Searching cerebrovascular risk indicators for hypertensive patients: Is Framingham Stroke Risk Profile “the magic bullet”?

Arterial hypertension is one of the main risk factors for cerebrovascular diseases; even a 10% reduction of diastolic pressure offers a 40% reduction of death from cerebrovascular diseases.1 However, morbidity has not been reduced to a similar extent and an increasing number of patients suffer from recurring strokes and develop progressive cognitive impairment and dementia.2

Dementia is characterized by intellectual impairment, which interferes with social and occupational daily functions. Among the different aspects of the clinical picture are memory decline, aphasia, agnosia, loss of muscular strength, and deterioration of executive function. Mental deterioration is associated with a significant worsening of health and quality of life in the elderly. Early identification of cognitive impairment and correction of its modifiable risk factors is therefore a priority in clinical research.3, 4

Longitudinal studies have shown that arterial hypertension in adult life is a predictive factor for both vascular and degenerative dementia in the elderly and the prevention of cognitive decline and dementia is one of the main goals of antihypertensive therapy.5 Arterial hypertension causes cognitive impairment and dementia by affecting both the large and small cerebral vessels as well as the heart. The macrovascular atherosclerotic disease causes atherothrombotic brain infarcts that can be either silent or clinically evident as stroke. The microvascular disease results in chronic ischemic changes affecting, to a large extent, the white matter, also known as white matter lesions (WML). Furthermore, hypertension causes left ventricular hypertrophy, atrial fibrillation, and therefore, cardioembolic stroke. The outcome of single or multiple acute events is a stepwise progression to multi‐infarct dementia, while the outcome of chronic microvascular damage is a continuous progression from mild cognitive impairment to overt vascular dementia.6 Microvascular disease causes basal ganglia dysfunction and cortical deafferentation. These processes cause a subtype of vascular dementia, the subcortical syndrome, particularly related to hypertension and to its associated cardiovascular risk factors, characterized by impairment of executive function and attention.6 The vascular alterations also disrupt cerebral blood flow autoregulation and make the brain more susceptible to hypoperfusion during occasional or chronic hypotension that may be caused by inappropriate or excessive antihypertensive therapy. Drug induced hypotension may affect attention and indirectly performance in executive functions.7 Finally, vascular lesions also have a permissive effect on the clinical expression of neurodegenerative dementia of the Alzheimer type.8

Prevention of vascular dementia requires early identification of high‐risk patients and measurable intermediate targets that herald cognitive impairment, to assess the effectiveness of preventive measures. The Framingham Stroke Risk Profile (FSRP) was developed many years ago to evaluate the risk of stroke and suggest risk‐factor modifications to reduce risk.9 It helps to identify people who have increased risk of stroke resulting from borderline levels of multiple risk factors (eg, mild or borderline hypertension) and to facilitate multifactorial risk factor modification. These risk factors include: age, systolic blood pressure, the use of antihypertensive therapy, diabetes mellitus, cigarette smoking, prior cardiovascular disease (coronary heart disease, cardiac failure, or intermittent claudication), atrial fibrillation, and left ventricular hypertrophy by electrocardiogram. Studies have also shown that FSRP associated with the extent of WML10, with silent cerebral infarcts or microbleeds'11 performance in several cognitive domains12 and global cognitive decline.13 This is not surprising when taking into account the above‐mentioned association between subcortical lesions and dysfunctional cognitive domains.

In the present issue, Uiterwijk and coworkers have related FSRP with MRI markers of cerebral small vessel disease and cognitive performance in hypertensive patients.14 Patients with diabetes and atrial fibrillation at baseline examination were excluded, as were patients with overt baseline dementia, or patients that suffered from stroke during follow‐up. The study shows that FSRP is associated with progressive periventricular WML and new microbleeds. However, the association is lost after correction for age, suggesting that aging, not hypertension, is the most important determinant of periventricular WML. No significant associations were found between FSRP and progression of subcortical WML and new lacunes.

The Framingham Stroke Risk Profile was also associated with lower overall cognitive performance and this association remained significant after correction for age. Higher FSRP was associated with lower cognitive performance in overall cognition, executive function, information processing speed, and memory. However, the association of FSRP with executive function lost significance after correction for age, an unexpected finding since executive function is strongly related with hypertension, while memory is mostly correlated with age.7

What does this study add to the current knowledge of hypertension and cerebrovascular complications? It demonstrates that it is possible to follow up subtle changes of cerebrovascular vessel disease (as we already do in clinical activity with carotid intima‐media thickness, atherosclerotic plaque volume, and severity of carotid stenosis). Furthermore, it suggests that the pathogenesis of microbleeds, cerebral small vessel disease, and lacunes are probably heterogeneous and that not all of these complications will respond to antihypertensive treatment to the same extent, stressing the necessity of a multifactorial risk factor approach.

The main limitations of the paper that need to be addressed in future longitudinal studies are the small study cohort and the high dropout rate, as the authors admit. Exclusion of patients with diabetes and atrial fibrillation, frequently associated with high blood pressure, reduce the power of detecting small, but clinically relevant, effects. In fact, both diabetes and atrial fibrillation amplify the impact of blood pressure load on cerebrovascular risk and dementia.15 However, on clinical grounds, our task is to prevent cerebrovascular complications without too much care of which is the most relevant of the many coexisting patient risk factors. Therefore, we urgently need to implement the multifactorial approach that is pinpointed by FSRP.

CONFLICT OF INTEREST

None.

Semplicini A. Searching cerebrovascular risk indicators for hypertensive patients: Is Framingham Stroke Risk Profile “the magic bullet”? J Clin Hypertens. 2018;20:246–247. 10.1111/jch.13176