NEWS & VIEWS public concern.1 Whichever study approach is taken next, it must be credible, not only to the scientific community but also to the general public.
DIABETES
Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850, USA (K.M.). Section of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, 1819 W. Polk Street, MC 640, Chicago, IL 60616, USA (A.B.S.). Correspondence to: K.M. [email protected]
Gianfranco Parati and Alberto Zanchetti
Acknowledgements The authors wish to acknowledge J. Loukissas of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA, who provided valuable insights during the writing of this article. Competing interests A.B.S. has served as an advisor and expert witness for a law firm dealing with radiation releases from the Hanford Nuclear Facility. K.M. declares no competing interests. 1.
National Research Council. Analysis of cancer risks in populations near nuclear facilities: phase 1 (The National Academies Press, 2012). 2. Bollaerts, K. et al. Thyroid cancer incidence in the vicinity of nuclear sites in Belgium, 2000–2008. Thyroid http://dx.doi.org/ 10.1089/thy.2013.0227. 3. Bouville, A., Linet, M. S., Hatch, M., Mabuchi, K. & Simon, S. L. Guidelines for exposure assessment in health risk studies following a nuclear reactor accident. Environ. Health Perspect. 122, 1–5 (2014). 4. Vandecasteele, C. M., Sonck, M. & Degueldre, D. Rejet accidentel d’iode‑131 par l’IRE sur le site de Fleurus: retour d’expérience de l’autorité de sûreté belge [French]. Radioprotection 46, 159–173 (2011). 5. United Nations Scientific Committee on the Effects of Radiation. Sources and effects of ionizing radiation. UNSCEAR 2000: Report to the general assembly with scientific annexes, Volume I [online], http://www.unscear.org/ unscear/en/publications/2000_1.html (2013). 6. Ron, E. et al. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat. Res. 141, 259–277 (1995). 7. Shakhatarin, V. V. et al. Iodine deficiency, radiation dose, and the risk of thyroid cancer among children and adolescents in the Bryansk region of Russia following the Chernobyl power station accident. Int. J. Epidemiol. 32, 584–591 (2003). 8. Davis, S. et al. Risk of thyroid cancer in the Bryask Oblast of the Russian Federation after the Chernobyl power plant station accident. Radiat. Res. 162, 241–248 (2004). 9. Davies, L. & Welch, H. G. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 295, 2164–2167 (2006). 10. Nose, T. & Oiwa, Y. Thyroid cancer cases increase among young people in Fukushima. The Asahi Shimbun [online], http:// ajw.asahi.com/article/0311disaster/ fukushima/AJ201402080047 (2014).
Measuring interarm blood pressure differences in diabetes Interarm differences in systolic blood pressure are associated with a significant risk of morbidity and mortality. A new study reports that these differences are frequently observed in patients with diabetes mellitus and recommends routine measurement of interarm blood pressure differences to improve diagnostic and prognostic stratification of these patients. Parati, G. & Zanchetti, A. Nat. Rev. Endocrinol. 10, 387–388 (2014); published online 3 June 2014; doi:10.1038/nrendo.2014.80
Patients with diabetes mellitus and ele vated blood pressure have a higher risk of cardiovascular disease than normotensive or hypertensive individuals without dia betes mellitus.1 The inaccurate assessment of blood pressure in primary care settings is a contributing factor in the increased cardiovascular risk observed in patients with diabetes mellitus. This increased risk is due not only to the intrinsic limitations of primary care blood pressure measure ments (such as, the inaccuracy of readings obtained under constraints of time, poten tial white coat effects, investigator bias and digit preference, and the inability of limited blood pressure measurements to faithfully reflect normal daily blood pressure), 2 but also to the frequent failure of practicing physicians to follow the guideline recom mendations for measuring blood pressure. One such recommendation consists of mea suring blood pressure in both arms at the first visit to detect possible interarm differ ences, and using the arm with the highest blood pressure value as the reference for making decisions about treatment.3 This recommendation is supported by the asso ciation between interarm differences in systolic blood pressure (≥10 mmHg) and vascular damage, cerebrovascular disease and increased risk of cardiovascular-related and all-cause mortality.4 However, although ~77% of primary care physicians are aware of guideline recommendations for mea suring blood pressure in both arms, only a minority of them (~30%) follow this advice, and even fewer (~13%) routinely implement this recommendation, even when receiving a financial incentive.5 These observations indicate that the main barrier to the effec tive implementation of interarm blood pres sure measurements in clinical practice is physicians’ inertia. A call for action against this inertia comes from the results of a new
