원저 Korean Circulation J 2004;34(2):142-150 연령증가에따른혈압요소들의좌심실비대및관동맥질환과의관련성 고려대학교의과대학내과학교실 박재석 박창규 박미영 박재형 김용현 나진오 신성희 서순용홍순준 박성미 임홍의 김응주 서홍석 오동주 노영무 Relation of Blood Pressure Components to Left Ventricular Hypertrophy and Coronary Heart Disease with Aging Jae-Suk Park, MD, Chang-Gyu Park, MD, Mi-Young Park, MD, Jae-Hyoung Park, MD, Yong-Hyun Kim, MD, Jin-Oh Na, MD, Sung-Hee Shin, MD, Soon-Yong Suh, MD, Soon-Jun Hong, MD, Sung-Mi Park, MD, Hong-Euy Lim, MD, Eung-Joo Kim, MD, Hong-Seok Seo, MD, Dong-Joo Oh, MD and Young-Moo Ro, MD Department of Internal Medicine, Korea University Medical College, Seoul, Korea ABSTRACT Background and Objectives:There is still uncertainty regarding the relative importance of systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) in predicting the risk of cardiovascular disease. The relative importance of the BP components, as markers of left ventricular hypertrophy (LVH) and coronary artery disease (CAD), were examined in relation to age. Subjects and Methods:In 257 subjects receiving no antihypertensive medication, LVH was determined using the M-mode echocardiography when left ventricular mass index (LVMI) was 129 g/m 2 in men or 118 g/m 2 in women. In a further 265 subjects, CAD was determined using the coronary angiography when stenosis of the coronary arterial diameter was 70%. The most important BP component was determined using a logistic regression analysis. Results:With respect to LVH, in the group <50 years of age, odds ratios (ORs) per 10 mmhg increment in BP were 2.47 (p<0.01), 1.77 (p<0.01), 1.30 (p>0.10) for DBP, SBP and PP respectively. In the group 50 to 59 years of age, ORs were 1.65, 1.35, 1.36 (all p<0.05) for DBP, SBP and PP respectively. In the group 60 years of age, ORs were 1.56 (p<0.05), 1.67, 2.17 (both p<0.01) for DBP, SBP and PP respectively. With respect to CAD, in all age group, ORs were 0.93 (p>0.10), 1.07 (p>0.10), 1.21 (p<0.05) for DBP, SBP and PP respectively. In the group 60 years of age, no BP component had a statistical significance. Conclusion:With increasing age, there was a gradual shift from DBP to SBP and then to PP as the marker with the greatest relation to LVH. In all age group, PP was the strongest marker of CAD. (Korean Circulation J 2004;34 (2):142-150) KEY WORDS:Blood pressure;pulse pressure;left ventricular hypertrophy;coronary artery disease. 논문접수일 :2003 년 8 월 7 일수정논문접수일 :2003 년 9 월 16 일심사완료일 :2003 년 9 월 29 일교신저자 : 박창규, 152-703 서울구로구구로동길 98 번지고려대학교의과대학구로병원내과학교실전화 :(02) 818-6114 전송 :(02) 866-1643 E-mail:parkcg@kumc.or.kr 142
