hypertension; blood pressure; diabetes mellitus; cardiovascular events
Hypertension is a common comorbidity in older persons with diabetes mellitus, and its prevalence increases with advancing age . Hypertension and diabetes mellitus are both major independent risk factors for cardiovascular events in older persons [2-6]. Left ventricular hypertrophy associated with hypertension increases cardiovascular events . Reduction of electrocardiographic left ventricular hypertrophy by antihypertensive treatment of isolated systolic hypertension has been demonstrated to reduce cardiovascular events and mortality [7,8].
Hypertension guidelines since 2011 have recommended a blood pressure target goal of less than 140/90 mm Hg in diabetics younger than 80 years and of less than 150/90 mm Hg in diabetics aged 80 years and older [2,9-14]. The 2014 American Society of Hypertension/International Society of Hypertension guidelines recommended considering lowering the blood pressure to less than 140/90 mm Hg in elderly diabetics aged 80 years and older . We reported data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study . This study included 4,181 persons aged 55-64 years, 3,737 persons aged 65-74 years, and 1,839 patients aged 75 years and older (mean age 79.3 years) on antihypertensive drug therapy. Data from this study also support a blood pressure goal of less than 140/90 mm Hg in elderly persons .
The new guidelines for the management of patients with hypertension will be strongly influenced by the results from the Systolic Blood Pressure Intervention Trial (SPRINT) . SPRINT randomized 9,361 patients with a systolic blood pressure of 130-180 mm Hg and an increased cardiovascular risk but without diabetes mellitus, history of stroke, symptomatic heart failure within the past 6 months, a left ventricular ejection fraction of less than 35%, and an estimated glomerular filtration rate less than 20 ml/min/1.73 m2 to a systolic blood pressure target of less than 120 mm Hg or to a systolic blood pressure target of less than 140 mm Hg . The patients were aged 50 years and older with a mean age of 67.9 years. Of the 9,361 patients, 2,636 (28.2%) were aged 75 years and older, 3,332 (35.6%) were women, 5,399 (57.7%) were non-Hispanic white, 2,947 (31.5%) were black, and 984 (10.6%) were Hispanic. Cardiovascular disease was present in 1,877 patients (20.1%), and the Framingham 10-year cardiovascular disease risk score was ≥15% in 5, 737 patients (61.3%).
At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive treatment group and 136.2 mm Hg in the standard treatment group. The intervention was stopped early after a median follow-up of 3.26 years .
The primary composite outcome was myocardial infarction, other acute coronary syndrome, stroke, heart failure, or death from cardiovascular causes and was reduced 25%(p<0.001) by intensive blood pressure treatment . All-cause mortality was reduced 27%( p=0.003) by intensive blood pressure treatment. Heart failure was reduced 38% ( p=0.002) by intensive blood pressure treatment. Death from cardiovascular causes was reduced 43%(p=0.005) ) by intensive blood pressure treatment. The primary composite outcome or death was reduced 22% ( p <0.001) ) by intensive blood pressure treatment. Intensive blood pressure treatment insignificantly decreased myocardial infarction by 17%, caused the same incidence of other acute coronary syndrome, and insignificantly reduced stroke by 11%. Intensive blood pressure treatment significantly reduced the primary outcome 33% in patients aged 75 years and older and significantly reduced the primary outcome 20% in patients aged 50 to 74 years .
Serious adverse events were similar in both treatment groups . However, intensive blood pressure treatment caused more hypotension (2.4% versus 1.4%, p =0.001), more syncope (2.3% versus 1.7%, p=0.05), more electrolyte abnormality (3.1% versus 2.3%, p=0.02), and more acute kidney injury or acute renal failure (4.1% versus 2.5%, p<0.001). The incidence of bradycardia, injurious falls, and orthostatic hypotension with dizziness was similar in both treatment groups.
The new hypertension guidelines will have to answer on the basis of expert medical opinion many questions not answered by SPRINT. One of these questions is what should be the target systolic blood pressure in diabetics?
In The action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD BP) trial, reducing the systolic blood pressure to less than 120 mm Hg in 4,733 persons insignificantly lowered the composite primary outcome of myocardial infarction, stroke, or cardiovascular death 12% but significantly lowered the incidence of stroke (a prespecified secondary outcome) 41% (p=0.01 . The sample size was much larger in SPRINT (9,361 persons) than in ACCORD BP (4,733 persons), and there were important methodological differences between both trials [16-20]. The patients in SPRINT were older (mean age 67.9 years) than in ACCORD BP (mean age 62.2 years). The patients in ACCORD BP were at lower risk than the patients in SPRINT. Patients with dyslipidemia were assigned to the lipid arm and excluded from the blood pressure arm in ACCORD BP. Patients with a serum creatinine above 1.5 mg/dL were also excluded from ACCORD BP. In addition, the use of diuretics was different in these trials. ACCORD BP often used hydrochlorothiazide, whereas SPRINT primarily used chlorthalidone (my preference) .
