The Hypertensive Heart: New Observations and Evolving Therapeutic Imperatives

Twenty‐three centuries ago, Herophilus ¹ first interpreted the cardiac cycle as being divided into two phases: diastole, which he termed the active distension or pushing apart of the heart's walls or arteries, and systole, which he viewed as the passive return of the heart's walls to their original position. The ancient Greeks appreciated the importance of diastole, and their realization that diastole reflects an active phase of the cardiac cycle has significant parallels with modern understanding. Contemporary investigations have revealed that the isovolumic phase of diastolic relaxation is sensitive to ischemia, which impairs the energy‐dependent uptake of sarcoplasmic calcium. In the field of high blood pressure, we now recognize abnormal diastolic performance as the earliest perceptible functional abnormality in the hypertensive heart.

Congestive heart failure is increasing in prevalence, with hypertension as a major underlying factor, ² and a large proportion of heart failure patients have normal left ventricular ejection fractions. ³ , ⁴ These patients demonstrate abnormal diastolic behavior, and do not necessarily have a benign prognosis. ⁵ Of particular significance is the recent finding that hypertensive pulmonary edema is based on an exacerbation of diastolic dysfunction by hypertension. ⁶

In this issue of The Journal of Clinical Hypertension, authors DeSimone and Palmieri explore the relations between diastolic properties of the heart, left ventricular hypertrophy (LVH), blood pressure regulation, incipient abnormalities of systolic function, and subsequent heart failure. ⁷ In this technically comprehensive contribution, the investigators point out that subtle impairments in systolic function (diminished left ventricular midwall shortening on echocardiography) may be noted once abnormal prolongation of the active, energy‐consuming, early phase of diastole is observed. These changes appear well before overall systolic performance deteriorates, as manifested by a fall in the ejection fraction. In an earlier investigation, ⁸ decreased midwall shortening in asymptomatic subjects was shown to be linked with unfavorable findings, such as increased peripheral resistance, elevated heart rate, low levels of high‐density lipoprotein cholesterol, and increased carotid artery wall thickness. Diastolic abnormalities are strongly associated with the appearance of LVH, which itself represents a compensation for increased hypertensive afterload stress. Diastolic dysfunction can be observed in 25% of asymptomatic hypertensive patients, but is witnessed in greater than 80% of patients who have LVH. ⁹ , ¹⁰

What are the treatment implications of these findings? The authors propose that recognition of the role of incipient diastolic functional impairments may lead to a more effective strategy in hypertension treatment. Such therapy is likely to prove most useful when applied early, and, one may propose, at lower blood pressure treatment thresholds, consistent with current guidelines and multiple recent therapeutic trials assessing both systolic and diastolic hypertension. However, it is not yet clear that specific measurements of diastolic function should receive direct consideration in targeting pharmacotherapy. Even without such measurements, early treatment of high blood pressure with strict adherence to current goals can be expected to produce benefit, whether by preventing, stabilizing, or improving abnormal diastolic performance of the heart. Several classes of antihypertensive agents may exert similar effects on diastolic behavior—for instance, calcium channel blockers and angiotensin‐converting enzyme (ACE) inhibitors. ¹¹ , ¹² In regard to the closely related finding of LVH, data suggest that normalizing pressure overload can improve prognosis if LVH regression is achieved. ¹³ Most pharmacologic classes are capable of LVH regression, including thiazide diuretics, β‐adrenergic blockers, calcium channel blockers, ACE inhibitors, and angiotensin receptor blockers. ¹⁴ Of these agents, diuretics, ACE inhibitors, and angiotensin receptor blockers may be the most effective. Further studies are now evaluating a spectrum of therapies to explore whether reducing LVH truly provides a better prognosis, even apart from the level of blood pressure control. ¹⁵ , ¹⁶ The results will be received with great interest, and may well support current recommendations favoring vigorous treatment in early stages of hypertension.