서 론 대상및방법 고혈압이심혈관질환의위험인자라고잘알려져있지만, 혈압요소중어느것이가장중요한지에대해서는아직명확하지않다. 과거에는확장기혈압이심혈관질환의위험을가장잘대변한다고생각되어졌다. 그러나, 1971년 Kannel 등은초기 Framingham 연구에서연령이증가할수록관동맥질환의예측인자로서확장기혈압의중요성이감소하면서수축기혈압의중요성이증가한다고발표하였고, 1) 이후여러연구에서노인에서수축기혈압을같이치료할때확장기혈압만을기준으로했을때보다심장병이 25~27% 정도감소하여 2) 이후에나온고혈압의진단과치료지침은수축기혈압과확장기혈압에의한심혈관질환의위험도를정의하였다. 최근에는 1999년 Framingham 연구와고령의일반인을대상으로한여러연구에서수축기혈압이증가하면서동시에확장기혈압이감소할때관동맥질환이더증가한다고하여맥압의예후적중요성이대두되었다. 3-5) 맥압은혈압이정상인사람, 6)7) 고혈압, 8)9) 심근경색, 10) 만성신부전환자 11) 에서심혈관질환의이환과사망에독립된예측인자라는보고가증가하고있다. 또한맥압은고혈압이나신부전환자에서좌심실비대의정도에도독립적인위험인자라고보고되었으며, 7)12-14) 수축기고혈압을가진노인에서맥압의증가는뇌졸중의이환과사망에도독립적으로관련되어있다고한다. 15) 2001년전체연령을대상으로한 Framingham 연구에서는관동맥질환의예측인자로서의중요성이연령이증가할수록확장기혈압에서수축기혈압으로그리고다시맥압으로이동한다고보고하였다. 6)16) 하지만대부분의연구들은추적관찰을통해혈압요소와향후심혈관질환의이환과의관계를조사하여혈압측정당시의관련성을알수없었고, 단지병력, 문진등역학적방법에의존하였을뿐실제로심초음파에의한좌심실비대나관동맥조영술에의한허혈성심질환을진단하여혈압요소와의관계를조사한연구는없었다. 따라서, 이번연구에서는수축기혈압, 확장기혈압, 맥압과혈압측정당시에심초음파로측정한좌심실비대및관동맥조영술로평가한관동맥질환사이의관련성을알아보고, 나아가이들혈압요소가운데어느것이심혈관질환의위험도를가장잘대변하는지알아보고자하였다. 대상심초음파를이용한연구방법에서는혈압이정상이거나고혈압환자중항고혈압약을최근 4주이상복용하지않은 257 명을대상으로하였고, 관동맥조영술을이용한연구방법에서는역시항고혈압약을복용한적이없는또다른 265 명을대상으로하였다. 두가지연구방법모두에서혈압요소에영향을미칠수있는요인으로이전에관상동맥중재술을시행한경우, 좌심실구혈율 50% 미만, 중등도이상의판막질환, 심방세동및맥박수 100 회이상인경우는연구대상에서제외하였다. 혈압의측정은심초음파나관동맥조영술을시행하기전에외래에서 10분이상앉은자세에서안정을취한후수은혈압계로 2회측정하여평균값을구하였다. 대상환자의비만도를측정하기위하여몸무게 (kg) 를키 (m) 의제곱으로나눈체질량지수 (body mass index) 를구하였다. 고지혈증은 ATP(Adult Treatment Panel) Ⅲ에서의분류 17) 를참고하여총콜레스테롤 240 mg/dl 이상이거나저밀도지단백 160 mg/dl 이상이거나고밀도지단백 40 mg/dl 미만이거나중성지방 200 mg/dl 이상인경우로정의하였다. 당뇨는현재치료중이거나새로진단된경우로정의하였고, 흡연은 1년이내에흡연력이있는경우로정의하였다. 심초음파를이용한좌심실비대의평가 257 명을대상으로 SONOS 5500(HEWLETT PA- CKARD) 심초음파기로 4 MHz transducer 를사용하여 M-mode 심초음파도를기록하여좌심실의확장기말내경 (LVID), 심실중격두께 (IVST) 와좌심실후벽두께 (LV- PWT) 를측정하였으며, 좌심실질량 (LV mass) 은 cube formula를이용한 corrected ASE method 18) 로계산하였고이를체표면적 (BSA) 으로나누어좌심실질량지수 (LV mass index) 를구하였다. ASE-cube LV mass(g)= 1.04[(LVID+IVST+LVPWT) 3 -LVID 3 ] LV mass by corrected ASE method (LVM ASE)= 0.8(ASE-cube LV mass)+0.6 LV mass index(lvmi)=lvmase/bsa(g/m 2 ) 좌심실비대는정상인의좌심실질량지수의평균에 143
표준편차를더한값인정상상한치를기준으로하였고, Shub 등에의해보고된남자 129 g/m 2, 여자 118 g/m 2 이상인경우로정의하였다. 19) 관동맥조영술을이용한관동맥질환의평가 265 명을대상으로 Judkins 방법으로관동맥조영술을시행하고좌전하행지, 좌회선동맥, 우관상동맥의 3개의주요동맥에대해내경협착이 70% 이상인경우유의한협착으로정의하였다. 20) 통계분석응용통계프로그램인 window용 SPSS 10.0를사용하여통계적분석을하였다. 연속변수에대해서는평균 ± 표준편차로표시하였고, 두집단간평균치의비교를위해서는 t-test, 세집단간평균치의비교를위해서는 one way ANOVA 를사용하였다. 비연속변수에대한두집단간비교는 Chi-square test 를사용하였다. 