Short‐term blood pressure variability in acute coronary syndrome

Blood pressure (BP) variability is a dynamic phenomenon including short‐, medium‐, and long‐term fluctuations as a result of complex interactions between behavioral, humoral, and neural central or reflex influences. The magnitude of such fluctuations is dependent on several variables including BP status (ie, normotension vs hypertension), changes in blood plasma volume, preload and afterload variations, respiratory cycles, use of antihypertensive medications, and the individual response to a variety of daily life stimuli such as physical activity, mental stress, duration/quality of sleep, smoking, alcohol consumption, seasonal variations in outdoor temperature, and other physiological and pathological factors.1

Abnormal BP variability has been linked in many, but not all, studies to an increase in cardiovascular risk, cardiac and extracardiac target organ damage, and death in different clinical settings, although most of the information comes from investigations conducted in hypertensive cohorts.2, 3 So far, the relationship of exaggerated BP variability with a worse cardiovascular prognosis in particular groups of patients, such as those with acute coronary syndrome (ACS), remains largely unexplored.

In this issue of the Journal, the study by Hassan and colleagues4 provides a new piece of information by showing that short‐term BP variability, as assessed by ambulatory BP monitoring (ABPM), is an independent predictor of major adverse cardiovascular events (MACEs; eg, death, myocardial reinfarction, stroke, heart failure, hypertensive crisis, life‐threatening arrhythmia) in both normotensive and hypertensive hospitalized patients with ACS.

Before commenting on the strengths and limitations of this study, some general considerations on available evidence in this important research area may be useful. Arterial BP in humans physiologically varies from beat to beat, minute to minute, hour to hour, and day to night. This behavior is defined as short‐term variability. Medium‐term variability reflects BP fluctuations on different days (ie, ≥1 week), whereas long‐term BP variability reflects the variation of BP over several months or years.

Different methodological approaches are currently used in clinical practice for evaluating BP variability: through ABPM (short‐term), home monitoring (medium‐term), and office measurements (long‐term visit‐to‐visit variability).

It is worth noting that the first historical study that addressed the clinical significance of BP variability dates back to the early 1990s.5 That seminal paper by Mancia's group, in whom BP was monitored intra‐arterially by the Oxford technique at baseline and after a period of 7 years in a small cohort of patients with essential hypertension, showed a significant, independent correlation between initial and follow‐up target organ damage scores (a composite of electrocardiographic and/or echocardiographic left ventricular hypertrophy, retinopathy, and renal dysfunction) and BP variability (defined as half‐hour standard deviation of 24‐hour mean BP).

In the past 2 decades, increasing evidence has accumulated on the association of short‐ and long‐term BP variability with several validated markers of subclinical organ damage and cardiovascular outcomes.

Early studies, mainly performed in hypertensive cohorts, focused on short‐term variability by using ABPM, a powerful tool for the evaluation of the magnitude of BP circadian fluctuations within a single day, such as those induced by the awake‐asleep rhythm, and the BP response to physical and psychological stressors.6 In patients with essential hypertension, 24‐hour BP standard deviation (ie, an overall measure of short‐term BP variability) has been found to be related to organ damage and its progression over time,7, 8 as well as to cardiovascular morbidity, which has been reported to be higher in patients with a greater BP variability than in those without it independently on the 24‐hour mean BP values.9 As for the general population, the PAMELA (Pressioni Monitorate E Loro Associazioni) study has demonstrated for the first time a positive relationship between BP variability and left ventricular mass index, a biomarker of established prognostic value, that persisted after adjustment for sex, age, and 24‐hour average BP values to account for the greater BP variability of elderly individuals, patients with hypertension, and possibly men.10

More recently, the association between long‐term BP variability (as assessed by visit‐to‐visit variability) and cardiovascular events has been the subject of a growing number of studies.11

One of the most interesting acquisitions in the field of hypertension research in the past decade has been that the protective effects of antihypertensive therapy depend not only on the BP levels achieved during treatment but also on the persistence of BP control between on‐treatment visits. The first observation about the role of visit‐to‐visit variability relates to patients with hypertension with coronary heart disease in whom the positive effect of therapy was directly related to an increasing percentage of visits with office BP <140/90 mm Hg.12 Ten years later, a meta‐analysis including a total of 23 high‐quality cohort studies with 107 434 patients with hypertension confirms and expands the concept that visit‐to‐visit variability is a powerful predictor of cardiovascular complications.13 The authors found that visit‐to‐visit variability of systolic BP predicted all‐cause mortality, cardiac morbidity/mortality, and stroke incidence in patients with low‐risk, moderate‐risk, and high‐risk hypertension.

