J. Exp. Biomed. Sci. 2011, 17(4): 305~311 Association of Metabolic Syndrome with Exercise Capacity and Heart Rate Recovery after Treadmill Exercise Test Kyung-A Shin Department of Laboratory Medicine Bundang Jesaeng Hospital, Sungnam-si, Gyeonggi-do 463-774, Korea Heart rate recovery (HRR) immediately after a treadmill exercise test is a function of vagal reactivation. A delayed heart rate recovery is associated with an increased risk for overall cardiovascular mortality. The purpose of this study is to find out if metabolic syndrome is associated with autonomic nerve function and exercise capacity in healthy adults. We measured the treadmill exercise capacity (METs) and heart rate recovery in 119 subjects through a medical checkup at J General Hospital. The metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. The value for the HRR was defined as the difference between the heart rate obtained during the peak exercise and the heart rate obtained at first minute during the recovery period. The subjects with the metabolic syndrome had significantly lower exercise duration (9.6±1.5 vs 8.7±1.4), METs (11.6±1.7 vs 10.4±2.5), and HRR (37.5±14.3 vs 27.1±8.9). The waist circumference in subjects with the metabolic syndrome was more strongly correlated with HRR (r=-.517, P<.001) than in normal subjects. Furthermore, delayed HRR was associated with high resting heart rate and increased waist circumference (P=.032, P<.001, respectively). In conclusion, delayed HRR during the first minute after a treadmill exercise test was associated with the metabolic syndrome risk factors. Delayed HRR was also associated with high resting heart rate and increased waist circumference. Key Words: Metabolic syndrome, Exercise capacity, Heart rate recovery, Vagal reactivation 서 운동중심박수증가는부교감신경의활성도감소와동방결절에대한교감신경의활성화가균형을이룬것이며 (Arai et al., 1989), 자율신경계불균형을측정하는데유용한운동후심박수회복 (heart rate recovery: HRR) 은미주신경재활성 (vagal reactivation) 을반영하는지표이다 (Cole et al., 1999). 심박수회복의지연은미주신경계활성의감소나과도한교감신경계항진을의미하며 (Schwartz et al., 1992; Imai et al., 1994), 이러한운동부하검사직후나타나는느린심박수회복반응은허혈성심장질환자, 당뇨환자, 일반성인을대상으로한연구에서전체사망률과심혈관 * 접수일 : 2011년 8월 22일 / 수정일 : 2011년 12월 26일채택일 : 2011년 12월 27일 교신저자 : 신경아, ( 우 ) 463-050 경기도성남시분당구서현동 255-2, 분당제생병원진단검사의학과 Tel: 010-2759-8672, Fax: 031-779-0257 e-mail: mobitz2@daum.net 론 질환에의한사망률의독립적인예측인자로제시되고있다 (Cole et al., 1999; Cheng et al., 2003; Vivekananthan et al., 2003). 심박수회복은대상자의특성에따라서도다양한반응을보이는데운동선수의경우심박수회복은빠르게이루어지지만심부전환자는느리며, 부교감신경억제제인아트로핀사용에의해서심박수회복은둔화된다 (Imai et al., 1994; Cole et al., 1999). Spies 등 (2005) 은관상동맥질환자의대사증후군과심박수회복및운동능력간의관련성을평가하였으며, 대사증후군은관상동맥질환자에서낮은심박수회복및운동능력과관련이있음을보고하였다. 또한비만은자율신경계불균형을일으키는요인으로인체측정학적변인중체질량지수와허리둘레는심박수회복과독립적인관련이있는것으로보고되었다 (Dimkpa and Oji, 2009). 심박수회복은운동중도달한최대심박수에서회복기시간대의심박수를뺀수치로규정되며, 선행연구 (Savonen et al., 2011) 에서심박수회복의기준은자전거에르고미터를이용하여최대운동부하검사후회복기 - 305 -
