Risk Stratification by BMI and ABP -1-
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Journal of Human Hypertension
Risk Stratification by BMI and ABP -1-
Ambulatory Blood Pressure Monitoring for Risk Stratification
in Obese and Non-Obese Subjects from 10 Populations
Short title: Risk Stratification by BMI and ABP
Tine W. Hansen, MD, PhD; Lutgarde Thijs, MSc; Yan Li, MD, PhD; José Boggia, MD, PhD;
Yanping Liu, MD; Kei Asayama, MD, PhD; Masahiro KikuyaMD, PhD; Kristina Björklund-Bodegård, MD, PhD; Takayoshi Ohkubo,MD, PhD; Jørgen Jeppesen, MD, PhD; Christian TorpPedersen, MD, PhD; Eamon Dolan, MD, PhD; Tatiana Kuznetsova, MD, PhD; Katarzyna Stolarz-Skrzypek, MD, PhD; Valérie Tikhonoff, MD, PhD;
Sofia Malyutina, MD, PhD; Edoardo Casiglia MD, PhD; Yuri Nikitin, MD, PhD; Lars Lind, MD, PhD;
Edgardo Sandoya, MD, PhD; Kalina Kawecka-Jaszcz, MD, PhD; Jan Filipovský, MD, PhD;
Yutaka Imai, MD, PhD; Jiguang Wang, MD, PhD; Eoin O’Brien, MD, PhD;
Jan A. Staessen, MD, PhD; on behalf of the International Database on Ambulatory blood pressure
in relation to Cardiovascular Outcomes (IDACO) Investigators
Word Counts: Manuscript 7261, Body of Manuscript, 3529, Abstract 200
Number: Tables 3, Figures 3
Correspondence and requests for reprintsto:
Jan A. Staessen, MD, PhD,
Studies Coordinating Centre,
Laboratory of Hypertension,
University of Leuven,
Campus Sint Rafaël,
Kapucijnenvoer 35, Block D, Box 7001,
BE3000 Leuven, Belgium
Telephone: +32-16-34-7104 (office)
+32-15-41-1747 (home)
+32-47-632-4928 (mobile)
Facsimile: +32-16-34-7106 (office)
+32-15-41-4542 (home)
email:
Risk Stratification by BMI and ABP -1-
Authors Affiliations: Steno Diabetes Centre, Gentofte and Research Centre for Prevention and Health, Glostrup, Denmark (Dr Hansen); Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Sciences, University of Leuven, Belgium (Drs Thijs, Liu, Asayama, Kuznetsova, and Staessen); Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan (Drs Asayama, Kikuya, and Imai); Center for Epidemiological Studies and Clinical Trials (Drs Li and Wang) and Center for Vascular Evaluation (Dr Li), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Centro de Nefrología and Departamento de Fisiopatología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay (Dr Boggia); Section of Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden (Drs Björklund-Bodegård and Lind ); Department of Health Sciences, Shiga University of Medical Sciences, Otsu, Japan (Dr Ohkubo); Copenhagen University Hospital, Copenhagen, Denmark (Drs. Jeppesen and Torp-Pedersen); Cambridge University Hospitals, Addenbrook’s Hospital, Cambridge, United Kingdom (Dr Dolan); First Department of Cardiology and Hypertension, Jagiellonian University Medical College, Kra-ków, Poland (Drs Stolarz-Skrzypek and Kawecka-Jaszcz); Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy (Drs Tikhonoff and Casiglia); Insti-tute of Internal Medicine, Novosibirsk, Russian Federation (Drs Malyutina and Nikitin); the Asociación Española Primera de Socorros Mutuos, Montevideo, Uruguay (Dr Sandoya); Faculty of Medicine, Charles University, Pilsen, Czech Republic (Dr Filipovský); the Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland (Dr O’Brien); and the Department of Epidemiology, Maastricht University, Maastricht, The Netherlands (Dr Staessen). The IDACO investigators are listed in reference 16.
Corresponding Author: Jan A. Staessen, MD, PhD, Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Sciences, University of Leuven, Campus Sint Rafaël, Kapucijnenvoer 35, Block D, Box 7001, BE3000 Leuven, Belgium.