A post-hoc analysis of the results from ACCORD BP also showed that the primary cardiovascular disease outcome was 26% lower in patients randomized to intensive blood pressure treatment and standard glycemia goals than in patients randomized to standard blood pressure treatment and standard glycemia goals . In addition, targeting a systolic blood pressure of less than 120 mm Hg in ACCORD BP was associated with a 39% lower risk of electrocardiographic left ventricular hypertrophy (p=0.008) .
In conclusion, a randomized clinical trial using a similar number of patients enrolled in SPRINT and the design used in SPRINT needs to be performed in diabetics with hypertension to determine whether the target systolic blood pressure in this population should be reduced to less than 120 mm Hg or to less than 140 mm Hg. On the basis of the available data, I recommend reducing the systolic blood pressure in diabetics at increased cardiovascular risk to less than 120 mm Hg. However, because of a higher incidence of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure in patients treated to a systolic blood pressure target goal less than 120 mm Hg, these patients will require more intensive monitoring for serious adverse events with an increased cost of care.
- Aronow WS (2008) Hypertension and the older diabetic. Clin Geriatr Med 24: 489-450. [Crossref]
- Aronow WS, Fleg JL, Pepine CJ, et al. (2011) CF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus. J Am Coll Cardiol 2037-2114.
- Aronow WS, Ahn C, Kronzon I, Koenigsberg M (1991) Congestive heart failure, coronary events and atherothrombotic brain infarction in elderly blacks and whites with systemic hypertension and with and without echocardiographic and electrocardiographic evidence of left ventricular hypertrophy. Am J Cardiol 67: 295-299. [Crossref]
- Aronow WS, Ahn C (1996) Risk factors for new coronary events in a large cohort of very elderly patients with and without coronary artery disease. Am J Cardiol 77: 864- 866 [Crossref]
- Aronow WS, Ahn C, Gutstein H (1996) Risk factors for new atherothrombotic brain infarction in 664 older men and , 488 older women. Am J Cardiol 77: 1381-1383. [Crossref]
- Aronow WS, Sales FF, Etienne F, Lee NH (1988) Prevalence of peripheral arterial disease and its correlation with risk factors for peripheral arterial disease in elderly patients in a long-term health care facility. Am J Cardiol 62: 644- 646. [Crossref]
- Larstorp AC, Okin PM, Devereux RB, Olsen MH, Ibsen H, et al. (2011) Changes in electrocardiographic left ventricular hypertrophy and risk of major cardiovascular events in isolated systolic hypertension: the LIFE study. J Hum Hypertens 25: 178-185. [Crossref]
- Larstorp AC, Okin PM, Devereux RB, Olsen MH, Ibsen H, et al. (2012) Regression of ECG-LVH is associated with lower risk of new-onset heart failure and mortality in patients with isolated systolic hypertension; The LIFE study. Am J Hypertens 25: 1101- 1109. [Crossref]
- Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, 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). Eur Heart J 34: 2159-2219. [Crossref]
- James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, et al. (2014) 2014 evidence-based guideline for the management of high blood pressure in adults. Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA 311: 507-520. [Crossref]
- Hackam DG, Quinn RR, Ravani P, Rabi DM, Dasgupta K, et al. (2013) The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol 29: 528-542. [Crossref]
- National Institute for Health and Clinical Excellence (2011) Hypertension: clinical management of primary hypertension in adults. London: National Institute for Health and Clinical Excellence. [Crossref]
- Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, et al. (2014) Clinical practice guidelines for the management of hypertension in the community. A statement by the American Society of Hypertension and the International Society of Hypertension. J Hypertens 16: 14-26. [Crossref]
- Rosendorff C, Lackland DT, Allison M, Aronow WS, et al. (2015) AHA/ACC/ASH scientific statement. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. J Am Coll Cardiol 651998-2038.
- Banach M, Bromfield S, Howard G, Howard VJ, Zanchetti A, et al. (2014) Association of systolic blood pressure levels with cardiovascular events and all-cause mortality among older adults taking antihypertensive medication. Int J Cardiol 176: 219-226. [Crossref]
- SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, et al. (2015) A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 373: 2103-2116. [Crossref]
- ACCORD Study Group, Cushman WC, Evans GW, Byington RP, Goff DC Jr, et al. (2010) Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 362: 1575-1585. [Crossref]
- Cushman WC, Whelton PK, Fine LJ, Wright JT Jr, Reboussin DM, et al. (2016) SPRINT Trial Results: Latest News in Hypertension Management. Hypertension 67: 263-265. [Crossref]
- Margolis KL, O'Connor PJ, Morgan TM, Buse JB, Cohen RM, et al. (2014) Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial. Diabetes Care 37: 1721-1728. [Crossref]
- Jones DW, Weatherly L, Hall JE (2016) SPRINT: What Remains Unanswered and Where Do We Go From Here? Hypertension 67: 261-262 [Crossref]
- Soliman EZ, Byington RP, Bigger JT, Evans G, Okin PM, et al. (2015) Effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with diabetes mellitus: Action to Control Cardiovascular Risk in Diabetes Blood Pressure Trial. Hypertension 66: 1123-1129. [Crossref]