2분대심박수를최대심박수에서뺀값으로정의하였다. 또한 Cole 등 (1999) 에따르면트레드밀운동부하검사를통해최대심박수에서운동후회복기 1분대심박수를뺀수치로정의하고있으나, 이와같은다양한규정의차이에도심박수회복은전체사망률의독립적인예측인자로보고된다. 이와같이운동정지후심박수회복의진단적가치에대해서는많이알려져있지만그기전은아직명확하지않으며, 국내에서는대사증후군에서의운동능력및자율신경기능과의관련성에관한연구는부족한실정이다. 따라서본연구에서는대사증후군진단군과대사증후군위험요인이없는군으로분류하여운동능력및심박수회복반응의차이를비교평가하고, 심박수회복에영향을미치는위험요인을알아보고자하였다. 재료및방법피험자이연구의대상자는 2008년 7월부터 2011년 7월까지경기지역 J 종합병원에서심장특화건강검진을통해운동부하검사를실시한 332명중대사증후군위험요인이없는군과대사증후군진단군으로판정된 30세이상 119 명 ( 남성 75명, 여성 44명 ) 을연구대상으로하였다. 대사증후군진단기준은 Executive Summary of The Third Report of The National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) 에서제시한 1) 혈압 130/85 mmhg, 2) 공복혈당 110 mg/dl, 3) high density lipoprotein (HDL) 콜레스테롤은남성 <40 mg/dl, 여성 <50 mg/dl, 4) 중성지방 (triglyceride) 150 mg/dl, 5) 허리둘레남성 >102 cm, 여성 >88 cm이며, 위의 5가지항목중위험요인이없는군을정상군, 3개이상항목에만족하는경우대사증후군진단군으로정의하였다 (NCEP- ATP III, 2001). 대사증후군기준중허리둘레는서양인의기준으로동양인에부적합하다고판단되어아시아태평양지역의복부비만기준 (Asia-Pacific Criteria: APC) 에따라남성 >90 cm, 여성 >80 cm를적용하였다 (WHO, 2000). 고혈압, 당뇨병의병력이있는경우는대사증후군해당항목기준에속하는것으로간주하였다. 연구대상자중뇌, 심혈관질환자로지질대사에영향을미치는지질강하제, 심박수에영향을주는베타차단제와같은약물을복용하는경우대상에서제외하였으며, 과거병력, 약물복용여부는 설문을통해파악하였다. 이연구는 J 종합병원윤리심의위원회 (Institutional Review Board: IRB) 승인을받았으며, 연구목적과방법에대해피험자들에게사전에설명을하고서면동의서를받아실시하였다. 점증적운동부하검사운동부하검사는트레드밀 (Medtrack ST 55, Quinton Instrument Co., U.S.A) 을이용하여 3분마다속도와경사도를증가시키는 Bruce 프로토콜에따라검사중흉통, 어지러움, 심한호흡곤란같은증상이있거나, 위험한심전도와혈압반응에근거하여검사를종료하는증상제한적운동부하검사 (symptom limited exercise test) 를시행하였다. 운동부하검사중최고혈압과심박수는최대운동시혈압과심박수를측정하였으며, 회복시프로토콜은운동직후경사도 0% 에서 30~40초간가볍게걷다가트레드밀이완전히멈춘후침대에누워 1분, 3분, 5분간심전도, 혈압, 심박수를측정하였다. 운동부하검사직후심박수회복 (heart rate recovery: HRR) 반응은운동중도달한최대심박수에서회복기 1분대의심박수를뺀값으로하였다 (Cole et al., 1999). 또한운동능력을나타내는대사당량 (metabolic equivalents: METs) 은다음공식을이용하여추정하였다. (Speed 0.1) + (Grade/100 1.8 Speed) + 3.5 METs = 3.5 심박변동성지수 (chronotropic index: CI) 는 ( 도달한최대심박수 - 안정시심박수 ) / ( 최대예측심박수 - 안정시심박수 ) 로계산하였으며, 최대예측심박수 (predicted maximal heart rate) 는 220 - 나이로계산하였다 (Fletcher et al., 2001). 신체계측및체성분분석혈압은수은혈압계를이용하여 10분간안정상태에서측정하였으며, 생체전기저항분석법 (Bio-electrical impedance analyzer) 을이용한 Inbody 4.0 (Biospace Co., Seoul, Korea) 을사용하여공복상태에서신장, 체중, 근육량과체지방량을계측하였다. 체질량지수는체중 (kg) / 키 (m 2 ) 의공식으로구하였으며, 허리둘레는직립자세에서숨을내쉰상태로허리가완전히노출되게한후최하위늑골하 - 306 -