다변량분석을위해서로지스틱회귀분석을사용하였고, 혈압요소의좌심실비대나관동맥질환대한위험도는혈압 10 mmhg 증가에대한교차비 (odds ratio) 로나타내었다. 다변량분석에서단일혈압모델에서는세개의혈압요소중한개씩만을회귀모델에포함하여분석하였고, 복수혈압모델에서는세개의혈압요소들사이에다중공선성 (multicollinearity) 이존재하여세개를함께회귀모델에포함시키는것은불가능하여두개씩포함하였으며, 연령등다른위험인자들은각각단변량분석에서통계적으로유의할때만다변량분석에포함하였다. p값이 0.05 미만일때통계적으로유의한것으로정의하였다. 결과 심초음파를이용한좌심실비대와혈압요소의관련성연구대상의특성전체 257 명가운데좌심실비대가없는군은 198 명 (77%), 좌심실비대가있는군은 59명 (23%) 이었다. 나이는각각 47.2±15.0세, 55.4±10.0 세로차이가있었지만 (p<0.01), 성별, 당뇨, 흡연, 고지혈증, 체질량지수에는두군간에차이가없었다. 혈압요소들을비교하 Table 1. Clinical characteristics according to LVH status No LVH (n=198) LVH (n=59) Age, yr 047.2±15.0 055.4±10.0 <0.001 Male 111 (56.1%) 26 (44.1%) NS* Diabetes 003 (1.5%) 03 (05.1%) NS* Smoker 081 (41.3%) 21 (35.6%) NS* Hyperlipidemia 046 (30.7%) 15 (28.3%) NS* BMI kg/m 2 023.7±03.6 025.0±02.8 <0.009 BP mmhg SBP 134.6±23.4 159.7±23.0 <0.001 DBP 082.8±14.8 097.6±15.8 <0.001 MBP 100.1±16.8 118.3±17.0 <0.001 PP 051.8±14.0 062.2±18.4 <0.001 Values are mean±sd or number of patients (%). *: Fisher s exact test, NS: no statistical significance, LVH: left ventricular hypertrophy, BMI: body mass index, BP: blood pressure, SBP: systolic blood pressure, DBP: diastolic blood pressure, MBP: mean blood pressure, PP: pulse pressure 면좌심실비대군에서수축기혈압, 확장기혈압, 평균혈압, 맥압의평균값이더높았다 (p<0.01)(table 1). 혈압요소들과좌심실질량지수와의상관관계좌심실비대와의상관계수가수축기혈압은 0.497, 확장기혈압은 0.461, 평균혈압은 0.502, 맥압은 0.332로서모두뚜렷한양성선형관계를보였다 (p<0.01). 전체연령군에서의로지스틱회귀분석혈압요소이외의좌심실비대에대한위험인자들이포함된로지스틱회귀모델에혈압요소중 1개만을포함시켜분석한단일혈압모델에서, 수축기혈압, 확장기혈압, 맥압의좌심실비대에대한위험도 ( 혈압이 10 mmhg 씩증가할때마다의교차비 ) 는각각 1.52, 1.91, 1.46 으로확장기혈압의위험도가가장높았다 (p<0.01). 혈압요소중 2개를함께포함한복수혈압모델에서는수축기혈압이나확장기혈압은맥압과함께포함되었을때위험도가맥압보다더높았고 (p<0.01), 수축기혈압과확장기혈압을함께모델에포함하면확장기혈압의위험도가 1.39 로수축기혈압보다더높았다 (p<0.05)(table 2). 연령군에따른로지스틱회귀분석연령군을 50세미만, 50~59 세, 60세이상의세집단 p 144 Korean Circulation J 2004;34(2):142-150
Table 2. Logistic regression models relating LVH to single or dual BP indexes Single BP component (a) β(se) Wald χ 2 p OR (95% CI) SBP -0.42 (0.08) 31.1 <0.001 1.52 (1.31-1.76) DBP -0.65 (0.12) 29.6 <0.001 1.91 (1.51-2.41) PP -0.38 (0.10) 13.6 <0.001 1.46 (1.19-1.78) Dual BP components (b) Model 1 SBP -0.58 (0.12) 23.6 <0.001 1.80 (1.42-2.27) PP -0.30 (0.16) 03.4 <0.067 0.74 (0.54-1.02) Model 2 DBP -0.59 (0.12) 24.0 <0.001 1.80 (1.42-2.28) PP -0.27 (0.11) 06.3 <0.012 1.30 (1.06-1.60) Model 3 SBP -0.27 (0.10) 06.7 <0.010 1.31 (1.07-1.61) DBP 0.33 (0.16) 04.1 <0.043 1.39 (1.01-1.92) Odds ratio (OR) was associated with a 10 mmhg increase in BP. Each BP variable was added to a model that contains covariates and (a) no other BP variable, or (b) one other BP variable. Adjusted for age, male, diabetes, smoking, hyperlipidemia, and BMI. Wald χ 2 =(β/se) 2, LVH: left ventricular hypertrophy, BP: blood pressure, SBP: systolic blood pressure, DBP: diastolic blood pressure, PP: pulse pressure, SE: standard error, CI: confidence interval Table 3. Logistic regression models relating LVH to single BP index by age groups Age<50 yr β(se) Wald χ 2 p OR (95% CI) SBP 0.57 (0.15) 13.6 <0.001 1.77 (1.31-2.39) DBP 0.91 (0.22) 17.4 <0.001 2.47 (1.62-3.79) PP 0.26 (0.20) 01.6 NS 1.30 (0.87-1.93) Age 50-59 yr SBP 0.30 (0.12) 06.6 <0.010 1.35 (1.08-1.70) DBP 0.50 (0.21) 05.5 <0.019 1.65 (1.09-2.50) PP 0.30 (0.15) 03.9 <0.048 1.36 (1.00-1.83) Age 60 yr SBP 0.52 (0.16) 10.5 <0.001 1.67 (1.23-2.29) DBP 0.45 (0.20) 05.0 <0.025 1.56 (1.06-2.31) PP 0.78 (0.25) 09.7 <0.002 2.17 (1.34-3.54) Odds ratio (OR) was associated with a 10 mmhg increase in BP. SBP, DBP, PP were entered in separate models, adjusted for age, male, diabetes, smoking, hyperlipidemia, and BMI. LVH: eft ventricular hypertrophy, BP: blood pressure, SBP: systolic blood pressure, DBP: diastolic blood pressure, PP: pulse pressure, SE: standard error, CI: confidence interval 으로나누어살펴보면, 단일혈압모델인경우 50세미만의연령군에서혈압이외의다른위험인자를보정한위험도는수축기혈압은 1.77, 확장기혈압은 2.47, 맥압은 1.30 으로확장기혈압이가장높았다 (p<0.01). 50~59 세의연령군에서위험도는수축기혈압은 1.35, 확장기혈압은 1.65, 맥압은 1.36 이었다 (p<0.05). 60세이상의연령군에서위험도는수축기혈압은 1.67, 확장기혈압은 1.56, 맥압은 2.17 로맥압이가장높았다 (p<0.01) (Table 3). 복수혈압모델인경우 50세미만의연령군에서수축기혈압이나확장기혈압은맥압보다위험도가 더높았고 (p<0.01), 수축기혈압을함께고려할때확장기혈압의위험도는 2.23 으로더높았다 (p<0.05). 50~ 59세의연령군에서수축기혈압의위험도는 1.49, 확장기혈압은 1.52 로경계성의유의성을보였지만 (p<0.10), 맥압은통계적으로유의하지않았다. 60세이상의연령군에서맥압은확장기혈압과함께모델에포함될때위험도가더높았다 (p<0.01). 확장기혈압을함께고려할때수축기혈압의위험도는 2.12 로서단일혈압모델에서의수축기혈압위험도인 1.67 보다더높았지만 (p<0.01), 확장기혈압의위험도는통계적으로유의하지 145
않았다 (p=0.208). 관동맥조영술을이용한관동맥질환과혈압요소와의관련성 좌심실비대에대한맥압지표 Receiver operating characteristic(roc) curve법을이용하여구한민감도와특이도의합이가장큰맥압값은 50.5 mmhg 였으며, 50 mmhg 를기준으로맥압과좌심실비대의교차표을구하면민감도와특이도는각각 75%, 58% 로통계적으로유의하였고 (p<0.01), 이때맥압이 50 mmhg 이상인경우좌심실비대의위험도 (odds ratio) 는 3.20였다. 연구대상의특성전체 265 명가운데관동맥질환이없는군은 181 명 (68%), 관동맥질환이있는군은 84명 (32%) 이었다. 나이는각각 53.8±11.6세, 60.6±11.5 세로차이가있었고 (p<0.01), 관동맥질환군에서남자, 당뇨, 흡연, 고지혈증의빈도가더높았다 (p<0.01). 