A previous comprehensive meta‐analysis by Stevens and coworkers14 including 41 studies examined the association of long‐term (clinic monitoring), mid‐term (home monitoring), and short‐term (ambulatory) BP variability with cardiovascular outcomes and mortality. Long‐term variability was significantly associated with all‐cause and cardiovascular disease mortality, cardiovascular disease events, stroke, and myocardial infarction, independent of average BP. Mid‐term and short‐term variability were also associated with mortality, but the predictive value for cardiovascular disease outcomes was less significant than that found for long‐term (visit‐to‐visit) variability. Interestingly, across all analyses, the hazard ratios for coronary heart disease events were smaller than those for stroke, suggesting that the effect observed for cardiovascular disease events may be driven primarily by cerebrovascular events. It is noteworthy, however, that in recent years there has been increased evidence for an association between altered BP variability and risk of coronary events. In a small but carefully designed study, Gondo and colleagues15 found that higher visit‐to‐visit variability in systolic BP after successful percutaneous coronary intervention attributable to ACS was an independent predictor of myocardial infarction during a follow‐up period of 6 to 9 months.

The contribution by Hassan and colleagues4 adds a piece of information on the relationship between short‐term BP variability and cardiovascular complications in the setting of ACS, a clinical condition in which many factors may contribute to acutely alter physiological BP variability. A marked increase in sympathetic tone, myogenic reactivity, activation of renin‐angiotensin system, and abnormal baroreflex sensitivity and release of vasoactive substances have been described to be associated with the onset of ACS. Therefore, ACS may represent a particularly interesting clinical model to investigate the role of short‐term BP variability, which is deeply altered by hemodynamic, humoral, and metabolic changes induced by acute myocardial ischemia.16

In this perspective, a total of 200 consecutive patients (mean age 59 ± 10 years, 72% men) admitted to a coronary care unit for typical anginal pain lasting for >30 minutes with ST‐segment elevation or depression (>1 mm) or new onset of complete left bundle branch block and troponin elevation diagnostic for myocardial necrosis were prospectively evaluated by the authors. Of note, ST‐segment elevation was the most common electrocardiographic pattern, as it was present in approximately two thirds of the population. The main atherogenic risk factors in the total selected sample were in ranking order: hypertension (50%), smoking (47%), type 2 diabetes mellitus (38%), dyslipidemia (25%), and positive family history (20%). Patients with hemodynamic instability, major arrhythmias, renal insufficiency (ie, estimated glomerular filtration rate <60 mL/min), congestive heart failure, morbid obesity, and chronic pulmonary disease were excluded per protocol. BP variability was assessed by a single 24‐hour ABPM performed within the first 2 days of hospitalization in a coronary care unit. The standard deviation of the average of 24‐hour BP was taken as a reference measurement of overall BP variability. As previously mentioned, MACEs consisted of all‐cause death, myocardial reinfarction, cardiogenic shock, stroke, heart failure, hypertensive crisis, and life‐threatening arrhythmias.

During the 7‐day observation period, MACEs occurred in 74 patients, with a 4% overall mortality. The most common event was acute pulmonary edema (14%), followed by arrhythmias (12.5%) and hypertensive crisis (9%). Patients with high systolic BP variability index (defined by values above the median) more frequently had hypertension, were taking more diuretics and angiotensin II receptor antagonists, and less frequently presented with ST‐segment elevation as compared with their counterparts with low BP variability index. In the former group, the incidence of MACEs was approximately 1.7‐fold higher than in the latter (47% vs 27%, P = .003). In multivariate logistic analysis, type 2 diabetes mellitus and systolic BP variability index were the only two independent correlates of MACEs. It should be noted, however, that between the various MACE components, only hypertensive crisis was significantly more frequent in individuals with high BP variability. This was not the case for hard outcomes such as death, reinfarction, stroke, and heart failure. This interesting study clearly indicates that abnormal fluctuations in BP, as assessed by a single ABPM session, are associated with a high incidence of hypertensive crisis, whereas their unfavorable effect on short‐term cardiovascular events in patients with ACS remains hypothetical and needs to be investigated in future studies designed in such a way as to overcome some methodological limitations inherent in this pilot study. In fact, the main limitations of the study by Hassan and colleagues include the lack of outcome data in the medium‐term and long‐term follow‐up, the use of a single BP variability index, the lack of information on the prognostic role of important factors such as the severity of coronary disease as assessed by angiography, and the degree of left ventricular systolic/diastolic dysfunction.

CONFLICT OF INTEREST

The authors report no conflicts of interest.

Cuspidi C, Tadic M, Grassi G. Short‐term blood pressure variability in acute coronary syndrome. J Clin Hypertens. 2017;19:1249–1251. 10.1111/jch.13105