Cardiovascular Risk Management for All Older Patients?

General benefit of CVRM

The goal of the treatment of cardiovascular risk factors is to prevent major cardiovascular events such as myocardial infarctions, an event more frequent in young adults, and strokes, an event which is more frequent in older adults, potentially leading to disability and loss of quality of life. Vascular dementia can be viewed as a later life manifestation of a cardiovascular event, as a result of major strokes or, probably more commonly, as a result of cerebral small vessel disease due to long time exposure to cardiovascular risk factors [2]. Therefore, these aspects are of paramount importance in dementia care in order to prevent new events and potentially also delay further cognitive and functional deterioration.

In current guidelines, characteristics such as age, sex, and individual frailty are taken into account when determining to what extent blood pressure (BP) and lipids should be lowered [3–6]. Nijskens et al. provided an overview of recommendations on BP-lowering and lipid-lowering according to various guidelines. Nevertheless, no RCT has investigated the role of blood pressure and lipid levels optimalization in adults with dementia.

This raises the question, what are characteristics that make patients with dementia so specific when considering CVRM?

Time to benefit

Some aspects have been stressed in the review of Nijskens et al. Patients with (severe) dementia have a shorter life expectancy compared to older adults without cognitive disorders or dementia [7]. Therefore, the time to benefit for treatment to reduce the risk of (new) cardiovascular events may exceed the patient’s life expectancy. It should be noted that there is a wide range in the spectrum of cognitive dysfunction from mild cognitive impairment to early dementia and also end-stage dementia.

CVRM to delay cognitive decline

CVRM could be a part of multidomain intervention to reduce further cognitive and functional decline even after the diagnosis of dementia, preferably in early stage with potentially the highest time to benefit. CVRM in order to delay further cognitive decline and time to functional dependency could be equally important when discussing functional status and quality of life [8, 9]. The presence of cardiovascular risk factors is associated with the onset of both Alzheimer’s disease and vascular dementia, but also with the progression of cognitive decline in the general population and in adults with mild cognitive impairment [10–12]. It is, however, not clear whether the treatment and control of cardiovascular risk factors reduces the incidence of dementia. Several studies have shown somewhat weak evidence in this direction [13, 14]; however, we have to keep in mind that these trials are not designed to investigate the role of CVRM in preventing cognitive decline. Conversely, other studies on antihypertensive medications have reported no overall effect on slowing the rate of cognitive decline nor a reduction of the rate of brain atrophy in individuals with Alzheimer’s disease [15, 16]. Moreover, in patients with type 2 diabetes, treatment with GLP-1 RAs has shown a slight reduction in the incidence of dementia [17]. Eventually, multidomain intervention on modifiable vascular and lifestyle-related risk factors could improve or maintain cognitive functions in individuals at risk [8].

Considerations for (risk) monitoring

The risk of adverse drug events is a hot topic when dealing with older multimorbid patients with dementia in whom polypharmacy is a very frequent condition [18]. Older adults with cognitive disorders are at high risk of adverse drug events. Moreover, in dementia, the risk of adverse events could be increased by drug-drug interactions but also by therapeutic compliance which can be in some cases suboptimal [19]. Eventually, the incidence of adverse drug reactions in patients with dementia is poorly documented, probably due to underreporting of unspecific or unrecognized signs and the presence of intrinsic memory bias, therefore a close medication monitoring is mandatory. In order to adapt initiated therapy when needed, BP measurement is recommended in ambulant setting with repeated measurements preferably. Not only regular evaluation of BP and lipids, but also monitoring of kidney function is recommended, since a decrease in kidney function could potentially result in adverse drug events.

Thus, during those regular evaluations, clinicians should check BP levels and kidney function, be aware or side-effects, and also evaluate time to benefit in order to make a shared decision on continuation or deprescribing.

Routine evaluation of CVRM in patients with dementia might be even more important than in other adults. Since dementia is mainly, but not only, a disease present in late life, clinicians should take into account the natural course of the hemodynamic profile with aging. Due to vascular aging, decreased diastolic blood pressure (DBP) is more often found at high age and associated with a poorer cardiac condition and elevated arterial stiffening [20, 21]. Although the evidence linking arterial stiffness to cognitive decline and dementia is consistent [22], DBP strongly determines mean arterial pressure maintaining organs perfusion and function [23]. Therefore, low DBP and changes in pulse pressure can negatively influence organs perfusion, potentially affecting the brain and the kidneys, and with that, increasing the risk of side effects. Nevertheless, whether BP lowering will induce orthostatic hypotension and hypoperfusion of the brain, as suggested by Nijskens et al, remains debatable as a recent meta-analysis also including patients with cognitive impairment reported no negative effect of antihypertensive treatment on cerebral blood flow [24].

Conclusion

In conclusion, there is a need for achieving knowledge on the effect and the safety of CVRM in patients with dementia. Individual-based fine tuning is mandatory, making medicine a science of uncertainty and an art of probability [25].