Variable 부와골반장골능의중간부위를측정하였다. 혈액검사 Table 1. The clinical characteristics of the subjects Non-MS (n=75) MS (n=44) Age (years) 49.5±6.5 51.8±7.5 Female (%) 31 (41.3%) 13 (29.5%) Height (cm) 164.6±8.4 166.6±8.3 Weight (kg) 61.4±9.7 77.4±12.8 *** BMI (kg/m 2 ) 22.6±2.6 27.7±3.5 *** Muscle mass (kg) 43.4±7.9 50.4±8.9 *** Body fat mass (kg) 14.2±4.2 22.7±6.3 *** Waist circumference (cm) 76.1±6.9 90.4±8.6 *** Hip circumference (cm) 91.4±4.9 99.5±7.8 *** Systolic BP 104.0±12.1 125.7±19.2 *** Diastolic BP 67.1±9.0 91.5±13.2 *** Homocysteine (μmol/l) 11.0±3.7 12.5±4.0 * Insulin (μu/ml) 3.7±2.6 8.4±4.9 *** HbA1c (%) 5.5±0.3 6.3±1.0 *** Glucose (mg/dl) 88.3±7.9 111.6±31.6 *** HDL-cholesterol (mg/dl) 61.2±13.2 42.7±9.2 *** LDL-cholesterol (mg/dl) 125.2±29.3 119.3±30.5 Total cholesterol (mg/dl) 200.9±31.1 191.2±31.3 Triglyceride (mg/dl) 96.5±34.8 205.4±98.9 *** Uric acid (mg/dl) 5.1±1.4 6.0±1.4 ** CRP (mg/dl) 0.19±0.48 0.35±0.90 Previous diagnosis Hypertension (%) 0 23 (52.3%) Diabetes mellitus (%) 0 2 (4.5%) Values are Mean ± SD. ***, P<.001; **, P<.01; *, P<.05. Abbreviation: MS, metabolic syndrome; n, number of the subjects; BMI, body mass index; BP, blood pressure; HbA1c, hemoglobin A1c; HDL, high density lipoprotein; LDL, low density lipoprotein; CRP, C-reactive protein. 혈액분석은 8시간이상금식후아침에채혈을실시하였다. TBA-200FR NEO (Toshiba, Japan) 를이용하여 Homocysteine, high sensitivity C-reactive protein (hs-crp), HDL 콜레스테롤, low density lipoprotein (LDL) 콜레스테롤, 총콜레스테롤, 중성지방, 공복혈당, 요산 (Uric acid) 을측정하였으며, 당화혈색소 (hemoglobin A1c) 는 Variant II (Bio Rad, U.S.A) 를이용하여 high performance liquid chro- matography (HPLC) 법으로측정하였다. Insulin은 Modular analytics E-170 (Roche, U.S.A) 으로측정하였다. 자료처리방법이연구의모든자료는윈도우용 SPSS 12.0 통계프로그램 (SPSS Inc, Chicago, IL, U.S.A) 을이용하여기술통계치 (Mean ± SD) 를산출하였다. 대사증후군유무에따른운동능력및심박수회복의차이를검증하기위해 independent sample t-test를실시하였으며, 대사증후군위험요인과심박수회복간의관련성을알아보기위해 Pearson 의정률상관분석을적용하였다. 또한범주형변인의분석은 χ 2 검정을사용하였으며, 대사증후군위험요인이심박수회복반응에미치는영향을알아보기위해성별을보정한후다중회귀분석 (multiple linear regression) 을실시하였다. 통계적유의수준은 P<.05로하였다. 결과연구대상자의특성본연구에참여한대상자의특성은 Table 1에나타난바와같이, 신체구성을나타내는체중, 체질량지수, 근육량, 체지방량, 허리둘레와엉덩이둘레는정상군과비교해대사증후군진단군에서높은것으로나타났다. 또한수축기와이완기혈압은대사증후군진단군에서유의하게높게나타났다 ( 각각 P<.001). 혈액학적변인으로 homocysteine, insulin, HbA1c, 공복혈당, 중성지방, 요산은정상군에비해대사증후군진단군에서유의하게높게나타났으며, high density lipoprotein (HDL) 콜레스테롤은낮게나타났다. 또한대사증후군진단군에서이전에고혈압과당뇨병진단을받은경우는각각 52.3% 와 4.5% 로나타났다. 운동부하검사중운동능력및혈역학적요인 Table 2에서보는바와같이, 안정시심박수 (P=.005), 안정시수축기및이완기혈압은정상군에비해대사증후군진단군에서높게나타났으며 ( 각각 P<.001), 안정시심근산소소비량또한대사증후군진단군에서높은것으로나타났다 (P<.001). 최대운동시심박수, 최대수축기와이완기혈압은대사증후군진단군에서높게나타났으며 ( 각각 P<.001), 또한최대심근산소소비량은대사증후군진단군에서높게나타났다 (P=.014). - 307 -
Table 2. Exercise capacity and haemodynamic parameters during exercise treadmill test Variable Non-MS (n=75) MS (n=44) Resting HR (beats/min) 59.8±7.9 65.2±10.8 ** Resting systolic BP 110.7±14.6 126.8±14.9 *** Resting diastolic BP 68.4±10.0 81.1±12.1 *** Resting RPP 6625.6±1303.7 8301.2±1919.1 *** Maximum HR (beats/min) 161.0±10.7 152.3±14.1 *** Maximum systolic BP 156.2±19.1 178.1±22.4 *** Maximum diastolic BP 75.7±9.9 87.0±12.5 *** Maximum RPP 