Cardiovascular Disease Markers Linked to Microscopic Strokes

In a 2017 study, researchers examined the link between levels of the cardiovascular disease markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin Y (hs-cTnT), cardiovascular disease, and cortical cerebral microinfarcts – microscopic strokes occurring in the cortex of the brain. The study found that cardiovascular disease markers are linked to microscopic strokes in the cortex, independent of other risk factors for vascular disease.

Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with both the early stages of cardiovascular disease and cognitive impairment and dementia. Cortical cerebral microinfarcts (CMIs) are microscopic strokes that occur within the outer structures of the brain, which are associated with higher processes such as cognition, language, and memory. CMIs have been gaining attention as indicators of vessel-related diseases in the brain due to their implication in cognitive impairment and dementia, and have also been associated with a history of cardiovascular disease. Understanding the potential link between NT-proBNP and hs-cTnT, cardiovascular disease, and CMIs may provide researchers and clinicians with novel strategies for the treatment and prevention of cardiovascular diseases and the vessel-related cognitive impairments.

In a 2017 study published in JAMA Neurology, researchers examined the link between NT-proBNP and hs-cTnT, cardiovascular disease, and cortical CMIs. Participants were recruited from 2 memory clinics in Singapore and were categorized as having no cognitive impairment, cognitive impairment without dementia, vascular cognitive impairment without dementia, Alzheimer’s disease, vascular dementia, or mixed dementia. Information was collected concerning the age, sex, race, educational level, and smoking history of each participant through a questionnaire, and each participant’s medical history – with respect to a history of atrial fibrillation (a type of irregular heart rhythm), ischemic heart disease, congestive heart failure, high blood pressure, high cholesterol, or diabetes – were verified through medical records. Physical examinations measuring height, weight, and blood pressure were also conducted, and levels of NT-proBNP and hs-cTnT in the blood were measured. Cortical and lacunar (occurring within deep brain structures) infarcts and microscopic bleeding were identified and graded using 3-T magnetic resonance imaging (MRI), and the narrowing of blood vessels (which can lead to strokes) were identified and graded using magnetic resonance angiography.

Of the 464 subjects recruited, 243 were included in the final analysis – 221 were excluded due to lower than detectable levels of NT-proBNP or hs-cTnT or the absence of a gradable CMI. Of the 243, 70 (28.8%) had at least 1 CMI – 36 (51.4%) had 1, 20 (28.6%) had 2-4, and 14 (20%) had 5 or more. Non-CMI lacunar and cortical infarcts, microscopic bleeding, and the narrowing of blood vessels were more prevalent in those with CMIs than in those without. Higher levels of NT-proBNP and hs-cTnT were significantly correlated with increasing numbers of cortical CMIs. This association did not remain, however, in those without cardiovascular disease who had 3 or more CMIs. Atrial fibrillation, ischemic heart disease, and congestive heart failure were also associated with cortical CMIs, irrespective of other cardiovascular risk factors.

Overall, the study found elevated levels of the cardiovascular disease markers linked to microscopic strokes in the cortex of the brain, independent of vascular risk factors. Moreover, this association was found to be independent of present cardiovascular disease, suggesting that the pre-clinical conditions which give rise to elevated NT-proBNP and hs-cTnT levels, such as the overstretching or injury of heart muscles, may contribute to the development of CMIs. As this study did not examine NT-proBNP and hs-cTnT levels, the prevalence of cardiovascular conditions, and the number of CMIs developed over time, no causal conclusions can be drawn. The brain imaging technique employed in this study, 3-T MRI, may have been insufficient to detect CMIs less than 2 mm in diameter. Future research may, therefore, benefit from the use of more powerful MRI techniques with higher resolution, such as 7-T MRI. The relationship, if any, between NT-proBNP and hs-cTnT levels, cardiovascular disease, infarct size, and cognitive impairment may also be worth exploring, and therapeutic strategies which lower NT-proBNP and hs-cTnT levels may be of use in the prevention of CMIs.

Written By: Raishard Haynes, MBS