혈압요소들을비교하면관동맥질환군에서맥압만이더높았고 (p<0.05), 다른혈압요소에서는유의한차이가없었다 (Table 4). Table 4. Clinical characteristics according to CAD status No CAD (n=181) CAD (n=84) Age, yr 053.8±11.6 060.6±11.5 <0.001 Male 78 (43.1%) 55 (65.5%) <0.001 Diabetes 15 (08.3%) 18 (21.7%) <0.004 Smoker 53 (29.6%) 46 (44.8%) <0.001 Hyperlipidemia 63 (39.4%) 47 (58.0%) <0.006 BMI, kg/m 2 024.6±4.5 024.2±2.9 NS BP, mmhg SBP 138.9±25.1 142.5±22.3 NS DBP 087.2±13.5 085.8±10.7 NS MBP 104.4±16.6 104.7±13.3 NS PP 051.6±16.2 056.6±17.2 <0.023 Values are mean±sd or number of patients (%). NS: no statistical significance, CAD: coronary artery disease, BMI: body mass index, BP: blood pressure, SBP: systolic blood pressure, DBP: diastolic blood pressure, MBP: mean blood pressure, PP: pulse pressure p 전체연령군에서의로지스틱회귀분석단일혈압모델에서관동맥질환에대한다른위험인자를보정한위험도가맥압만이 1.21 로유의하였다 (p<0.05). 복수혈압모델에서맥압은수축기혈압이나확장기혈압과함께모델에포함될때맥압만이유의하게위험도가더높았고 (p<0.05), 수축기혈압과확장기혈압을함께고려하면수축기혈압은증가할수록 (OR 1.23, p<0.05), 확장기혈압은감소할수록 (OR 0.71, p=0.057) 관동맥질환의위험도가증가하였다 (Table 5). 연령군에따른로지스틱회귀분석연령군을 50세미만, 50~59 세, 60세이상의세집단으로나누어살펴보면, 단일혈압모델인경우 50세미만의연령군에서맥압의위험도만 1.53 으로경계성의유의성을보였고 (p=0.062), 나머지연령군에서는세가지 Table 5. Logistic regression model relating CAD to single or dual BP indexes Single BP component (a) β(se) Wald χ 2 p OR (95% CI) SBP -0.07 (0.07) 1.1 NS 1.07 (0.94-1.22) DBP -0.08 (0.12) 0.4 NS 0.93 (0.73-1.18) PP -0.19 (0.10) 4.0 0.046 1.21 (1.00-1.46) Dual BP components (b) Model 1 SBP -0.17 (0.13) 1.7 NS 0.85 (0.66-1.09) PP -0.40 (0.19) 4.6 0.032 1.49 (1.03-2.14) Model 2 DBP -0.15 (0.13) 1.5 NS 0.86 (0.67-1.10) PP -0.23 (0.10) 5.0 0.026 1.26 (1.03-1.54) Model 3 SBP -0.21 (0.10) 4.2 0.040 1.23 (1.01-1.49) DBP -0.34 (0.18) 3.6 0.057 0.71 (0.51-1.01) Odds ratio (OR) was associated with a 10 mmhg increase in BP. Each BP variable was added to a model that contains covariates and (a) no other BP variable, or (b) one other BP variable. Adjusted for age, sex, diabetes, smoking, hyperlipidemia, and BMI. CAD: coronary artery disease, BP: blood pressure, SBP: systolic blood pressure, DBP: diastolic blood pressure, PP: pulse pressure, SE: standard error, CI: confidence interval 146 Korean Circulation J 2004;34(2):142-150
Table 6. Logistic regression models relating CAD to single BP index by age groups Age<50 yr β(se) Wald χ 2 p OR (95% CI) SBP -0.13 (0.13) 1.0 NS 1.14 (0.88-1.47) DBP -0.09 (0.24) 0.2 NS 0.91 (0.57-1.45) PP -0.42 (0.23) 3.5 0.062 1.53 (0.98-2.38) Age 50-59 yr SBP -0.04 (0.13) 1.1 NS 0.96 (0.74-1.23) DBP -0.30 (0.22) 1.8 NS 0.75 (0.48-1.15) PP -0.10 (0.18) 0.3 NS 1.11 (0.78-1.58) Age 60 yr SBP -0.11 (0.10) 1.3 NS 1.12 (0.92-1.36) DBP -0.03 (0.19) 0.0 NS 1.03 (0.71-1.50) PP -0.20 (0.13) 2.3 NS 1.22 (0.94-1.58) Odds ratio (OR) was associated with a 10 mmhg increase in BP. SBP, DBP, PP were entered in separate models, adjusted for age, sex, diabetes, smoking, hyperlipidemia, and BMI. CAD: coronary artery disease, BP: blood pressure, SBP: systolic blood pressure, DBP: diastolic blood pressure, PP: pulse pressure, SE: standard error, CI: confidence interval 혈압요소중어느것도관동맥질환과유의한연관성이없었다 (Table 6). 