Why Is Blood Pressure So Hard to Control in Patients With Type 2 Diabetes?

Abstract

Resistance to antihypertensive drugs is common in hypertensive patients with type 2 diabetes. This is unfortunate because hypertension is one of the most important risk factors for development of cardiovascular events, and the goal blood pressure level is set lower in diabetic subjects than in nondiabetic subjects. Previous outcome trials in diabetic subjects have mainly focused on end points such as microalbuminuria or the incidence of cardiovascular events rather than on reduction of blood pressure; some reports, however, have suggested mechanisms for the drug resistance. These include several clinical conditions known to be associated with difficulty in reducing blood pressure specifically in diabetes mellitus: change in the renin-angiotensin system and chymase, volume overload, central sympathetic hyperactivity, sleep apnea, secondary hypertension, pseudoresistance (white coat hypertension), and poor compliance related to subclinical depression. In this review, the authors focus on the mechanisms of resistance to antihypertensive therapy (particularly for monotherapy with either angiotensin-converting enzyme inhibitors or angiotensin II antagonists) in the treatment of diabetic hypertension.

Leader-4

“…The predictors of nonachievement of BP targets in our analyses were broadly similar, independently of the target figures used. The observation that BP control was markedly better in the United States than in Europe in the large samples of patients with T2DM and high cardiovascular risk recruited into the LEADER trial prompts us to reflect on the potential public health effects of the recent global (European-led) relaxation of BP targets in terms of hypertension-related cardiovascular outcomes, particularly given that targets are infrequently achieved and BP lowering using currently available pharmacological agents is well established to reduce rates of mortality and other complications [ 41 ]. The SPRINT trial has recently highlighted the benefits of BP-lowering in nondiabetic individuals and hence rekindled enthusiasm for more intensive BP targets in diabetes [ 42 ].…”

“…It is clear from the present analysis that BP targets are too infrequently achieved in many individuals with T2DM. Many mechanisms for resistance to therapy have been identified and reviewed, including higher baseline BP because of obesity, activation of the sympathetic nervous system, changes in central hemodynamics [ 43 ], volume overload, and renin–angiotensin system activation [ 41 ]. Glucose-lowering therapies that also possess BP-lowering effects may therefore have an attractive profile from a CVD prevention perspective, as demonstrated by a reduction in cardiovascular death with the SGLT-2 inhibitor with empagliflozin as recently reported in the EMPA-REG trial [ 44 ].…”

Ambulatory Blood Pressure Monitoring in Diabetes and Obesity—A Review

“…In combination with the findings of masked hypertension in diabetes (described below) [12], these results lead us to advocate that all diabetic subjects should undergo ABPM at least once regardless of the presence of hypertension. Even in cases of resistant hypertension in diabetes, pseudoresistance, that is, apparent hypertension in the clinic but normal BP outside the clinic, is sometimes observed due to the white-coat effect [13]. …”

Systolic Blood Pressure Response in SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD (Action to Control Cardiovascular Risk in Diabetes): A Possible Explanation for Discordant Trial Results

“…In addition, SPRINT was singularly a blood pressure trial, whereas ACCORD had 3 components including the diabetes trial,10 a lipid trial, and a blood pressure trial, which may have had some impact on SBP responses. It is possible that the difference in the SBP distribution was also related to underlying diabetes mellitus, perhaps because controlling blood pressure in patients with diabetes mellitus may be more difficult and slower 21, 22…”