Arterial Hypertension in Patients with Heart Failure

Javier Díez, MD, PhDabc∗,     aDepartment of Cardiovascular Sciences, Centre of Applied Medical Research, Pamplona, Spain; bDepartment of Cardiology and Cardiac Surgery, University Clinic, Pamplona, Spain; cUniversity of Navarra, Pamplona, Spain. Email: jadimar@unav.es

∗Department of Cardiovascular Sciences, Centre of Applied Medical Research, Av. Pío XII 55, Pamplona 31008, Spain.

Hypertensive heart disease (HHD) has been considered the adaptive hypertrophy of the left ventricle wall to increased blood pressure. Recent findings in hypertensive animals and patients now challenge this paradigm by showing that HHD also results from pathologic structural remodeling of the myocardium in response to hemodynamic and nonhemodynamic factors that are altered in arterial hypertension. The possibility that hypertensive patients predisposed to develop heart failure may be detected before the appearance of clinical manifestations provides a new way to prevent this major arterial complication.

Keywords

Arterial hypertension

Ejection fraction

Heart failure

Left ventricular hypertrophy

Myocardial remodeling

Key points

• Hypertension carries the highest population-attributable risk for heart failure together with coronary heart disease, and as a comorbidity is present in most patients with heart failure.

• There is interindividual variability in the progression from hypertension to heart failure in both the geometry of left ventricular growth and the level of ejection fraction.

• The assessment of the hypertensive failing heart must combine imaging and biochemical markers of the structural and function alterations of the myocardium.

• The prevalence of heart failure calls for prevention efforts, and arterial hypertension is a prime target for such interventions.

• Because arterial hypertension may complicate heart failure, adding further morbidity and mortality risk, its management influences the prognosis of patients with heart failure.

Introduction

Arterial hypertension remains a major public health problem associated with considerable morbidity and mortality. In general, arterial hypertension may damage the coronary subepicardial tree, the cardiac muscle, and the aortic valve (Fig. 1). Because increased blood pressure (BP) is one of the major risk factors that facilitates coronary atherosclerosis, the prevalence of arterial hypertension is greater than 60% in patients with ischemic heart disease.1 In contrast, hypertensive heart disease (HHD) can be defined as the response of the myocardium to the afterload imposed by increased BP that leads to left ventricular (LV) hypertrophy (LVH).2 In addition, the prevalence of aortic valve sclerosis is higher in hypertensive patients than in subjects with normal BP, namely in aged people.3 Although ischemic heart disease, HHD, and aortic valve disease may all facilitate LV dysfunction and cause heart failure (HF), and coexist in hypertensive patients, this article focuses on HHD. Therefore, different aspects of the epidemiology, pathophysiology, and clinical handling of HF related to HHD are reviewed. In addition, because arterial hypertension has been reported to be the most common comorbid condition in patients with HF, some aspects related to its impact on the clinical evolution and handling of HF are also considered.

Fig. 1 Pathways leading to heart failure (HF) and other clinical manifestations such as arrhythmias and ischemic syndrome in arterial hypertension. CRFs, cardiovascular risk factors.

HHD as a cause of HF

Epidemiologic Aspects

Epidemiologic data from the Framingham Study provide insights into modifiable risk factors that promote HF.4–6 In this regard, based on population-attributable risks, hypertension has the greatest impact, accounting for 39% of HF incidence in men and 59% in women. Hypertension increased the age-adjusted and risk-factor adjusted hazard of HF 2-fold in men and 3-fold in women, with a greater impact of the systolic than diastolic BP. Because that the pattern of HF risk factors is likely to vary across world regions based on risk factor prevalence and quality of health care, a recent systematic review and pooled analysis in 6 world regions revealed that hypertension prevalence was high in patients with HF in all regions but the highest in eastern and central Europe and sub-Saharan Africa (age and sex adjusted, 35.0% and 32.6%, respectively).7

The burden of HF is also high in hypertensive patients under treatment. A systematic review of 23 hypertension trials performed between 1997 and 2007 including 193,424 patients revealed a 28.9% incidence of new HF cases.8 The development of HF was more prevalent in older, black, diabetic, and very-high-risk individuals.

Examination of the baseline characteristics of patients with HF and reduced ejection fraction (HFREF) and patients with HF and preserved ejection fraction (HFPEF) (N = 19,519) included in the Digitalis Investigation Group trials, the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) trials, and the I-PRESERVE (Irbesartan in Heart Failure with Preserved Systolic Function Trial) trial shows that the hypertensive cause of HF was assigned to more than 20% of patients with HFPEF, but to less than 10% of patients with HFREF.9 Therefore, the notion has emerged that arterial hypertension facilitates the development of HFPEF.

However, this notion is not always supported by epidemiologic data. Ho and colleagues10 recently reported the findings of the study on new-onset HF cases between 1981 and 2008 in Framingham Heart Study participants, classified into HFPEF and HFREF (ejection fraction [EF] >45% vs ≤45%). The investigators used Cox multivariable regression to examine predictors of 8-year risk of incident HF and competing-risks analysis to identify predictors that differed between HFPEF and HFREF. Among 6340 participants (aged 60 ± 12 years), 512 developed incident HF. Of 457 participants with EF evaluation at the time of HF diagnosis, 196 (43%) were classified as HFPEF and 261 (56%) as HFREF. Fourteen predictors of overall HF were identified. Older age, diabetes mellitus, and a history of valvular disease predicted both types of HF. Higher body mass index, smoking, and atrial fibrillation predicted HFPEF only, whereas male sex, higher total cholesterol, higher heart rate, arterial hypertension, LVH, previous symptomatic cardiovascular disease, and left bundle-branch block predicted HFREF only.

In combining individual patient data from 31 studies (41,972 patients), the investigators of the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) showed that patients with HFREF (N = 10,347) have higher total mortality compared with patients with HFPEF (N = 31,625).11 However, this difference was seen regardless of whether arterial hypertension was the cause of HF or only a comorbidity. Thus, arterial hypertension did not seem to influence the prognosis of patients with HF.

Pathophysiologic Aspects

The conventional pathophysiologic view of HHD has been that initially arterial hypertension is associated with concentric LVH because the LV wall thickens in response to increased BP as a compensatory mechanism, and that subsequently, after a series of poorly characterized events, compensated LVH transitions to HF.12 However, experimental and clinical evidence from the last decades indicates that arterial hypertension may progress to HF through several pathways (Fig. 2).13 First, it is well known that patients with concentric LVH develop HFPEF. Second, concentric LVH may also progress to HFREF, most commonly via an interval myocardial infarction, although transition from concentric LVH to HFREF may occur even in the absence of myocardial infarction. Third, some hypertensive patients may develop a geometric pattern of LV growth that is different from concentric hypertrophy (eg, concentric remodeling and eccentric LVH) and that may also evolve to either HFPEF or HFREF. These different possibilities of progression from arterial hypertension to HF may be the result of the influences of modulator factors (eg, genetic background, gender, aging, lifestyle factors, obesity, and diabetes mellitus) as well as of the structural changes of the myocardium that occur in response to hemodynamic and nonhemodynamic mechanisms.

Fig. 2 Pathways leading to HF in HHD. The thickness of the continuous lines represents the importance of the pathway in terms of frequency. The dotted line represents the possibility that HFPEF may evolve to HFREF. cLVH, concentric LVH; cR, concentric remodeling; eLVH, eccentric LVH; MI, myocardial infarction.

Cardiomyocyte hypertrophy leading to LV wall...