Abbreviation list

CKD: chronic kidney disease

CVD: cardiovascular disease

MMSE: mini-mental state examination

MoCA : Montreal Cognitive Assessment

Take-home messages

1. Age-related structural and functional changes of the cardiovascular system and the kidneys determine accelerated cardiometabolic decline.
2. Cognitive decline is common in older patients with CKD, this is due to the presence of cardiovascular risk factors but also to the toxic effect derived from a decrease of kidney function 
3. A comprehensive approach is necessary in older patients with cardiovascular and kidney disease.

Introduction

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are two leading health concerns in the ageing population, often interrelated and acting synergistically to worsen health outcomes. As people age, the prevalence of both conditions increases, posing significant challenges to healthcare systems worldwide. The intersection between kidney disease and cardiovascular disease is particularly relevant in older adults due to individual physiological age-related changes, as well as the fact that these diseases tend to progress in parallel. The older population is particularly vulnerable to the compound effects of kidney and cardiovascular dysfunction, making early identification, prevention, and management of these diseases crucial [1].

Prevalence of kidney disease and cardiovascular disease in older adults

It is estimated that approximately 10–15% of adults worldwide suffer from CKD, with a higher incidence in older individuals. Studies suggest that more than 30% of adults aged 65 and older exhibit some form of kidney dysfunction, ranging from mild to severe stages. The same population also faces a higher risk of developing cardiovascular diseases such as hypertension, coronary artery disease, heart failure, and stroke.

The relationship between kidney disease and cardiovascular disease in older patients can be complex and multifaceted. The presence of chronic kidney disease accelerates the development and progression of cardiovascular diseases, whereas cardiovascular disease can lead to kidney injury, forming a vicious cycle of worsening health outcomes [2]. Understanding this bidirectional relationship is essential for providing comprehensive care to older individuals with comorbid kidney and heart conditions.

Pathophysiology of kidney disease and cardiovascular disease in older patients

Mechanisms linking kidney disease and cardiovascular disease

The relationship between kidney disease and cardiovascular disease is often described as the "cardiorenal syndrome," a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. This phenomenon can occur through several mechanisms, such as hypertension, the most common risk factor for both CKD and CVD. High blood pressure can damage the small blood vessels in both the kidneys and the heart, leading to decreased organ function. Hypertension can cause glomerulosclerosis, tubulointerstitial fibrosis, left ventricular hypertrophy, coronary atherosclerosis, and can cause both heart and kidney failure[3].

Atherosclerosis and vascular calcifications are common in both CKD and CVD. As kidney function deteriorates, levels of uremic toxins increase, contributing to inflammation and endothelial dysfunction, which predispose individuals to cardiovascular events such as heart attacks and strokes [2]. In CKD, disturbances in calcium-phosphate metabolism, increased parathyroid hormone levels, and reduced kidney clearance of phosphate can contribute to vascular calcification. This process is linked to a higher risk of arterial stiffness, which further exacerbates cardiovascular disease [4, 5]. Both CKD and CVD are characterised by chronic low-grade inflammation and oxidative stress, which contribute to endothelial dysfunction, increased arterial stiffness, and myocardial damage. Elevated levels of pro-inflammatory cytokines, such as interleukin-6 and tumour necrosis factor-alpha, are commonly seen in patients with CKD and have been shown to contribute to the pathogenesis of cardiovascular events.

Effect of ageing on the cardiovascular and renal systems

The ageing process itself contributes to the increased burden of both kidney and cardiovascular diseases. As people age, the kidneys undergo structural and functional changes, including a decline in the glomerular filtration rate, which leads to a reduced ability to excrete waste products and regulate fluids and electrolyte balance. Simultaneously, the cardiovascular system undergoes changes such as thickening of the left ventricle, reduced diastolic function, and increased arterial stiffness [4, 5]. These changes make older adults more susceptible to the deleterious effects of CKD and CVD.

Clinical implications and risks for older patients

Older adults with both kidney disease and cardiovascular disease face significant challenges in managing their health [6]. The coexistence of these conditions often results in poorer outcomes compared to those with only one of the diseases. These patients experience an increased risk of morbidity and mortality. Several studies have shown that CKD significantly increases the risk of mortality in older adults, particularly from cardiovascular causes. Older individuals with end-stage renal disease have a significantly higher risk of death from heart-related complications than those without kidney disease.