Email: .
Expanded Methods
Study population
As described in detail elsewhere(1), we constructed the International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes (IDACO). Studies were eligible for inclusion, if they involved a random population sample, if baseline information on the ambulatory BP and cardiovascular risk factors was available, and if the subsequent follow-up included both fatal and nonfatal outcomes. Baseline information for each cohort are shown in Table S1. All studies received ethical approval and have been reported in peer-reviewed publications.
Analyzed participants were 2,142 residents from Copenhagen, Denmark(2); 1,317 inhabitants from Ohasama, Japan(3); 1,096 subjects from Noorderkempen, Belgium(4); 1,098 older men from Uppsala, Sweden(5); 1,438 subjects from Montevideo, Uruguay(6);349 villagers from the JingNing county, China(7);244 subjects from Novosibirsk, the Russian Federation(8); 165 from Pilsen, Czech Republic(9); 310 from Padova, Italy(9); and 308 from Kraków, Poland(9). All participants gave informed written consent. Subjects recruited in Kraków, Novosibirsk, Pilsen, and Padova took part in the European Project on Genes in Hypertension (EPOGH)(9). All participants gave informed written consent.
BPmeasurement
Conventional BP was measured by trained observers with a mercury sphygmomanometer(7;9;10), with validated auscultatory(3) (USM-700F, UEDA Electronic Works, Tokyo, Japan) or oscillometric(6) (OMRON HEM-705CP, Omron Corporation, Tokyo, Japan) devices, using the appropriate cuff size, with participants in the sitting(3;4;6-10) or supine(5) position. Conventional BP was the average of 2 consecutive readings obtained either at the person’s home(4;6-9) or at an examination center(3;5;10). We programmed portable monitors to obtain ambulatory BP readings at 30 minute intervals throughout the whole day(3), or at intervals ranging from 15(10) to 30(5) minutes during daytime and from 30(10) to 60(5) minutes at night. The devices implemented an auscultatory algorithm (Accutracker II) in Uppsala(5) or an oscillometric technique (SpaceLabs 90202 and 90207, Nippon Colin, and ABPM 630) in the other cohorts(3-9).
The same SAS macro processed all ambulatory recordings, which generally stayed unedited. The Ohasama recordings were edited sparsely according to previously published criteria(11). Within individual subjects, we weighted the means of the ambulatory BP by the interval between readings. When accounting for the daily pattern of activities of the participants, we defined daytime as the interval ranging from 10:00 h to 20:00 h in people from Europe(4;5;8-10) and South America(6), and from 08:00 h to 18:00 h in those from Asia(3;7). The corresponding night-time intervals ranged from midnight to 06:00 h(4-6;8-10) and from 22:00 h to 04:00 h(3;7). These fixed intervals eliminate the transition periods in the morning and evening when BP changes rapidly, resulting in daytime and night-time BP levels that are within 1–2 mm Hg of the awake and asleep levels(7;12).
In line with current guidelines(13;14), we defined conventional hypertension as a BP equal to or exceeding 140 mm Hg systolic or 90 mm Hg diastolic. The corresponding thresholds for daytime ambulatory hypertension were 135 mm Hg systolic and 85 mm Hg diastolic. Patients on antihypertensive drug treatment were classified according to the achieved BP. Normotension and sustained hypertension were a consistently normal or consistently elevated BP on conventional and ambulatory measurement(13;14). White-coat hypertension was a raised conventional BP in the presence of a normal daytime BP(13;14). Masked hypertension was an elevated ambulatory BP with normal conventional BP(13;14).
Irregular heart rate was defined as an average real variability of 24-h heart rate (ARV24) in the highest decile (≥12.05).The ARVaverages the absolute differences of consecutive measurements and accounts in this manner for the order in which the measurements are obtained. It is calculated by the following formula:
where k ranges from 1 to N-1 and wk is the time interval between HRk and HRk+1. N is the number of heart rate readings(15).
References
(1) Thijs L, Hansen TW, Kikuya M, Björklund-Bodegård K, Li Y, Dolan E, et al. The International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome (IDACO) : protocol and research perspectives. Blood Press Monit 2007;12:255-62.