NATURE REVIEWS | ENDOCRINOLOGY
study by Clark and colleagues,6 which high lights the prognostic relevance of interarm systolic blood pressure differences during the initial evaluation of patients with type 1 and type 2 diabetes mellitus. At recruitment, two pairs of blood pres sure measurements were performed in both arms by simultaneous activation of two automated sphygmomanometers and then repeated after swapping the cuffs. In a cross-sectional analysis performed in 727 patients with type 1 and type 2 diab etes mellitus and 285 individuals without dia betes mellitus, interarm systolic blood pres sure differences ≥10 mmHg were associated with an increased risk of peripheral arterial disease (OR 3.4, 95% CI 1.2–9.3) and dif ferences ≥15 mmHg were associated with an increased risk of diabetic retinopathy (OR 5.7, 95% CI 1.5–21.6) and chronic kidney disease (OR 7.0, 95% CI 1.7–29.8).6 These associations remained significant even after adjusting for age, sex, waist/ hip ratio, smoking status and systolic blood pressure. Over a median follow-up of 52 months, the risk of cardiovascularrelated mortality was markedly increased in patients with diabetes mellitus who had systolic interarm blood pressure differences ≥10 mmHg (HR 3.5, 95% CI 1.0–13.0) and ≥15 mmHg (HR 9.0, 95% CI 2.0–41.0).6 Remarkably, when sensitivity and speci ficity analyses were performed, interarm blood pressure differences determined from single pairs of sequentially performed blood pressure measurements were shown to correctly identify interarm systolic blood pressure differences ≥10 mmHg. This find ing highlights the value of a single pair of sequential blood pressure measurements that are easy to implement in clinical prac tice. This is of relevance if we consider that failure to identify interarm differences in blood pressure can lead to underestimating VOLUME 10 | JULY 2014 | 387
© 2014 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS the risk of hypertension and to subsequent undertreatment of patients.7 A strength of the present study 6 is the inclus ion of a large sample of patients with diabetes mellitus, and the adherence to a careful protocol for identifying inter arm blood pressure differences. Despite its gene ral interest, however, the study has several limitations. Firstly, although interarm blood pressure differences above predefined thresholds were compared in patients with diabetes mellitus and control individuals without diabetes mellitus, the association between interarm blood pres sure differe nces and vascular morbidity was only assessed in patients with diabetes mellitus. Indeed, as no data on the cardio vascular history of patients were available for individuals without diabetes mellitus, the effect of interarm blood pressure differ ences in patients with and without diabetes mellitus on risk of cardiovascular disease could not be comparat ively determined. As a consequence, whether interarm blood pressure differences are also a significant marker and predictor of cardiovascular disease in patients without diabetes mel litus could not be investigated. Secondly, the presence of vascular disease at baseline was identified on the basis of self-reported events obtained from patients’ medical history, which represents a possible source of bias. Thirdly, the study did not include quantification of markers of microvascular or macrovascular organ damage, such as microalbuminuria, indices of cardiac func tion and structure, and arterial stiffness; nor did it assess their association with interarm blood pressure differences. Data on carotid– femoral pulse wave velocity, an increase of which is regarded as a marker of vascular
organ damage, might have been of particu lar use. Fourthly, although in the present study no overall difference in the prevalence of hypertension was observed between par ticipants with or without interarm blood press ure differences above predefined thresholds, it would have nevertheless been important to correlate the degree of inter arm blood pressure difference with mean blood pressure values. Fifthly, this prospec tive study included only mortality data, even though the number of deaths occur ring during the follow-up period was small (cardiovascular mortality 2.3%; all-cause mortality 8.0%). Finally, the authors do not comment on their findings that both the cross-sectional association with cardio vascular damage and the prognostic value of interarm blood pressure differences with regard to mortality were only found for sys tolic blood pressure but, unexpectedly, not for diastolic blood pressure. In spite of the suggested prognostic implic ations of interarm blood pressure differences (Box 1), the pathophysiological mechanisms underlying these differences in patients with and without diabetes mellitus are not well understood. Increased blood pressure variability might be a contributing factor in the misdiagnosis of hypertension when interarm blood pressure differences are computed from sequential blood pres sure measurements, 8 as compared with simultaneous measurements. However, the persistence of significant (although less pro nounced than in sequential blood pressure measurements) interarm blood pressure differences when simultaneously measuring blood pressure in both arms indicates that short-term variability in blood pressure cannot entirely account for interarm blood
