Comparison of Effectiveness of Combination of Valsartan and Hydrochlorothiazide Versus Valsartan Alone in the Treatment of Hypertensive Heart Disease

Background and Rationale:

Hypertension (HTN) is a chronic medical condition characterized by persistently elevated blood pressure, which poses significant health risks worldwide. The global burden of hypertension has been steadily increasing, with current estimates indicating a prevalence of approximately 30% in the general population and up to two-thirds in individuals over 60 years of age. Epidemiological studies have demonstrated that between 1990 and 2019, the number of adults aged 30-79 years with hypertension doubled globally, reaching more than one billion affected individuals in 2019. The prevalence is projected to rise to 1.56 billion by 2025, particularly in rapidly developing countries with limited access to early detection, screening, and healthcare resources.1,2

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Prolonged uncontrolled hypertension can result in hypertensive heart disease (HHD), a condition characterized by structural and functional cardiac alterations due to chronic pressure overload. HHD encompasses a spectrum of cardiac changes, including left ventricular hypertrophy (LVH), diastolic dysfunction, and, in advanced stages, heart failure with preserved or reduced ejection fraction.3 The pathological mechanisms of HHD are multifactorial, involving neurohormonal activation, vascular remodeling, myocardial fibrosis, and cellular-level changes in cardiomyocytes. These structural and functional abnormalities predispose patients to serious cardiovascular events, including stroke, myocardial infarction, heart failure, and renal failure.4,5

Diagnosis of HHD relies on a combination of clinical, electrocardiographic, and imaging criteria. Electrocardiography (ECG) findings indicative of HHD include LVH as defined by Cornell Voltage Criteria (R in aVL + S in V3 ≥ 28 mm for males and ≥ 20 mm for females) and significant ST-segment changes. Echocardiography is the standard tool for assessing cardiac morphology and function, while cardiac magnetic resonance imaging (cMRI) offers enhanced tissue characterization and helps differentiate HHD from hypertrophic cardiomyopathy (HCM).6

Effective management of HHD requires both control of blood pressure and mitigation of myocardial remodeling. Pharmacological treatment is central to management, with angiotensin receptor blockers (ARBs) such as valsartan commonly prescribed due to their efficacy in reducing blood pressure and preventing left ventricular hypertrophy. Valsartan functions by inhibiting the angiotensin II receptor, reducing vasoconstriction, aldosterone secretion, and myocardial remodeling.7 Despite its proven efficacy, monotherapy may not always achieve optimal blood pressure control, necessitating consideration of combination therapy with other antihypertensive agents.