(2) Hansen TW, Jeppesen J, Rasmussen F, Ibsen H, Torp-Pedersen C. Ambulatory blood pressure monitoring and mortality : a population-based study. Hypertension 2005;45:499-504.
(3) Ohkubo T, Hozawa A, Yamaguchi J, Kikuya M, Ohmori K, Michimata M, et al. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure : the Ohasama study. J Hypertens 2002;20:2183-9.
(4) Staessen JA, Bieniaszewski L, O'Brien ET, Imai Y, Fagard R. An epidemiological approach to ambulatory blood pressure monitoring : the Belgian population study. Blood Press Monit 1996;1:13-26.
(5) Ingelsson E, Björklund K, Lind L, Ärnlöv J, Sundström J. Diurnal blood pressure pattern and risk of congestive heart failure. JAMA 2006;295:2859-66.
(6) Schettini C, Bianchi M, Nieto F, Sandoya E, Senra H, Hypertension Working Group. Ambulatory blood pressure. Normality and comparison with other measurements. Hypertension 1999;34 (part 2):818-25.
(7) Li Y, Wang JG, Gao HF, Nawrot T, Wang GL, Qian YS, et al. Are published characteristics of the ambulatory blood pressure generalizable to rural Chinese? The JingNing population study. Blood Press Monit 2005;10:125-34.
(8) Kuznetsova T, Malyutina S, Pello E, Thijs L, Nikitin Y, Staessen JA. Ambulatory blood pressure of adults in Novosibirsk, Russia : interim report on a population study. Blood Press Monit 2000;5:291-6.
(9) Kuznetsova T, Staessen JA, Kawecka-Jaszcz K, Babeanu S, Casiglia E, Filipovský J, et al. Quality control of the blood pressure phenotype in the European Project on Genes in Hypertension. Blood Press Monit 2002;7:215-24.
(10) Hansen TW, Jeppesen J, Rasmussen S, Ibsen H, Torp-Pedersen C. Ambulatory blood pressure monitoring and risk of cardiovascular disease: a population based study. Am J Hypertens 2006;19:243-50.
(11) Ohkubo T, Imai Y, Tsuji I, Nagai K, Ito S, Satoh H, et al. Reference values for 24-hour ambulatory blood pressure monitoring based on a prognositic criterion. The Ohasama Study. Hypertension 1998;32:255-9.
(12) Fagard R, Brguljan J, Thijs L, Staessen J. Prediction of the actual awake and asleep blood pressures by various methods of 24 h pressure analysis. J Hypertens 1996;14:557-63.
(13) O'Brien E, Asmar R, Beilin L, Imai Y, Mancia G, Mengden T, et al. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. J Hypertens 2005;23:697-701.
(14) Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jr., et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206-52.
15) Mena L, Pintos S, Queipo NV, Aizpúrua JA, Maestre G, Sulbarán T. A reliable index for the prognostic significance of blood pressure variability. J Hypertens. 2003;23:505-511.
Risk Stratification by BMI and ABP -1-
Table S1. Baseline information for each cohort
Cohortreference / Period of
recruitment / Invited / Participated / Eligible for inclusion in IDACO* / Excluded from the present analyses** / Included in the present analysis
Copenhagen
Hansen TW. Am J Hypertens. 2006; 19(3): 243-59 / 1993-94 / 3,794 / 2,656 (70.0%) / 2,311 / 169 (7.3%) / 2,142
Ohasama
Ohkubo T. J Hyperten. 2002; 20(11): 2183-9 / 1987-91 / 1,989 / 1,542 (77.5%) / 1,535 / 218 (14.2%) / 1,317
Noorderkempen
Li Y. Hypertension. 2007; 49(6): 1291-7 / 1985-2005 / 4,277 / 3,338 (78.0%) / 2,904 / 1,808 (62.3%) / 1,096
Uppsala
Ingelsson E. JAMA. 2006; 295(24): 2859-66 / 1991-95 / 1,681 / 1,221 (72.6%) / 1,143 / 45 (3.9%) / 1,098
Montevideo
Schettini C. Hypertension. 1999; 34 (4 pt 2): 818-25 / 1995-98 / 2,650 / 2,070 (78.1%) / 1,859 / 421 (22.6%) / 1,438
JingNing
Li Y. Blood Press Monit. 2005;10(3):125-34 / 2003-05 / 839 / 509 (60.7%) / 360 / 11 (3.1%) / 349
EPOGH
Stolarz-Skrzypek K. JAMA. 2011; 305(17): 1777-85 / 1999-2001 / 1,721 / 1,187 (68.9%) / 1,055 / 28 (2.6%) / 1,027
EPOGH (European Project on Genes in Hypertension) includes participants recruited at Kraków, Novosibirsk, Padova and Pilsen.