pressure differences. Although the uneven occurr ence of atherosclerotic stenotic lesions remains a plausible explanation of interarm blood pressure differences, addi tional mechanisms might also contribute, such as the uneven distribution of arterial tree stiffness and different wave reflec tions along the brachial arteries on the two sides. The different mechanisms of inter arm blood pressure differences should be explored in future studies. Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano, IRCCS, and Department of Health Sciences, University of Milan–Bicocca, Piazzale Brescia 20, Milan 20149, Italy (G.P.). Scientific Direction, Istituto Auxologico Italiano and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, University of Milan, Via F. Sforza 35, 20122 Milan, Italy (A.Z.). Correspondence to: G.P. [email protected] Acknowledgements The authors acknowledge the contributions made by Dr J. E. Ochoa and Dr P. Salvi in the preparation of this article. Competing interests The authors declare no competing interests. 1.
2.
3.
4.
Box 1 | Assessing interam blood pressure differences Why assess? ■■ To avoid underestimating actual blood pressure and misdiagnosing hypertension, in particular, in patients with diabetes mellitus, which can occur in the presence of interarm blood pressure differences if blood pressure readings are taken from only one arm ■■ To improve management of hypertension in patients with diabetes mellitus and other patients at high risk of cardiovascular disease, thereby reducing the cardiovascular risk associated with elevated blood pressure through accurate titration of drugs ■■ To improve prognostic stratification of patients with hypertension on the basis of the predictive value of interarm blood pressure differences
5.
6.
How to assess ■■ By measuring blood pressure in both arms during the first visit and then focusing on the arm with the highest blood pressure value when deciding how best to treat patients
7.
Methods for a reliable assessment ■■ Simultaneous blood pressure assessment from both arms is the gold standard for assessing interarm blood pressure differences ■■ A sequential pair of blood pressure measurements might be a simple and practical approach to more easily, yet reliably, quantify interarm blood pressure differences
8.
388 | JULY 2014 | VOLUME 10
[No authors listed] Hypertension in diabetes study (HDS): II. Increased risk of cardiovascular complications in hypertensive type 2 diabetic patients. J. Hypertens. 11, 319–325 (1993). O’Brien, E. et al. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J. Hypertens. 31, 1731–1768 (2013). Mancia, G. et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J. Hypertens. 31, 1281–1357 (2013). Clark, C. E., Taylor, R. S., Shore, A. C., Ukoumunne, O. C. & Campbell, J. L. Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and metaanalysis. Lancet 379, 905–914 (2012). Heneghan, C., Perera, R., Mant, D. & Glasziou, P. Hypertension guideline recommendations in general practice: awareness, agreement, adoption, and adherence. Br. J. Gen. Pract. 57, 948–952 (2007). Clark, C. E. et al. Interarm blood pressure difference in people with diabetes: measurement and vascular and mortality implications: a cohort study. Diabetes Care 37, 1613–1620 (2014). Clark, C. E., Greaves, C. J., Evans, P. H., Dickens, A. & Campbell, J. L. Inter-arm blood pressure difference in type 2 diabetes: a barrier to effective management? Br. J. Gen. Pract. 59, 428–432 (2009). Parati, G., Ochoa, J. E., Lombardi, C. Y. & Bilo, G. Assessment and management of blood-pressure variability. Nat. Rev. Cardiol. 10, 143–155 (2013).
www.nature.com/nrendo © 2014 Macmillan Publishers Limited. All rights reserved
DIABETES
Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850, USA (K.M.). Section of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, 1819 W. Polk Street, MC 640, Chicago, IL 60616, USA (A.B.S.). Correspondence to: K.M. [email protected]
Gianfranco Parati and Alberto Zanchetti
Acknowledgements The authors wish to acknowledge J. Loukissas of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA, who provided valuable insights during the writing of this article. Competing interests A.B.S. has served as an advisor and expert witness for a law firm dealing with radiation releases from the Hanford Nuclear Facility. K.M. declares no competing interests. 1.
