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Practical Diabetes Care, 3rd Ed., Excerpt #26: Hypertension Part 1 of 5

David Levy, MD, FRCP     

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Introduction

Despite more clinical trials than any other aspect of diabetes, many questions still remain about hypertension. Treatment targets continued to fall after UKPDS (1998), but even in contemporary trials with the most stringent treat-to-target protocols they are rarely achieved (see Chapter 8). Because antihypertensive agents, like statins, have log-linear dose–response characteristics, progressive blood pressure lowering requires increasing intensity of treatment, with attendant risks of side-effects, expense and most importantly the possibility of limited improvement in long-term outcomes. Establishing an evidence-based target was therefore important. The hypertension arm of ACCORD (2010) established in the early 2000s was still able to justify randomizing type 2 patients to systolic targets of 140 or 120 mmHg [1]. The to some surprising outcome was that in patients with established diabetes and risk factors for, or evidence of, macrovascular disease, maintaining systolic blood pressure (SBP) at about 120 mmHg conferred no macrovascular advantage compared with a less intensive achieved level of about 133 mmHg, apart from the expected reduction in stroke outcome…

Even more counterintuitive was the finding that intensive lowering of blood pressure did not reduce progression of retinopathy [2]. However, the baseline blood pressure (139/76 mmHg) was already relatively well-controlled hypertension, not far from existing treatment targets, and lower than the achieved level in the intensively controlled group of UKPDS (144/82 mmHg). Similar to the ACCORD glycemic study, it appears we have reached the practical limits to significant improvements in outcomes using conventional treatments especially in patients with established vascular disease, contrasting with the epidemiological evidence in mostly healthy populations. The striking exception remains proteinuric patients and as in the glycemic studies and the UKPDS findings, compared with the studies in longer-duration diabetes, we are left with the question of whether patients with more recent onset type 2 diabetes and presumably less vascular disease might benefit from more stringent blood pressure control.

Nevertheless, intensive lowering of blood pressure from UKPDS-like levels (baseline 160/94 mmHg) has consistently dramatic beneficial effects in diabetes. In the UKPDS, microvascular complications and stroke were both reduced by about 40%, and heart failure by more than 50%, though there was no significant effect on myocardial infarction. However, in contrast to the well-established legacy effects of glycemia (and multimodal treatment in Steno-2), the 10-year UKPDS follow-up found that the vas- cular benefit of intensive blood pressure lowering was abolished as soon as control was relaxed. Despite the continuing controversies, there is agreement on several major areas (Box 11.1).

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Pathophysiologically, hypertension comprises elements of vasoconstriction (probably mediated by renin) and volume (salt) overload, or in many cases both. The rediscovery of this basic concept is important for the treatment of hypertension, in particular resistant hypertension, a common problem in diabetes. Most patients therefore require a drug or combination of drugs that address salt overload (i.e. a diuretic), which increase renin, and a drug or drugs that block the renin–angiotensin–aldosterone system. Low-renin hypertension is common in diabetes (renin levels decrease with age, and are characteristically low in black subjects). In future, measurement of plasma renin levels may help diagnose and guide treatment of resistant hypertension [3].

Type 1 diabetes
At diagnosis, blood pressure is no higher than that of non-diabetic people. In the absence of microalbuminuria, blood pressure changes with time in a similar fashion to that of non-diabetic people, but anticipating it by some 15–20 years. SBP is higher at all ages, while diastolic blood pressure (DBP) starts to fall earlier than in non-diabetic subjects; the result is a strikingly higher pulse pressure at all ages and durations of diabetes, indicating accelerated arterial ageing and stiffening. For example, about 15% of 18–24 year old Finns were hypertensive (?: 140/?: 90 mmHg), increasing to about 20–25% in the 25–40 year old group. (Fig. 11.1) Similar rates are found across Europe (EURODIAB study). By their early thirties, type 1 subjects have higher pulse pressures at any level of albuminuria than young people without diabetes [4]. Actively look for hypertension, especially if there is no microalbuminuria: blood pressure, especially during the night, starts to rise at the same time, or even before, microalbuminuria occurs. Blood pressure can also rise in intensively treated patients who gain weight, together with some other features of the insulin resistance syndrome. The concept of pre-hypertension (SBP 120–139 mmHg, DBP 80–89 mmHg) is especially useful here as an indicator of likely progression to true hypertension, with emphasis on lifestyle interventions, as there is no evidence yet for the benefit of pharmacological treatment.

Once microalbuminuria is established, then angiotensin blocker treatment is mandatory, regardless of blood pressure (see Chapter 8).