* Having ambulatory blood pressure and covariables measured at baseline and having information on fatal and nonfatal outcomes.
** Excluded because they were younger than 18 years, because their conventional blood pressure had not been measured, or because they had fewer than 10 daytime or 5 nighttime blood pressure readings.
Risk Stratification by BMI and ABP -1-
Table S2. Adjusted hazard ratios according to the cross-classification of participants by conventional and daytime ambulatory blood pressure
Quartiles of BMILimits, kg/m2 / ≤22.6 / >22.6 to ≤25.1 / >25.1 to ≤27.9 / >27.9 / P
Total mortality
White-coat hypertension / 1.34 (0.93, 1.94) / 0.92 (0.62, 1.38) / 1.18 (0.82, 1.72) / 1.04 (0.70, 1.55) / 0.87
Masked hypertension / 1.66 (1.17, 2.36)† / 1.46 (1.03, 2.06)* / 1.04 (0.70, 1.54) / 0.76 (0.50, 1.15) / 0.015
Sustained hypertension / 1.66 (1.23, 2.24)‡ / 1.26 (0.95, 1.68) / 1.21 (0.89, 1.63) / 1.13 (0.83, 1.53) / 0.21
All cardiovascular endpoints
White-coat hypertension / 0.92 (0.56, 1.52) / 0.90 (0.57, 1.43) / 1.45 (0.97, 2.16) / 1.48 (0.93, 2.36) / 0.23
Masked hypertension / 1.83 (1.21, 2.77)† / 1.95 (1.32, 2.89)§ / 1.44 (0.97, 2.15) / 1.21 (0.78, 1.89) / 0.29
Sustained hypertension / 2.18 (1.54, 3.09)‡ / 1.92 (1.34, 2.68)§ / 1.72 (1.25, 2.37)‡ / 1.93 (1.37, 2.75)‡ / 0.37
The definition of the BP categories is given in the eMethods. White-coat, masked and sustained hypertension had a prevalence of 7.9%, 12.2% and 13.6% in the low BMI quartile, 8.5%, 14.0% and 21.2% in the medium-low quartile, 11.7%, 15.5% and 29.6% in the medium-high quartile and 12.8%, 14.0% and 39.9% in the high quartile. Hazard ratios (95% confidence intervals) express the risk of white-coat hypertension, masked hypertension and sustained hypertension vs. normotension in quartiles of BMI. The hazard ratios were stratified for cohort and adjusted for sex, age, smoking and drinking, serum cholesterol, history of cardiovascular disease, diabetes, and treatment with antihypertensive drugs. Significance of the hazard ratios: *≤0.05; †≤0.01; ‡≤0.001. The P-values are for the linear trend in the hazard ratios across the BMI categories.
