association Council on Clinical CardiologyAmerican Heart Association Council on Nutrition, Physical Activity, and Metabolism
      Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity, and Metabolism.
      which are well-known predictors of overall mortality.
      This study is limited by the small sample size and SCD cases, which may partially contribute to no significant result in the upper third of MusS. However, the reduction in SCD risk for those with moderate MusS or the combination of both high MusS and CRF was even higher (69% or 72%, respectively) than that previously found for CRF alone (44%-48% risk reduction) in a larger sample of the Aerobics Center Longitudinal Study cohort (n=59,611).
      • Jiménez-Pavón D.
      • Lavie C.J.
      • Blair S.N.
      The role of cardiorespiratory fitness on the risk of sudden cardiac death at the population level: a systematic review and meta-analysis of the available evidence.
      Further studies are needed to assess the combined effects of MusS and CRF on the prevention of SCD.

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