I read with interest the paper by Juraschek SP, et al. 1 The authors in their sub‐analysis of Systolic Blood Pressure Intervention Trial (SPRINT) make several useful statements regarding the cardiovascular benefits of aggressive control of systolic blood pressure (SBP) of <120 mm Hg compared to standard therapy of <140 mm Hg. However, they make a questionable statement that there is “no need to down titrate the treatment in ‘asymptomatic’ patients with drug‐induced orthostatic hypotension (OH).” Orthostatic hypotension has been defined by the authors as a decrease in SBP and diastolic blood pressure (DBP) of ≥20 and ≥10 mm Hg upon assuming the upright posture, respectively. However, “in their asymptomatic group” there were several patients with OH and “non myocardial infarction (MI) acute coronary syndrome (ACS),” HR 2.56 (95% CI 1.04‐6.31) in the aggressive treatment vs 0.35 (95% CI 0.05‐2.73) in the standard treatment group (p interaction 0.03). The authors state that the interaction between groups became no significant after adjustments, although it was still higher than standard therapy. It is not clear what the adjustments did since both groups had very similar clinical and metabolic profiles. The ACS is not a benign condition, but an acute angina pain syndrome that frequently leads to MI and death and deserves prompt attention. I think the authors deemphasized the importance of ACS, which commonly occurs in patients with low DBP and is due to a J curve effect. 2 There are several studies that have demonstrated serious adverse cardiovascular and cerebrovascular effects of OH 3 , 4 , 5 , 6 and are summarized in Table 1. All these studies have demonstrated that OH was associated with increased incidence of stroke, all‐cause mortality, coronary heart disease, heart failure (HF), and several other cardiovascular events. Orthostatic hypotension should not be taken lightly, because it is associated with adverse cardiovascular events, especially in older patients in whom it has an incidence of 22.2%. 7 The statement that the aggressive SBP control decreased the primary composite outcome (MI, other acute coronary syndromes, stroke, HF, or cardiovascular death) is a statistical quirk, because it did not decrease the individual components of the primary composite outcome, such as MI or stroke with the exception of HF. It should also be realized that aggressive treatment of SBP in SPRINT resulted in serious clinical and metabolic adverse cardiovascular events in 38.3% in the aggressive treatment group vs 37.1% in the standard treatment group that included hypotension, syncope, electrolyte abnormalities (hyperkalemia), and acute kidney injury or acute renal failure. 8 Low DBP disturbs the autoregulation of coronary blood flow and increases the likelihood of angina and MI, since the myocardium is perfused during the diastolic phase of the cardiac cycle and this could have accounted for the ACS described by the authors. 2 Therefore, treatment associated OH, even in asymptomatic patients should be followed with down titration of treatment, especially in older persons with underlined cardiovascular disease to a DBP of 70‐80 mm Hg, since this pressure has been safe and prevents the incidence of adverse cardiovascular events. 9 Finally, it should be stated that the matter of overall effectiveness and safety of aggressive BP control has not been settled as yet. The SPRINT has been an important and provocative trial, but it has not been doublicated by another similar study. The ACCORD trial, 10 which had also a similar aggressive SBP control protocol, included only diabetic hypertensive patients, and this study did not show a significant reduction in MI with the exception of stroke. Therefore, further studies are needed to verify the findings of SPRINT.
Table 1.
Serious Adverse Cardiovascular Effects of Orthostatic Hypotension
| Author | Study | Patients | Age | SOH | Event | Statistical |
|---|---|---|---|---|---|---|
| (type) | (no) | (years) | (mm Hg) | (kind) | (significance) | |
| Federowski 3 | Prosp | 8,788 | 52 | (≥20/) | Stroke | HR 1.53/1.48 |
| CEP | HR 1.24/1.21 | |||||
| Xin 4 , a | Rev/Meta | 56,125 | 46‐86 | (≥20) | ACM | RR 1.40 |
| Ricci 5 , a | Rev/Meta | 121,913 | NA | (≥20) | ACM, CHD | RR 1.50, 1.41 |
| HF | RR 2.25 | |||||
| Khan 6 | RCT | 9,361 | 67 ± 9.4 | (DOH < 55) | CVE | HR 1.52 |
Abbreviations: ACM, all‐cause mortality; CEP, composite end point; CVE, cardiovascular events; HR, hazard ratios; NA, not available; Prosp, prospective study; Rev/Meta;review/meta‐analysis; RR, relative risk; SOH‐DOH, Systolic‐diastolic orthostatic hypotension.
These studies do not report either SOH or DOH and assumed to be SOH.
CONFLICT OF INTEREST
The author declares no conflict of interest and that no funds were received for the preparation of the manuscript.
Chrysant SG. Orthostatic hypotension and cardiovascular outcomes: Should we be concerned?. J Clin Hypertens. 2020;22:2161–2162. 10.1111/jch.14026
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