Cardiovascular disease (CVD) encompasses a spectrum of pathological conditions affecting the heart, blood vessels, and the circulatory system, and stands as the leading cause of mortality and morbidity worldwide. Recent statistics indicate a concerning increase in CVD prevalence, contributing to nearly 30% of global deaths and affecting both male and female populations globally. This rising burden is driven by factors such as population aging and the presence of multiple risk factors. Various risk factors, including cardiometabolic, behavioral, environmental, social, and genetic factors, significantly contribute to the development of CVD. Traditional risk factors such as smoking, alcohol consumption, hypertension, dyslipidemia, and diabetes substantially heighten the risk of CVD. Consequently, understanding CVD prevalence and impact is crucial in addressing this global health challenge.
The prevention and management of CVD can be categorized into primary and secondary prevention. Primary prevention entails the early identification and modification of “lifestyle risk factors,” while secondary prevention focuses on appropriate risk reduction to slow disease progression. Effective prevention and treatment strategies hinge on the identification of individuals at risk of CVD and the establishment of systems that facilitate proactive management.
Hypertension, cardiac hypertrophy, diabetes, and heart failure (HF) are interconnected conditions with significant implications for cardiovascular (CV) health. Elevated blood pressure (BP), a primary risk factor for various CVDs, including stroke, coronary artery disease, atrial fibrillation, and peripheral vascular disease, is also a modifiable factor in HF development. In cases of hypertension, persistent high arterial pressure triggers the enlargement of the heart muscle, known as cardiac hypertrophy, as the heart compensates for elevated arterial resistance. Hypertension substantially increases the incidence of HF, which is responsible for a significant proportion of annual deaths in the United States and entails substantial health-care expenses. Furthermore, individuals with diabetes face more than double the risk of developing HF compared to those without diabetes, even after accounting for factors such as age, hypertension, hypercholesterolemia, and coronary artery disease. Research indicates that diabetes-related heart disease, or diabetic cardiomyopathy (CMP), significantly contributes to diastolic dysfunction and HF in diabetic patients.
HF, a complex chronic heart condition, results in reduced cardiac pumping or filling capacity, leading to high rates of hospitalization and mortality globally. Initially, the heart responds to increased load or cardiac stress by enlarging in size and mass – a compensatory process referred to as pathological cardiac hypertrophy. This enlargement aims to normalize wall stress and maintain CV function at rest. During this compensatory stage, biochemical, molecular, structural, and metabolic changes occur to preserve cardiac function. However, chronic stress or disease eventually leads to ventricular dilation, decreased contractile function, and progression to HF.
Hence, the critical need for discovering novel treatments to prevent or decelerate HF onset cannot be overstated. HF represents a substantial and escalating global health issue, characterized by a high prevalence and mortality rate. Despite advancements in medical interventions, existing therapies merely mitigate disease progression, and heart transplantation remains the only available cure. Animal models simulating hypertensive heart disease are pivotal in exploring potential regenerative treatments, enabling scientists to investigate fundamental mechanisms of HF and uncover fresh therapeutic targets. In addition, existing treatment options, such as conventional pharmacological agents and left ventricular assist devices (VADs), can only postpone HF progression. Consequently, there is an urgent demand for innovative therapies capable of restoring damaged hearts and enhancing the prognosis for HF patients. Identifying and implementing new therapeutic strategies for HF is of paramount importance due to its alarming rise in prevalence and the substantial burden it places on both individuals and society. This review aims to delve into the research and development of inventive and emerging therapies targeting CV risk factors, specifically focusing on hypertension and diabetes with the objective of averting or delaying the onset of HF. It intends to emphasize the significance of inventive strategies for preventing or postponing HF, ultimately contributing to the enhancement of patient outcomes in light of this escalating global health issue.
HF remains a significant public health challenge, with its prevalence expected to rise substantially by 2030 due to an aging population, with persistently high mortality rates despite advancements in treatment. Several risk factors are thought to precede the development of HF. Among these hypertension, commonly referred to as high BP, stands out as a major risk factor and a primary precursor to the initiation and progression of HF.
Hypertension is characterized by elevated BP levels, typically defined as a systolic BP (SPB) ≥140 mmHg and/or a diastolic BP (DBP) ≥90 mmHg. It places additional strain on the heart, leading to structural and functional alterations in the heart muscle, encompassing the hypertrophy of the left ventricle, which, if left unchecked, can evolve into HF. Diastolic dysfunction and HF with preserved ejection fraction (HFpEF) are the most prevalent cardiac complications associated with hypertension, but it also heightens the risk of myocardial infarction (MI) and plays a pivotal role in the intricate network of CVD, making it a significant contributor to the pathophysiological processes culminating in HF with reduced ejection fraction (HFrEF).
Understanding the link between hypertension and HF is pivotal for preventing or delaying the onset of this debilitating condition. The most widely accepted model of hypertensive HF indicates that left ventricular diastolic dysfunction is the initial detectable manifestation of heart disease. Cardiac remodeling, in response to the primary pressure overload, involves an increase in cardiac mass at the expense of chamber volume, resulting from the parallel addition of sarcomeres, ultimately leading to concentric left ventricular hypertrophy. Conversely, in response to primary volume overload (such as obesity, chronic kidney disease [CKD], or anemia), cardiac remodeling entails increased cardiac mass and chamber volume caused by the serial addition of sarcomeres, resulting in eccentric left ventricular hypertrophy. When sustained pressure overload persists, diastolic dysfunction progresses, the concentrically remodeled left ventricle decompensates, leading to hypertensive HFpEF. On the other hand, sustained volume overload results in left ventricular dilation, leading to decompensation of the eccentrically remodeled left ventricle and the development of HFrEF. Combining left ventricular hypertrophy with elevated levels of biomarkers indicating subclinical myocardial injury, such as high-sensitivity cardiac troponin T and N-terminal pro–B-type natriuretic peptide (NT-proBNP), identifies patients at the highest risk of developing symptomatic HF, particularly HFrEF.
The final stage of hypertensive heart disease, often stemming from prolonged pressure and volume overload, manifests as dilated CMP characterized by both diastolic dysfunction and reduced ejection fraction. The connection between hypertension and HF also involves changes in the reninangiotensin-aldosterone system (RAAS), which is over activated due to left ventricular systolic wall stress and further contributes to cardiac hypertrophy. In addition, the sympathetic nervous system (SNS) plays a significant role in left ventricular hypertrophy, overt vasoconstriction, and electrolyte retention, especially sodium. These effects are induced by the compensatory activation of the SNS, which can result in structural and functional changes in the heart, including left ventricular hypertrophy and modified myocardial contractility. Clinically, hypertensive heart disease can be categorized into four ascending degrees based on the pathophysiological and clinical impact of hypertension on the heart:
Recent research advancements in the realm of hypertension treatments have shown significant progress. These discoveries have not only deepened our understanding of hypertension’s underlying mechanisms but have also paved the way for innovative pharmacological and interventional approaches to combat this prevalent condition.