복수혈압모델인경우 50 세미만의연령군에서맥압은수축기혈압이나확장기혈압과함께모델에포함될때맥압의위험도가더높았고 (p<0.10, p<0.05), 수축기혈압과확장기혈압을함께고려하면수축기혈압의위험도가더높았다 (p<0.05). 50~59 세또는 60세이상의연령군에서는세개의혈압요소위험도모두통계적으로유의하지않았다. 관동맥질환에대한맥압지표 ROC curve 법을이용하여구한민감도와특이도의합이가장큰맥압값은 49.5, 61.5 mmhg 였으며, 좌심실비대와같이 50 mmhg 를기준으로맥압과관동맥질환의교차표을만들면민감도와특이도는각각 72%, 47% 로통계적으로유의하였고 (p<0.01), 이때맥압이 50 mmhg 이상인경우관동맥질환의위험도 (odds ratio) 는 2.09였다. 고찰 2001년 Framingham Heart Study에 Framingham Offsping Study 를결합하여전체연령을대상으로한연구에서, 연령이증가할수록관동맥질환의예측인자는확장기혈압에서수축기혈압으로그리고다시맥압으로점 진적으로이동하여, 50세이하에서는확장기혈압이가장강력한예측인자이고, 50~59 세에는이행기로서세혈압요소모두비슷하지만, 60세이후에는확장기혈압은관동맥질환과음의상관관계를보여서맥압이수축기혈압보다더좋은예측인자라고보고하였다. 16) 이번연구결과좌심실비대에대한위험도는 50세미만에서는확장기혈압이다른혈압요소보다더높았고, 50대에는확장기혈압의위험도는감소하고맥압및수축기혈압의위험도는증가하는추세를보였으며, 60세이후에는위험도가맥압 > 수축기혈압 > 확장기혈압의순서로, 연령이증가할수록좌심실비대와관련된지표로서확장기혈압의중요성은감소하고맥압과수축기혈압의중요성은증가하였다. 한편관동맥질환에대한위험도는전체연령을대상으로했을때맥압의위험도가 1.21 로가장높았는데, 수축기혈압과확장기혈압을함께고려하면수축기혈압의위험도는 1.23 으로수축기혈압단독위험도인 1.07 보다높았고, 수축기혈압이증가하면서동시에확장기혈압이감소할수록위험도가증가하여맥압이증가함에따라위험도가증가한다는사실과일치하였다. 맥압이 50 mmhg 이상인경우에그렇지않은경우보다좌심실비대의위험도는약 3배정도높았고관동맥질환의위험도는약 2배정도높아서, 맥압의증가로혈압측정당시의심혈관질환의위험성을추정하는데의의가있음을보였다. 147
1997년 Framingham Heart Study에서, 50세까지는수축기혈압과확장기혈압이함께평행하게증가하다가 60세이후부터수축기혈압은지속적으로증가하는반면확장기혈압은감소하여맥압이크게증가한다고보고하였다. 21) 심장에서혈액이박출되면상행대동맥은확장되고투사파와반사파의중첩에의하여맥파 (pulse wave) 를만들게되는데투사파는좌심실구출과동맥의경직에의해좌우되고반사파는동맥의경직과맥파의반사지점과연관이있다. 젊은연령에서는나이가증가함에따라말초혈관저항의증가로수축기혈압과확장기혈압이함께상승하고동맥의신전성이크기때문에맥파의전파속도가느려반사파가주로확장기때나타난다. 그러나, 나이가들면동맥은콜라겐섬유와칼슘이침착되고탄력층이변성됨에따라내막과중막의두께가증가하여경화가진행되는구조적변화와내피세포의존성혈관확장의감소등여러기능적인변화가함께일어난다. 동맥의경직도증가는중심성탄력동맥에서두드러지게나타나기때문에맥파의전파속도가빨라져반사파가수축후기때일찍나타나수축기혈압과맥압은점차커지고대동맥탄성감소로확장기혈압은감소하게된다. 3)16)21-25) 이번좌심실비대에관한연구에서 60세이상의복수혈압모델에서수축기혈압이증가할수록좌심실비대의위험도는증가하였지만 (OR 2.12, p<0.01), 확장기혈압은좌심실비대와통계적으로관련성이없었다 (OR 0.65, p=ns). 그이유는연령증가에따른중심동맥의경직과이로인한후부하의증가가좌심실비대의발생에주요한역할을하기때문으로생각된다. Gasowski 등 8) 에의한연구에서보면일정한수축기혈압에서맥압이증가한경우가일정한맥압에서수축기혈압이증가한경우보다관동맥질환과더관련되어있다고보고하였고, 이는관동맥질환의위험이말초혈관저항에의한안정성스트레스보다는중심동맥경직에의한박동성스트레스와더관련되어있음을시사해준다. 이번연구에서전체연령군에서맥압의관동맥질환에대한위험도가가장높았고, 수축기혈압의위험도가단일혈압모델에서 1.07 이었던반면에수축기혈압과확장기혈압의복수혈압모델에서는 1.23 으로증가하였고, 복수혈압모델에서수축기혈압이증가할수록 (OR 1.23, p<0.05) 동시에확장기혈압이감소할수록관동 맥질환이증가하였다 (OR 0.71, p=0.057). 