Risk Stratification by BMI and ABP -1-
Table S3. Hazard ratios for total mortality in relation to BMI category and 24-h systolic BP
Subgroup analyzed(n° of deaths/n) at risk / Quartiles of BMI
Low / Medium-low / Medium-high / High / Pcon / Pint
Europeans and South Americans (980/6,801)
BMI / 1.20 (1.07, 1.35)† / 0.96 (0.86, 1.07) / 0.88 (0.79, 0.98)* / 0.99 (0.89, 1.10) / 0.010 / 0.97
Systolic BP / 1.10 (0.97, 1.26) / 1.16 (1.02, 1.32)* / 1.23 (1.08, 1.40)† / 1.11 (0.99, 1.26)
European and Asians (1,175/7,029)
BMI / 1.21 (1.08, 1.35)‡ / 1.02 (0.92, 1.13) / 0.83 (0.75, 0.92)‡ / 0.98 (0.88, 1.09) / <0.0001 / 0.80
Systolic BP / 1.12 (0.99, 1.25) / 1.22 (1.08, 1.37)‡ / 1.27 (1.13, 1.44)‡ / 1.11 (0.89, 1.23)
Nonsmokers (831/6,037)
BMI / 1.18 (1.03, 1.35)* / 0.96 (0.85, 1.09) / 0.91 (0.85, 1.09) / 0.97 (0.86, 1.10) / 0.11 / 0.39
Systolic BP / 1.19 (1.02, 1.38)* / 1.22 (1.06, 1.42)† / 1.10 (0.94, 1.28) / 1.20 (1.04, 1.38)*
Not treated for hypertension (774/6,648)
BMI / 1.10 (0.95, 1.26) / 1.05 (0.93, 1.18) / 0.91 (0.80, 1.03) / 0.96 (0.85, 1.09) / 0.32 / 0.50
Systolic BP / 1.10 (0.95, 1.27) / 1.25 (1.09, 1.43)† / 1.22 (1.06, 1.41)† / 1.09 (0.95, 1.24)
Subjects with regular 24-h heart rate rhythm (1,131/7,621)
BMI / 1.17 (1.09, 1.26)‡ / 0.99 (0.92, 1.06) / 0.89 (0.83, 0.96)† / 1.01 (0.94, 1.08) / 0.44 / 0.93
Systolic BP / 1.15 (1.02, 1.29)* / 1.20 (1.06, 1.36)† / 1.17 (1.03, 1.33)* / 1.14 (1.02, 1.28)*
Women (396/3,978)
BMI / 1.18 (0.98, 1.42) / 1.13 (0.96, 1.34) / 0.91 (0.79, 1.09) / 0.82 (0.69, 0.98)* / 0.049 / 0.77
Systolic BP / 1.17 (0.95, 1.45) / 1.34 (1.10, 1.64)‡ / 1.23 (0.98, 1.55) / 1.20 (0.97, 1.50)
Men (875/4,489)
BMI / 1.16 (1.02, 1.31)* / 0.93 (0.83, 1.05) / 0.85 (0.76, 0.96)* / 1.08 (0.96 ,1.22) / 0.0084 / 0.89
Systolic BP / 1.10 (0.98, 1.25) / 1.13 (0.99, 1.30) / 1.22 (1.05, 1.40)† / 1.08 (0.96, 1.22)
Hazard ratios (95% confidence intervals) express the risk of death associated with categories of BMI (vs. the average risk in the analyzed population) or for a 1 SD increase in the 24-h BP (~15.0 mm Hg). Hazard ratios were stratified for cohort. In addition to BMI and 24h BP, all models included sex, age, smoking and drinking, serum cholesterol, history of cardiovascular disease, diabetes, and treatment with antihypertensive drugs (where appropriate). Significance of the hazard ratios: * ≤0.05; † ≤0.01; and ‡ ≤0.001. PCon denotes the significance of the likelihood ratio testing the contribution of BMI quartiles to the prediction of death over and beyond BP and Pint expresses the significance of the interaction between BP and BMI
FigureS1. Incidence of death (A) or of a composite cardiovascular endpoint (B) by cross-classification of BMI and conventional systolic BP categorized into quartiles. The incidence rates were standardized for cohort, sex and age (<60 and ≥60 years).
Figure S2. Absolute 10-year risk of death (A) or a composite cardiovascular endpoint (B) in relation to conventional systolic BP in classes of body mass. For clarity, the second and third quartile of BMI were combined, because the risk functions were coincident. Risk estimates were stratified for cohort and adjusted for sex, age, serum cholesterol, smoking and drinking, history of cardiovascular disease, diabetes, and antihypertensive drug treatment. P values are for the independent contributions to risk of BMI and conventional systolic BP.