25211.7±3949.7 27239.3±4845.8 * Exercise duration (min) 9.6±1.5 8.7±1.4 ** Exercise capacity (METs) 11.6±1.7 10.4±2.5 *** HRR (beats/min) 37.5±14.3 27.1±8.9 *** CI 0.91±0.07 0.84±0.10 *** Table 3. Correlation between heart rate recovery and exercise capacity or metabolic risk factors Variable Coefficient P value BMI (kg/m 2 ) -.384 <.001 *** Systolic BP -.287.002 ** Diastolic BP -.269.003 ** Glucose (mg/dl) -.244.008 ** Total cholesterol (mg/dl).016.861 HDL-cholesterol (mg/dl).396 <.001 *** LDL-cholesterol (mg/dl) -.079.395 Triglyceride (mg/dl) -.284.002 ** Exercise duration (min).064.491 Exercise capacity (METs).059.524 Resting HR (beats/min) -.298.001 ** CI.189.040 * ***, P<.001; **, P<.01; *,P<.05. Abbreviation: HRR, heart rate recovery; BMI, body mass index; BP, blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; METs, metabolic equivalents; CI, chronotropic index. Values are Mean ± SD. ***, P<.001; **, P<.01; *,P<.05. Abbreviation: HR, heart rate; RPP, rate pressure product; METs, metabolic equivalents; HRR, heart rate recovery; CI, chronotropic index. 운동지속시간 (P=.005) 과운동능력을나타내는 METs, 심박수회복 ( 각각 P<.001) 은정상군에비해대사증후군진단군에서유의하게낮게나타났으며, 심박변동성지수또한대사증후군진단군에서낮게나타났다 (P<.001). 심박수회복과운동능력및대사증후군위험요인간의관련성 Table 3에서보는바와같이, 체질량지수, 수축기와이완기혈압, 공복혈당, 중성지방, 안정시심박수는심박수회복과역상관관계 (negative correlation) 를나타낸반면, HDL 콜레스테롤, 심박변동성지수는정상관관계 (positive correlation) 를보였다. 특히허리둘레가심박수회복과가장높은상관성을보이는것으로나타났다 (r= -.517, P<.001) (Fig. 1). 그러나운동지속시간및 METs 와심박수회복간에는관련이없는것으로나타났다. 대사증후군위험요인이심박수회복에미치는영향대사증후군위험요인을독립변인으로하고심박수회복을종속변인으로하여성별을보정한후다중회귀분석을시행한결과대사증후군위험요인중허리둘레가증가할수록심박수회복이감소하는것으로나타났다 (R 2 Fig. 1. Correlation with heart rate recovery (HRR) and waist circumference. =.349, F=4.210, P<.001). 또한안정시심박수가증가할수록심박수회복이감소하는것으로나타났다 (R 2 =.349, F=4.210, P=.032) (Table 4). 고 심박수회복 (heart rate recovery: HRR) 은심장자율신경계활성의지표로써운동부하검사직후심박수회복이늦을수록미주신경활성의저하를의미한다 (Cole et al., 1999). 또한늦은심박수회복은인슐린저항성, 염증지표의상승, 죽상경화증 (atherosclerosis), 혈관내피기능장애 찰 - 308 -
Table 4. Multiple linear regression between heart rate recovery and metabolic risk factors Variable β P-value BMI (kg/m 2 ).225.114 Waist circumference (cm) -.623 <.001 *** Systolic BP -.097.616 Diastolic BP.098.605 Glucose (mg/dl).112.298 Total cholesterol (mg/dl).067.883 HDL-cholesterol (mg/dl).119.587 LDL-cholesterol (mg/dl) -.130.770 Triglyceride (mg/dl) -.038.817 Exercise duration (min) -.005.974 Exercise capacity (METs) -.013.930 Resting HR (beats/min) -.206.032 * CI.064.445 R 2 (adj. R 2 ) =.349 (.266) R 2, coefficient of determination; ***, P<.001; *,P<.05. Abbreviation: HRR, heart rate recovery; BMI, body mass index; BP, blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; METs, metabolic equivalents; CI, chronotropic index. Adjusted for sex. 