이러한결과로부터맥압이수축기혈압이나확장기혈압보다관동맥질환과더관련된혈압요소임을알수있었고, 그이유는연령이증가할수록중심동맥의경직으로인한확장기혈압의감소와이로인한관동맥혈류의감소가관동맥질환의발생에주요한역할을하기때문으로생각된다. 그러나, 고연령군에서는세가지혈압요소모두관동맥질환발생과관련이없었고나이, 남자, 당뇨의다른위험인자들이더많이관련된것으로나타났다. 한편, 관동맥질환군에서나이가많고질병이중증인경우가더많았는데이경우좌심실기능장애등으로인해혈압요소들이오히려감소하는경향을보여관동맥질환군과정상군사이에유의한차이가없어졌을것으로생각된다. 이러한맥압의상승과심혈관계합병증과의관계는양방향성의개념으로설명할수있는데, 상승된맥압이혈관손상을유발하여동맥경화를진행시키고, 동맥경화에의해중심동맥의경직도가증가하여맥파의반향이증가하므로더맥파를증폭시킨다. 이고리에서상승된맥압이동맥경화의원인일수도있고그결과일수도있는것이다. 26) 결론적으로좌심실비대와관련성이가장큰혈압요소지표는나이에따라변하여, 50세미만에서는확장기혈압이가장중요한지표였으나, 50~59 세에서는확장기혈압의중요성이감소하여, 60세이후에서는맥압과수축기혈압이가장중요한지표가되었고, 이는중심동맥경직도증가와관련된것으로생각된다. 반면에관동맥질환과의관련성이가장큰혈압요소지표는전체연령군에서맥압이었으나, 고연령군에서는세가지혈압요소중어느것도유의한지표가아니었고, 이는고혈압이외의다른심혈관질환위험인자들이더많은관련성을가지기때문으로생각된다. 요약 배경및목적 : 혈압의어느요소가심혈관질환의위험도를예측하는데상대적으로가장중요한가에대해서는아직확실하지않다. 최근에여러추적관찰연구에서 60세이상에서맥압이관동맥질환의가장강력한예측인자라고보 148 Korean Circulation J 2004;34(2):142-150
고하였다. 이에좌심실비대와관동맥질환의위험도에대한수축기혈압, 확장기혈압, 맥압의상대적중요성을서로다른연령군에서비교해보았다. 방법 : 고혈압약을복용하지않는 257 명을대상으로 M- mode 심초음파를이용하여좌심실질량지수를구하여남자 129 g/m 2, 여자 118 g/m 2 이상인경우좌심실비대로정의하였고, 또다른고혈압약을복용하지않는 265명을대상으로관동맥조영술을시행하여내경협착이 70% 이상인경우관동맥질환으로진단하였고, 로지스틱회귀분석을통하여좌심실비대및관동맥질환에가장큰영향을주는혈압요소를알아보았다. 결과 : 좌심실비대에대한위험도는 50세미만에서는확장기혈압 2.47, 수축기혈압 1.77, 맥압 1.30(10 mmhg 증가마다 ) 이었고, 50~59 세에서는확장기혈압 1.65, 수축기혈압 1.35, 맥압 1.36 이었고, 60세이상에서는확장기혈압 1.56, 수축기혈압 1.67, 맥압 2.17 이었다. 관동맥질환에대한위험도는전체연령군에서확장기혈압 0.93, 수축기혈압 1.07, 맥압 1.21 이었다. 그러나 60 세이상의연령군에서는세가지혈압요소중어느것도통계적으로유의하지않았다. 결론 : 좌심실비대와관련성이가장큰혈압요소지표는연령이증가할수록확장기혈압에서수축기혈압으로다시맥압으로이동하였다. 50대까지는확장기혈압이가장중요한지표이지만그중요성이점차감소하여 60세이후에서는맥압과다음으로수축기혈압이가장중요한지표였다. 관동맥질환과관련성이가장큰혈압요소지표는전체연령에서맥압이지만 60세이후에서는어느혈압요소도유의한관련성이없었다. 중심단어 : 혈압 ; 맥압 ; 좌심실비대 ; 관동맥질환. REFERENCES 1) Kannel WB, Gordon T, Schwartz MJ. Systolic versus diastolic blood pressure and risk of coronary heart disease. Am J Cardiol 1971;27:335-46. 2) Staessen JA, Gasowski J, Wang JG, Thijs L, den Hond E, Boissel JP, Coope J, Ekbom T, Gueyffier F, Liu L, Kerlikowske K, Pocock S, Fagard RH. Risks of untreated and treated isolated systolic hypertension in the elderly: metaanalysis of outcome trials. Lancet 2000;355:865-72. 3) Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease? Circulation 1999;100:354-60. 4) Casiglia E, Tikhonoff V, Mazza A, Piccoli A, Pessina AC. Pulse pressure and coronary mortality in elderly men and wemon from general population. J Hum Hypertens 2002; 16:611-20. 5) Safar ME. Pulse pressure, arterial stiffness, and cardiovascular risk. Curr Opin Cardiol 2000;15:258-63. 