National Research Council. Analysis of cancer risks in populations near nuclear facilities: phase 1 (The National Academies Press, 2012). 2. Bollaerts, K. et al. Thyroid cancer incidence in the vicinity of nuclear sites in Belgium, 2000–2008. Thyroid http://dx.doi.org/ 10.1089/thy.2013.0227. 3. Bouville, A., Linet, M. S., Hatch, M., Mabuchi, K. & Simon, S. L. Guidelines for exposure assessment in health risk studies following a nuclear reactor accident. Environ. Health Perspect. 122, 1–5 (2014). 4. Vandecasteele, C. M., Sonck, M. & Degueldre, D. Rejet accidentel d’iode‑131 par l’IRE sur le site de Fleurus: retour d’expérience de l’autorité de sûreté belge [French]. Radioprotection 46, 159–173 (2011). 5. United Nations Scientific Committee on the Effects of Radiation. Sources and effects of ionizing radiation. UNSCEAR 2000: Report to the general assembly with scientific annexes, Volume I [online], http://www.unscear.org/ unscear/en/publications/2000_1.html (2013). 6. Ron, E. et al. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat. Res. 141, 259–277 (1995). 7. Shakhatarin, V. V. et al. Iodine deficiency, radiation dose, and the risk of thyroid cancer among children and adolescents in the Bryansk region of Russia following the Chernobyl power station accident. Int. J. Epidemiol. 32, 584–591 (2003). 8. Davis, S. et al. Risk of thyroid cancer in the Bryask Oblast of the Russian Federation after the Chernobyl power plant station accident. Radiat. Res. 162, 241–248 (2004). 9. Davies, L. & Welch, H. G. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 295, 2164–2167 (2006). 10. Nose, T. & Oiwa, Y. Thyroid cancer cases increase among young people in Fukushima. The Asahi Shimbun [online], http:// ajw.asahi.com/article/0311disaster/ fukushima/AJ201402080047 (2014).
Measuring interarm blood pressure differences in diabetes Interarm differences in systolic blood pressure are associated with a significant risk of morbidity and mortality. A new study reports that these differences are frequently observed in patients with diabetes mellitus and recommends routine measurement of interarm blood pressure differences to improve diagnostic and prognostic stratification of these patients. Parati, G. & Zanchetti, A. Nat. Rev. Endocrinol. 10, 387–388 (2014); published online 3 June 2014; doi:10.1038/nrendo.2014.80
Patients with diabetes mellitus and ele vated blood pressure have a higher risk of cardiovascular disease than normotensive or hypertensive individuals without dia betes mellitus.1 The inaccurate assessment of blood pressure in primary care settings is a contributing factor in the increased cardiovascular risk observed in patients with diabetes mellitus. This increased risk is due not only to the intrinsic limitations of primary care blood pressure measure ments (such as, the inaccuracy of readings obtained under constraints of time, poten tial white coat effects, investigator bias and digit preference, and the inability of limited blood pressure measurements to faithfully reflect normal daily blood pressure), 2 but also to the frequent failure of practicing physicians to follow the guideline recom mendations for measuring blood pressure. One such recommendation consists of mea suring blood pressure in both arms at the first visit to detect possible interarm differ ences, and using the arm with the highest blood pressure value as the reference for making decisions about treatment.3 This recommendation is supported by the asso ciation between interarm differences in systolic blood pressure (≥10 mmHg) and vascular damage, cerebrovascular disease and increased risk of cardiovascular-related and all-cause mortality.4 However, although ~77% of primary care physicians are aware of guideline recommendations for mea suring blood pressure in both arms, only a minority of them (~30%) follow this advice, and even fewer (~13%) routinely implement this recommendation, even when receiving a financial incentive.5 These observations indicate that the main barrier to the effec tive implementation of interarm blood pres sure measurements in clinical practice is physicians’ inertia. A call for action against this inertia comes from the results of a new
NATURE REVIEWS | ENDOCRINOLOGY