Moreover, older patients with both CKD and CVD are often prescribed multiple medications to manage their conditions, which increases the risk of adverse drug interactions and side effects. Additionally, kidney dysfunction can affect the pharmacokinetics of many cardiovascular drugs, such as antihypertensives, anticoagulants, and diuretics, leading to an increased risk of drug toxicity or inadequate therapeutic effects  [1].

Cognitive decline in patients with CKD and CVD

Cognitive decline is a common condition in older individuals with CKD and CVD. The interplay between kidney function, heart health, and cognitive performance is not only intricate but also mutually reinforcing, with each condition exacerbating the other [3, 7, 8]. Understanding these interconnections is crucial for improving outcomes and providing more effective treatment strategies for ageing populations.

As these conditions often coexist, they form a complex and interrelated triad that significantly contributes to reduced quality of life, increased healthcare utilisation, and greater mortality risk.

Cardiovascular disease, particularly conditions like hypertension, atherosclerosis, and heart failure, has long been associated with cognitive decline. The impact of heart disease on cognitive function is evident in conditions such as vascular dementia which is very often caused by cerebral small vessel disease. These lesions, which are associated with executive dysfunction, memory impairment, and other cognitive deficits, are particularly found in older adults with hypertension and heart disease [9].

Other mechanisms can also cause cognitive decline. The reduced ability of the kidneys to filter waste products leads to the accumulation of uremic toxins in the blood. These toxins, such as urea and creatinine, can cross the blood-brain barrier and contribute to cognitive dysfunction by promoting inflammation, oxidative stress, and neuronal damage in the brain [3, 10, 11].

The interplay between kidney disease, cardiovascular disease, and cognitive decline is multidirectional. Each condition not only increases the risk of developing the others but also exacerbates their progression. This creates a cyclical pattern of worsening health, with significant impacts on both physical and mental well-being in older adults.

For example, individuals with CKD are more likely to develop hypertension, which not only accelerates cardiovascular disease but also reduces cerebral blood flow, increasing the risk of cognitive impairment. Conversely, cognitive decline can make managing cardiovascular disease and kidney function more difficult, as patients with impaired cognitive function may have trouble adhering to treatment regimens, attending medical appointments, or managing their symptoms effectively. This triad also creates challenges in clinical practice. For healthcare providers, it becomes essential to consider the interconnected nature of these diseases when diagnosing and treating older patients. A holistic approach to treatment, which addresses all three conditions simultaneously, is crucial for improving patient outcomes.

Clinical implications and management strategies

Early detection and intervention are key to preventing or slowing the progression of kidney disease, cardiovascular disease, and cognitive decline.

Regular screening for CKD and CVD in older adults is essential to identify individuals at risk for cognitive decline. Cognitive screening should also be part of routine evaluations for older patients. Standardised cognitive tests such as the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA) can help identify early signs of cognitive impairment and allow for timely intervention [9, 12].

Given the interconnected nature of these diseases, a comprehensive and multidisciplinary treatment approach is necessary. The key elements are the management of cardiovascular risk factors, such as controlling blood pressure, reducing cholesterol, and preventing atherosclerosis as these are all crucial for both heart and kidney health. For patients with CKD, slowing the progression of kidney disease is essential. This can be achieved through lifestyle modifications, such as dietary changes (e.g., reducing salt and protein intake), controlling blood pressure, and, in some cases, using medications like angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

While there is no cure for cognitive decline, certain strategies may help slow the progression. These include cognitive training, social engagement, and physical activity. Additionally, managing cardiovascular risk factors and controlling CKD can help preserve brain health by improving cerebral blood flow [12].

Conclusion

The interrelationship between kidney disease, cardiovascular disease, and cognitive decline represents a significant challenge to the ageing population. These conditions are not only highly prevalent in older adults but also mutually reinforcing, leading to a cascade of health complications and eventually, multiple organ failure. As these diseases share common risk factors and underlying mechanisms, a comprehensive, multidisciplinary approach to diagnosis and treatment is essential. By focusing on prevention, early detection, and integrated management strategies, we can improve outcomes and quality of life for older adults facing the burden of kidney disease, cardiovascular disease, and cognitive decline. A comprehensive approach that includes early diagnosis, lifestyle modifications, and appropriate pharmacologic management is crucial in managing older patients with both CKD and CVD. Additionally, addressing the unique challenges posed by polypharmacy, frailty, and comorbidities in the elderly population is essential to improving health outcomes. By prioritising prevention and intervention strategies, healthcare providers can help mitigate the impact of these diseases and enhance the quality of life for older adults.