와관련이있다 (Lind and Andrén, 2002; Huang et al., 2004; Jae et al., 2007; Jae et al., 2008). 대사증후군위험요인의수가증가할수록심박수회복의지연을보이며 (Sung et al., 2006), 75세이상여성노인을대상으로대사증후군위험요인과심박수회복간에는관련이있는것으로보고된다 (Nilsson et al., 2007). 본연구결과에서는안정시와최대운동시심박수, 혈압은정상군에비해대사증후군진단군에서높게나타났으며, 운동지속시간과 METs (metabolic equivalents), 심박수회복은대사증후군진단군에서낮게나타났다. 이러한결과는대사증후군진단군에서낮은심박수회복과높은안정시심박수를보이며 (Sung et al., 2006), 심박수회복과운동능력은대사증후군진단군에서낮게나타났다는연구결과 (Deniz et al., 2007) 와일치한다. 또한안정시심박수의증가는교감신경활성의증가및높은혈압과관련이있으며, 심혈관사건증가의예측인자이다 (Deniz et al., 2007). 그러나이러한연구는대사증후군진단기준중복부비만을체질량지수로대체했으며, 심박수회복의진단기준으로회복기 3분대심박수를적용한제한점을가지고있다 (Sung et al., 2006). 대사증후군에서심박수회복의감소는낮은운동능력 과관련이있으며, 심혈관질환을예측하는데이용될수있다고제시된다 (Cole et al., 1999). 그러나또다른연구에서는최대산소섭취량은심박수회복과관련이없는것으로보고된다 (Sung et al., 2006). 본연구에서는심박수회복과운동지속시간및 METs 간에는관련이없는것으로나타났다. 이러한결과는운동능력을측정하는데있어서직접적으로산소섭취량 (VO 2 max) 을측정한것이아니라간접적으로추정한 METs 로운동능력을측정했기때문으로사료되며, 산소섭취량으로운동능력을측정한대규모연구가필요하리라생각된다. 건강한성인에서운동중낮은심박변동지수 (chronotropic index: CI) 는심혈관질환에의한사망률의강력한예측인자이다 (Savonen et al., 2006). 또한심근산소소비량 (rate pressure product: RPP) 은심박수, 수축력과심근벽의긴장 (wall tension) 이중요한결정요인으로써, 심도자술에의해직접적으로측정하는것이정확하나측정의어려움때문에심박수와수축기혈압의곱 (rate pressure product) 을이용하여간접적으로추정하는방법이주로이용된다 (Jorgensen et al., 1977). 이연구에서는대사증후군진단군에서낮은심박변동지수를보이고있으며, 안정시와최대운동시심근산소소비량이높게나타났다. 또한심박수와수축기혈압이대사증후군진단군에서높게나타나높은안정시심근산소소비량을보였으며, 높은혈압반응으로인해최대운동시심근산소소비량이높게나타난원인으로작용하였다. 운동증가와함께심박수및혈압의증가로인해심근산소소비량은증가하는데, 운동중과도한혈압의상승은심근경색과같은심혈관질환이동반되었을경우심근허혈을유발할수있는요인으로작용한다 (Kim and Shin, 2007). 그러므로대사증후군진단군에서의낮은심박변동지수와높은심근산소소비량은대사증후군이심혈관질환증가와관련이있다는연구에부합하는결과라할수있다 (Isomaa et al., 2001). 비만지표와운동후심박수회복간에독립적인관련이있으며, 특히중성지방과허리둘레의증가가대사증후군환자에서심박수회복과유의한관련성이있는것으로보고된다 (Dimkpa and Oji, 2009). 본연구결과, 허리둘레가심박수회복과가장높은관련성을보이며, 안정시심박수와허리둘레는심박수회복에영향을미치는위험요인으로나타났다. 그러나대사증후군진단군에서다이어트에의한체중감소, 운동, 베타 - 309 -
차단제및스타틴과같은약물복용이자율신경기능에긍정적인영향을미쳐심박수회복을개선시키는것으로나타났다 (Katircibasi et al., 2005; Deniz et al., 2007). 이러한결과를통해운동에의한체중감소는대사증후군위험요인에긍정적인영향을미치며, 대사증후군위험요인의감소는운동능력과심박수회복의향상에도영향을미칠것으로생각된다. 본연구의제한점으로는규칙적인운동수행유무는배제되었으며, 성별에따른운동능력과심박수회복의차이는규명하지못하였다. 결론적으로대사증후군위험요인은미주신경재활성지표인심박수회복의저하와관련이있으며, 허리둘레와안정시심박수는심박수회복에영향을미치는위험요인으로나타났다. REFERENCES Arai Y, Saul JP, Albrecht P, Hartley LH, Lilly LS, Cohen RJ, Colucci WS. Modulation of cardiac autonomic activity during and immediately after exercise. Am J Physiol. 1989. 256(1 Pt 2): H132-141. Cheng YJ, Lauer MS, Earnest CP, Church TS, Kampert JB, Gibbons LW, Blair SN. Heart rate recovery following maximal exercise testing as a predictor of cardiovascular disease and all-cause mortality in men with diabetes. Diabetes Care 2003. 26: 2052-2057. Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med. 1999. 