study by Clark and colleagues,6 which high lights the prognostic relevance of interarm systolic blood pressure differences during the initial evaluation of patients with type 1 and type 2 diabetes mellitus. At recruitment, two pairs of blood pres sure measurements were performed in both arms by simultaneous activation of two automated sphygmomanometers and then repeated after swapping the cuffs. In a cross-sectional analysis performed in 727 patients with type 1 and type 2 diab etes mellitus and 285 individuals without dia betes mellitus, interarm systolic blood pres sure differences ≥10 mmHg were associated with an increased risk of peripheral arterial disease (OR 3.4, 95% CI 1.2–9.3) and dif ferences ≥15 mmHg were associated with an increased risk of diabetic retinopathy (OR 5.7, 95% CI 1.5–21.6) and chronic kidney disease (OR 7.0, 95% CI 1.7–29.8).6 These associations remained significant even after adjusting for age, sex, waist/ hip ratio, smoking status and systolic blood pressure. Over a median follow-up of 52 months, the risk of cardiovascularrelated mortality was markedly increased in patients with diabetes mellitus who had systolic interarm blood pressure differences ≥10 mmHg (HR 3.5, 95% CI 1.0–13.0) and ≥15 mmHg (HR 9.0, 95% CI 2.0–41.0).6 Remarkably, when sensitivity and speci ficity analyses were performed, interarm blood pressure differences determined from single pairs of sequentially performed blood pressure measurements were shown to correctly identify interarm systolic blood pressure differences ≥10 mmHg. This find ing highlights the value of a single pair of sequential blood pressure measurements that are easy to implement in clinical prac tice. This is of relevance if we consider that failure to identify interarm differences in blood pressure can lead to underestimating VOLUME 10 | JULY 2014 | 387
© 2014 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS the risk of hypertension and to subsequent undertreatment of patients.7 A strength of the present study 6 is the inclus ion of a large sample of patients with diabetes mellitus, and the adherence to a careful protocol for identifying inter arm blood pressure differences. Despite its gene ral interest, however, the study has several limitations. Firstly, although interarm blood pressure differences above predefined thresholds were compared in patients with diabetes mellitus and control individuals without diabetes mellitus, the association between interarm blood pres sure differe nces and vascular morbidity was only assessed in patients with diabetes mellitus. Indeed, as no data on the cardio vascular history of patients were available for individuals without diabetes mellitus, the effect of interarm blood pressure differ ences in patients with and without diabetes mellitus on risk of cardiovascular disease could not be comparat ively determined. As a consequence, whether interarm blood pressure differences are also a significant marker and predictor of cardiovascular disease in patients without diabetes mel litus could not be investigated. Secondly, the presence of vascular disease at baseline was identified on the basis of self-reported events obtained from patients’ medical history, which represents a possible source of bias. Thirdly, the study did not include quantification of markers of microvascular or macrovascular organ damage, such as microalbuminuria, indices of cardiac func tion and structure, and arterial stiffness; nor did it assess their association with interarm blood pressure differences. Data on carotid– femoral pulse wave velocity, an increase of which is regarded as a marker of vascular
organ damage, might have been of particu lar use. Fourthly, although in the present study no overall difference in the prevalence of hypertension was observed between par ticipants with or without interarm blood press ure differences above predefined thresholds, it would have nevertheless been important to correlate the degree of inter arm blood pressure difference with mean blood pressure values. Fifthly, this prospec tive study included only mortality data, even though the number of deaths occur ring during the follow-up period was small (cardiovascular mortality 2.3%; all-cause mortality 8.0%). Finally, the authors do not comment on their findings that both the cross-sectional association with cardio vascular damage and the prognostic value of interarm blood pressure differences with regard to mortality were only found for sys tolic blood pressure but, unexpectedly, not for diastolic blood pressure. In spite of the suggested prognostic implic ations of interarm blood