Blood pressure should be monitored carefully in young people under 18 with diabetes, most of whom will currently have type 1 diabetes, though this is likely to change. However, it is important to use age-, gender- and height-related measurements (see Numbers, Conversions and Tables). Pre-hypertension is defined as a blood pressure between the 90th and 95th percentile, which should be managed with intensive lifestyle input; in patients with persistent measurements above the 95th percentile medication can be considered, especially if there is microalbuminuria, but this requires detailed and careful discussion.

Type 2 diabetes
In striking contrast with type 1 diabetes, about three-quarters of type 2 patients are definitely hypertensive (?: 140/?: 90 mmHg) at diagnosis, and nearly all macroalbuminuric patients are hypertensive. Black patients have an especially high prevalence of hypertension, hypertensive nephrosclerosis and LVH, an independent predictor of coronary death (Fig. 11.2). Isolated systolic hypertension (SBP > 140, DBP < 90 mmHg), again with a major contribution from increased arterial stiffness, is common, as is atherosclerotic renal artery stenosis (see Chapter 8).

References:

  1. Cushman WC, Evans GW, Byington RP et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. ACCORD Study Group. N Engl J Med 2010; 362:1575–85. PMID: 20228401.
  2. Chew EY, Ambrosius WT, Davis MD et al. ACCORD Study Group and ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233–44. PMID: 20587587.
  3. Brown MJ. Renin: friend or foe? Heart 2007;93:1026–33. PMID: 17488768.
  4. Rönnback M, Fagerudd J, Forsblum C, Pettersson-Fernholm K, Reunanen A, Groop PH. Altered age-related blood pressure pattern in type 1 diabetes. Finnish Diabetic Nephropathy (FinnDiane) Study Group. Circulation 2004;110:1076–82. PMID: 15326070.
  5. Shimbo D, Pickering TG, Spruill TM, Abraham D, Schwartz JE, Gerin W. Relative utility of home, ambulatory, and office blood pressures in the prediction of end-organ damage. Am J Hypertens 2007;20:476–82. PMID: 17485006.
  6. Verberk WJ, Kroon AA, Lenders JW et al. Self-measurement of blood pressure at home reduces the need for antihypertensive drugs: a randomized controlled trial. Home Versus Office Measurement, Reduction of Unnecessary Treatment Study Investigators. Hypertension 2007;50:1019–25. PMID: 17938383.
  7. Spence JD. White-coat hypertension is hypertension. Hypertension 2008;51:1272. PMID: 18378857.
  8. Kikuya M, Hansen TW, Thijs L et al. Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk. IDACO Investigators. Blood Press Monit 2007;12:393–5. PMID: 18277319.
  9. Sacks FM, Campos H. Dietary therapy in hypertension. N Engl J Med 2010;362:2102–12. PMID: 20519681.
  10. Cook NR, Cutler JA, Obarzanek E et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP). Br Med J 2007;334:885–8. PMID: 17449506.
  11. Tejada T, Fornoni A, Lenz O, Materson BJ. Nonpharmacologic therapy for hypertension: does it really work? Curr Cardiol Rep 2006;8:418–24. PMID: 17059793.
  12. Zillich AJ, Garg J, Basu S, Bakris GL, Carter BL. Thiazide diuretics, potassium, and the development of diabetes: a quantitative review. Hypertension 2006;48:219–24. PMID: 16801488.
  13. Jamerson K, Weber MA, Bakris GL et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. ACCOMPLISH Trial Investigators. N Engl J Med 2008;359:2417–28. PMID: 19052124.
  14. Yusuf S, Teo KK, Pogue J et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. ONTARGET Investigators. N Engl J Med 2008;358:1547– 59. PMID: 18378520.
  15. Wright JT Jr, Bakris G, Greene T et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. African American Study of Kidney Disease and Hypertension Study Group. JAMA 2002;288:2421–31. PMID: 12435255.
  16. Nissen SE, Tuzcu M, Libby P et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA 2004;292:2217–25. PMID: 15536108.
  17. Bakris GL, Fonseca K, Katholi RE et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA 2004;292:2227–36. PMID: 15536109.
  18. Ernst ME, Moser M. Use of diuretics in patients with hypertension. N Engl J Med 2009;361:2153–64. PMID: 19940300.
  19. Vrijens B, Vincze G, Kristanto P, Urquhart J, Burnier M. Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories. Br Med J 2008;336:1114–17. PMID: 18480115.
  20. Funder JW, Carey RM, Fardella C et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2008;93:3266–81. PMID: 18552288.

 

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David Levy, MD, FRCP, Consultant Physician, Gillian Hanson Centre, Whipps Cross University Hospital; Honorary Senior Lecturer
Queen Mary University of London London, UK

This edition first published 2011, © 2011 by David Levy. 1st edition 1998 (Greenwich Medical Media/Cambridge University Press) 2nd edition 2006 (Altman Publications)