341: 1351-1357. Deniz F, Katircibasi MT, Pamukcu B, Binici S, Sanisoglu SY. Association of metabolic syndrome with impaired heart rate recovery and low exercise capacity in young male adults. Clin Endocrinol (Oxf). 2007. 66: 218-223. Dimkpa U, Oji JO. Association of heart rate recovery after exercise with indices of obesity in healthy, non-obese adults. Eur J Appl Physiol. 2009. 108: 695-699. Expert panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001. 285: 2486-2497. Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Piña IL, Rodney R, Simons- Morton DA, Williams MA, Bazzarre T. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation 2001. 104: 1694-1740. Huang PH, Leu HB, Chen JW, Cheng CM, Huang CY, Tuan TC, Ding PY, Lin SJ. Usefulness of attenuated heart rate recovery immediately after exercise to predict endothelial dysfunction in patients with suspected coronary artery disease. Am J Cardiol. 2004. 93: 10-13. Imai K, Sato N, Hori M, Kusuoka H, Ozaki H, Yokoyama H. Vagally mediated heart rate recovery after exercise is accelerated in athletes but blunted in patient with chronic heart failure. J Am Coll Cardiol. 1994. 24: 1529-1535. Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001. 24: 683-689. Jae SY, Ahn ES, Heffernan KS, Woods JA, Lee MK, Park WH, Fernhall B. Relation of heart rate recovery after exercise to C-reactive protein and white blood cell count. Am J Cardiol. 2007. 99: 707-710. Jae SY, Carnethon MR, Heffernan KS, Choi YH, Lee MK, Park WH, Fernhall B. Slow heart rate recovery after exercise is associated with carotid atherosclerosis. Atherosclerosis 2008. 196: 256-261. Jorgensen CR, Gobel FL, Taylor HL, Wang Y. Myocardial blood flow and oxygen consumption during exercise. Ann N Y Acad Sci. 1977. 301: 213-223. Katircibasi MT, Canatar T, Kocum HT, Erol T, Tekin G, Demircan S, Tekin A, Sezgin AT, Baltali M, Muderrisoglu H. Decreased heart rate recovery in patients with heart failure: effect of fluvastatin therapy. Int Heart J. 2005. 46: 845-854. Kim YJ, Shin YO. Effects of aerobic exercise on cardiopulmonaryrelated factors in exercise-induced hypertension patients. Korean Society of Exercise Physiology 2007. 16: 131-140. Lind L, Andrén B. Heart rate recovery after exercise is related to the insulin resistance syndrome and heart rate variability in elderly men. Am Heart J. 2002. 144: 666-672. Nilsson G, Hedberg P, Jonason T, Lönnberg I, Ohrvik J. Heart rate recovery is more strongly associated with the metabolic syndrome, waist circumference, and insulin sensitivity in women than in men among the elderly in the general population. Am Heart J. 2007. 154: 460-467. Savonen KP, Lakka TA, Laukkanen JA, Halonen PM, Rauramaa - 310 -
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