6) Sesso HD, Stampfer MJ, Rosner B, Hennekens CH, Gaziano JM, Manson JE, Glynn RJ. Systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure as predictors of cardiovascular disease risk in men. Hypertension 2000;36:801-7. 7) Darne B, Girerd X, Safar M, Cambien F, Guize L. Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis on cardiovascular mortality. Hypertension 1989;13:392-400. 8) Gasowski J, Fagard RH, Staessen JA, Grodzicki T, Pocock S, Boutitie F, Gueyffier F, Boissel JP. Pulsatile blood pressure component as predictor of mortality in hypertension: a meta-analysis of clinical trial control groups. J Hypertens 2002;20:145-51. 9) Vaccarino V, Berger AK, Abramson J, Black HR, Setaro JF, Davey JA, Krumholz HM. Pulse pressure and risk of cardiovascular events in the systolic hypertension in the elderly program. Am J Cardiol 2001;88:980-6. 10) Mitchell GF, Moye LA, Braunwald E, Rouleau JL, Bernstein V, Geltman EM, Flaker GC, Pfeffer MA. Sphygmomanometrically determined pulse pressure is a powerful independent predictor of recurrent events after myocardial infacrtion in patients with impaired left ventricular function. Circulation 1997;96:4254-60. 11) Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in endstage renal disease. Circualtion 1999;99:2434-9. 12) Brahimi M, Dahan M, Dabire H, Levy BI. Impact of pulse pressure on degree of cardiac hypertrophy in patients with chronic uraemia. J Hypertens 2000;18:1645-50. 13) Kim DK, Goo YS, Kim HJ, Kim HJ, Lee TH, Maeng HY, Hong SP, Kim YS, Jung IH, Choi HY, Kang SW, Choi KH, Lee HY, Han DS. Risk factors of left ventricular hypertrophy in CAPD patients. Korean J Nephrol 2002;21:966-74. 14) Pannier B, Brunel P, el Aroussy W, Lacolley P, Safar ME. Pulse pressure and echocardiographic findings in essential hypertension. J Hypertens 1989;7:127-32. 15) Domanski MJ, Davis BR, Pfeffer MA, Kastantin M, Mitchell GF. Isolated systolic hypertension: prognostic information provided by pulse pressure. Hypertension 1999;34:375-80. 16) Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, Kannel WB, Levy D. Does the relation of blood pressure to coronary heart disease risk change with aging? Circulation 2001;103:1245-9. 17) Expert Panel on Detection, Evaluation and Treatment of High Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NC- EP) expert panel on detection, evaluation, evaluation, and treatment of the high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285:2486-97. 18) Oh JK, Seward JB, Tajik AJ. The echo manual. 2nd ed. 149
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