pressure differences (Box 1), the pathophysiological mechanisms underlying these differences in patients with and without diabetes mellitus are not well understood. Increased blood pressure variability might be a contributing factor in the misdiagnosis of hypertension when interarm blood pressure differences are computed from sequential blood pres sure measurements, 8 as compared with simultaneous measurements. However, the persistence of significant (although less pro nounced than in sequential blood pressure measurements) interarm blood pressure differences when simultaneously measuring blood pressure in both arms indicates that short-term variability in blood pressure cannot entirely account for interarm blood
pressure differences. Although the uneven occurr ence of atherosclerotic stenotic lesions remains a plausible explanation of interarm blood pressure differences, addi tional mechanisms might also contribute, such as the uneven distribution of arterial tree stiffness and different wave reflec tions along the brachial arteries on the two sides. The different mechanisms of inter arm blood pressure differences should be explored in future studies. Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano, IRCCS, and Department of Health Sciences, University of Milan–Bicocca, Piazzale Brescia 20, Milan 20149, Italy (G.P.). Scientific Direction, Istituto Auxologico Italiano and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, University of Milan, Via F. Sforza 35, 20122 Milan, Italy (A.Z.). Correspondence to: G.P. [email protected] Acknowledgements The authors acknowledge the contributions made by Dr J. E. Ochoa and Dr P. Salvi in the preparation of this article. Competing interests The authors declare no competing interests. 1.
2.
3.
4.
Box 1 | Assessing interam blood pressure differences Why assess? ■■ To avoid underestimating actual blood pressure and misdiagnosing hypertension, in particular, in patients with diabetes mellitus, which can occur in the presence of interarm blood pressure differences if blood pressure readings are taken from only one arm ■■ To improve management of hypertension in patients with diabetes mellitus and other patients at high risk of cardiovascular disease, thereby reducing the cardiovascular risk associated with elevated blood pressure through accurate titration of drugs ■■ To improve prognostic stratification of patients with hypertension on the basis of the predictive value of interarm blood pressure differences
5.
6.
How to assess ■■ By measuring blood pressure in both arms during the first visit and then focusing on the arm with the highest blood pressure value when deciding how best to treat patients
7.
Methods for a reliable assessment ■■ Simultaneous blood pressure assessment from both arms is the gold standard for assessing interarm blood pressure differences ■■ A sequential pair of blood pressure measurements might be a simple and practical approach to more easily, yet reliably, quantify interarm blood pressure differences
8.
388 | JULY 2014 | VOLUME 10
[No authors listed] Hypertension in diabetes study (HDS): II. Increased risk of cardiovascular complications in hypertensive type 2 diabetic patients. J. Hypertens. 11, 319–325 (1993). O’Brien, E. et al. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J. Hypertens. 31, 1731–1768 (2013). Mancia, G. et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J. Hypertens. 31, 1281–1357 (2013). Clark, C. E., Taylor, R. S., Shore, A. C., Ukoumunne, O. C. & Campbell, J. L. Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and metaanalysis. Lancet 379, 905–914 (2012). Heneghan, C., Perera, R., Mant, D. & Glasziou, P. Hypertension guideline recommendations in general practice: awareness, agreement, adoption, and adherence. Br. J. Gen. Pract. 57, 948–952 (2007). Clark, C. E. et al. Interarm blood pressure difference in people with diabetes: measurement and vascular and mortality implications: a cohort study. Diabetes Care 37, 1613–1620 (2014). Clark, C. E., Greaves, C. J., Evans, P. H., Dickens, A. & Campbell, J. L. Inter-arm blood pressure difference in type 2 diabetes: a barrier to effective management? Br. J. Gen. Pract. 59, 428–432 (2009). Parati, G., Ochoa, J. E., Lombardi, C. Y. & Bilo, G. Assessment and management of blood-pressure variability. Nat. Rev. Cardiol. 10, 143–155 (2013).
www.nature.com/nrendo © 2014 Macmillan Publishers Limited. All rights reserved
