Rethinking of the hypertension management in the elderly with comorbidity: Should we forget the age in treating elderly hypertensives?

Driven by declining fertility rates and increasing life expectancy population aging is becoming a global phenomenon with creeping higher age‐specific relevance of blood pressure (BP). The number of individuals aged 65 or older is estimated to achieve nearly 1.5 billion in 2050 while the prevalence is expected to rise to 29% by 2025. ¹ Observational studies have indicated that the CV risk increased linearly with systolic blood pressure (SBP) levels above 115 mm Hg and diastolic blood pressure (DBP) above 75 mm Hg throughout middle and old age. ² Although antihypertensive therapy has been suggested to bring benefits among a range of subpopulations, treating hypertension adequately in advanced age faced barriers owing to the preoccupation that the elderly may have a poor tolerability to BP‐lowering medications. Older patients are prone to have impaired vital organ perfusion with presentations of posture hypotension, falls, and renal impairment, which may be worsened by BP‐lowering medications. Nevertheless, evidence from randomized controlled trial (RCT) has shown that antihypertensive interventions were generally tolerated and reduced cardiovascular events and mortality in older patients. ³ , ⁴ , ⁵ The 2017 ACC/AHA hypertension clinical practice guideline recommends a SBP target of <130 mm Hg in geriatric populations, similar to that in the others. ⁶ Though the ESC guideline recommended treating SBP values <130 mm Hg should be avoided for elderly hypertensives aged 80 years or older ⁷ given the fact that present RCTs have not included patients in the context of comorbidities and reduced life expectancy. In this issue of Journal of Clinical Hypertension, Noriko Kikuchi et al conducted a post hoc analysis of the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Heart Disease (HIJ‐CREATE) trial to investigate the outcomes of a lower final achieved SBP vs. the conventional BP level in elderly patients with hypertension and documented CAD, which concluded that a lower SBP target may be appropriate even in elderly patients with hypertension and CAD. ⁸

The relationship between hypertension and CAD was complicated but has been well studied. However, the optimal BP target in hypertensive patients with CAD remains inconsistent, and a J‐curve relationship between achieved BP and subsequent cardiovascular events has been identified in observational studies. ⁹ , ¹⁰

Since coronary perfusion occurs in diastole a lower DBP might compromise coronary flow reserve in patients with a fixed coronary stenosis and lead to decline of myocardial perfusion and subsequent adverse consequences. It should be emphasized that, for a vital organ with high flow and low impedance, coronary perfusion might also be governed by the principle similar to the cerebral autoregulation rather than a linear pressure‐flow relationship. ¹¹ As such, the coronary flow might not be compromised by a lower DBP given the reset of the lower autoregulatory boundary in certain pathological conditions. Besides, such a mechanism could not help explain that J‐curve relationship was seen in lower SBP as well; therefore, additional hypotheses have been proposed to explain the phenomenon. ¹² , ¹³ Recently, another more plausible explanation for the J‐curve phenomenon, the reverse causation, has been proposed. ¹⁴ When we observe a worse outcome in the group with lower achieved BP, we usually intuitively conclude that the lower BP leads to the worse outcome. However, such an association may be resulting from a relationship in the opposite direction that the outcome (mortality and cardiovascular events) can cause BP reduction. The concept has been clearly demonstrated in a recently published cohort study. ¹⁴

In the management of hypertension in the elderly population, caution is usually exercised by considering the chronological age rather than the biologic age. The therapeutic strategy of one size fits all cannot be applied because of the enormous functional heterogeneity in geriatric individuals. ¹⁵ Besides, whether age is an effect modifier on the benefit or harm of antihypertensive treatment for elderly hypertensives has not been systematically investigated until a recently published systematic review. ³ Huang et al by conducting a systematic review with meta‐regression analysis on 18 randomized controlled trials demonstrated that the relative risks of a more aggressive BP lowering strategy were similar between patients aged older or less than 75 years for all outcomes except for renal failure. This systematic review concluded that age had trivial effect modification on most outcomes except for renal failure in treating elderly hypertensives. However, close monitoring of renal function is warranted in the management of elderly hypertension. As suggested by the current body of evidence, what we should question may be “should we forget the age in treating elderly hypertensives?”

To clarify the potential modifying effects of age on BP lowering for various adverse outcomes, Noriko Kikuchi et al reported step‐up hazard ratios of major adverse cardiac events along with mean achieved systolic blood pressure by each age‐groups in hypertensive patients with angiographically documented CAD. ⁸ The result implied that a lower SBP target may be more appropriate even in elderly patient with hypertension and CAD.

Yet the clinical relevance of BP target in geriatric population with CAD remains to be elucidated. First, the study conducted a post hoc analysis of an RCT that compared the effects of different antihypertensive agents rather than different SBP targets. The comparisons were made for different final achieved SBP levels instead of SBP targets. In contrast, Systolic Blood Pressure Intervention Trial (SPRINT), ¹⁶ Secondary Prevention of Small Subcortical Strokes (SPS3) trial, ¹⁷ and Usual versus tight control of systolic blood pressure in non‐diabetic patients with hypertension (Cardio‐Sis) ¹⁸ are RCTs comparing the outcomes between different BP targets directly. Second, reverse causation ¹⁴ and residual confounding are two important intrinsic limitations for the analysis of observational study comparing different achieved BP. The former even more seriously endanger the validity of the study conclusion. To what extent BP‐lowering treatment benefits the elderly hypertensive patients with CAD remains to be determined by RCTs in the future.

The present study recruited more than 80% of participants underwent coronary revascularization and suggested a lower BP was associated with better clinical outcomes in patients with hypertension and CAD. The potential benefits of BP‐lowering treatment have now been observed in the elderly population with comorbidity. Though clinicians should be aware of treating the elderly by careful monitoring for any adverse effects or tolerability associated with BP‐lowering intervention. Further RCTs are required to overcome the important intrinsic caveats of observational studies.

CONFLICT OF INTEREST

None.