Orthostatic Hypotension in Diabetics in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Blood Pressure Trial.

Orthostatic hypotension (OH) is a reduction of ≥20 mm Hg in systolic blood pressure (SBP) or a reduction of ≥10 mm Hg in diastolic blood pressure within 3 minutes of standing. OH may be caused by an excessive decrease in blood volume when a person is standing or from inadequate compensation for the reduction in cardiac preload associated with standing because of deficient stimulation of cardiopulmonary, aortic, and carotid baroreceptors, which reflexly increase sympathetic activity and decrease parasympathetic activity. OH may be associated with advanced age, diabetes mellitus, hypertension, neurological disorders, and medications such as antihypertensive drugs, antidepressants, anti-parkinsonian drugs, antipsychotics, nitrates, alcohol, cardiovascular disorders, endocrine disorders, dehydration, anemia, bedrest/deconditioning, and other disorders. All older individuals taking antihypertensive drugs should routinely have blood pressure (BP) measured in the sitting position and within 3 minutes of standing. BP should not be measured immediately after eating to avoid postprandial hypotension being confused with OH. Both of these disorders may coexist. Postprandial hypotension is also associated with falls, syncope, coronary events, stroke, and all-cause mortality at long-term follow-up. OH may cause postural instability, falls, and syncope. OH is also associated with an increased incidence of all-cause mortality, coronary events, heart failure, and stroke. The prevalence of OH in 12 433 individuals in the Atherosclerosis Risk in Communities study was 4.9%. At 6-year mean follow-up, individuals with OH had a 3.49× increased risk of coronary heart disease. After controlling for age, ethnicity, sex, comorbid conditions, and cardiovascular risk factors, the hazard ratio for coronary heart disease was increased by 1.85×. A meta-analysis of 13 prospective studies included 121 913 individuals. At 5-year median follow-up of 65 174 individuals, OH increased all-cause mortality by 1.50×. At 6.4-year median follow-up of 49 512 individuals, OH increased coronary heart disease by 1.41×. At 6.8 to 24-year mean follow-up of 50 096 individuals, OH increased heart failure by 2.25×. At 6.8-year median follow-up of 58 300 individuals, OH increased stroke by 1.64×. The ACCORD BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial randomized 4733 diabetics, mean age 62.1 years, to lower SBP to <120 mm Hg or to <140 mm Hg. After 1 year, the SBP was 119.3 mm Hg with intensive BP control (IBPC) versus 133.5 mm Hg with standard therapy. The annual rates of the primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were 1.87% with IBPC versus 2.09% with standard therapy (a 12% insignificant reduction). The annual rates of stroke (a prespecified secondary outcome) were 0.32% with IBPC versus 0.53% with standard therapy (a 41% reduction). A post hoc analysis of data from ACCORD BP showed that the primary cardiovascular disease outcome was 26% less in individuals randomized to IBPC and standard glycemia goals than in individuals randomized to standard therapy and standard glycemia goals. In addition, an SBP of <120 mm Hg in ACCORD BP was associated with a 39% reduced risk of electrocardiographic left ventricular hypertrophy. Reduction of left ventricular hypertrophy has been found to reduce cardiovascular events. The excellent study by Fleg et al investigated the prevalence, incidence, and prognostic significance of OH in the ACCORD BP trial. Orhostatic blood pressure measurements were made in 1321 individuals at baseline, in 2625 individuals at 12 months, in 3702 individuals at 48 months, and in 926 individuals at all 3 visits. The smaller number of orthostatic blood pressure measurements at baseline and at 12 months was because of this investigation not beginning until 44 months after the ACCORD BP trial began. The prevalence of OH at a specific visit was defined based on the occurrence of consensus OH at that visit, regardless of whether OH had been previously diagnosed. The incidence of OH at a specific follow-up visit was defined as the occurrence of consensus OH at that visit in individuals examined previously who had not been shown to have OH. The prevalence of OH was 17.8% at baseline, 10.4% at 12 months, 12.8% at 48 months, and 20% at ≥1 visit. At baseline, the prevalence of OH was 19.3% in individuals treated with IBPC versus 16.1% in those treated with standard therapy (P not significant). At 12 months, the prevalence of OH was 9.5% in individuals treated with IBPC versus 11.4% in those treated with standard therapy (P not significant). At 48 months, the prevalence of OH was 12.2% in individuals treated with IBPC versus 13.5% in those treated with standard therapy (P not The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. From the Cardiology Division, Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla. Correspondence to Wilbert S. Aronow, Cardiology Division, New York Medical College, Macy Pavilion, Room 141, Valhalla, NY 10595. E-mail [email protected] Orthostatic Hypotension in Diabetics in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Blood Pressure Trial