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Is Cognitive Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
Carl J Pepine, MD, MACC, FESCUniversity of Florida
Gainesville, FL
64 yo! with angina, DOE, HTNEF 68%, LVEDP 22 mmHg, CFR 1.9, LAD Constricts 26% w 10-4Ach
Is CogniLve Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
3 Angina hospitalizations over previous 7 years, 2 with MINOCA.Over past 6 months noted increasing difficulty with recent memory. Memory clinic- Evaluation/diagnosis: “Mild cognitive impairment (MCI), not likely AD”. Neurologist- No motor or sensory defects, battery of tests, brain MRI- loss of volume with “white matter hyperintensities”. • Exercise program: Isometric and aerobic with balance training (Tai chi) • “MIND diet”: Vegetables, especially leafy greens (spinach, kale, and other greens),
nuts, berries, beans, whole grains, fish, poultry, olive oil, and wine)• Donepezil in combination with memantine.• Revaluate in 4-6 months.
The Dilemma: From the perspecLve of CJPWhat Is Known?A large cohort with symptoms/signs suggesSng myocardial ischemia has no obstrucSve epicardial CAD, but…Disorders of coronary endothelial and VSMCs in arteries and microvessels, and cardiomyocytes are prevalent in this cohort, but… These disorders are linked with adverse outcomes but require specialized tesSng to detect and quanSfy. We lack robust data to support guideline recommendaSons. Yet, we have not been successful convincing the general and cardiology specialist physicians to pay aLenMon to these paMents and embrace tesMng required to inform the diagnosis. What can we learn from a another large organ disorder that has vascular, microvascular, and parenchymal components?
Is Cognitive Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
Talking and discussion points:• Case• “Harmony in the microvasculature”- prompted a “national brain effort” in 2012.• Small vessel disease- Cerebral blood flow• Incidence of dementia post stroke, large vessel component • Calcium antagonists, other large and small molecules • Blood-brain barrier breakdown, Ao-cerebral blood vessel coupling• Taxonomy • For the future
Is Cognitive Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
Is CogniLve Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn? (SPRINT MIND & INFINITY Trials)
Some main features of Mssue fibrosis in SVD in the brain
Thompson Stroke 2009;40:e322-30
Microvascular endothelial dysfunction: the heart and beyond (1) Systemic risk factors associated with development of microvascular endothelial dysfunction (2) Imbalance between potent vasodilators and vasoconstrictors associated with endothelial dysfunction (3) Cardiac and systemic manifestations associated with microvascular endothelial dysfunction
Corba MT, et al.European Heart J. 2018;39:4098-4100
Is Cognitive Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
National Plan to address Alzheimer’s Disease-related Dementias ([email protected]). The Plan (NAPA), originated in 2012, establishes five ambitious goals to both prevent future cases of AD and related dementias (ADRD), and to better meet needs of millions of American families currently facing this disease. The Plan has yearly updates.GOAL 1: PREVENT AND EFFECTIVELY TREAT ADRD BY 2025GOAL 2: ENHANCE CARE QUALITY AND EFFICIENCYGOAL 3: EXPAND SUPPORTS FOR PEOPLE WITH ADRD AND THEIR FAMILIESGOAL 4: ENHANCE PUBLIC AWARENESS AND ENGAGEMENTGOAL 5: IMPROVE DATA TO TRACK PROGRESS
Is Cognitive Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
NaMonal Plan to address Alzheimer’s Disease-related DemenSas ([email protected]). GOAL 1: PREVENT AND EFFECTIVELY TREAT ADRD BY 2025- prompted major iniSaSves by NIH
hlps://grants.nih.gov/grants/guide/noSce-files/NOT-AG-18-001.htmlhlps://grants.nih.gov/grants/guide/pa-files/PAR-18-029.htmlhlps://grants.nih.gov/grants/guide/pa-files/PAR-18-413.htmlhlps://grants.nih.gov/grants/guide/pa-files/PAR-18-497.htmlhlps://grants.nih.gov/grants/guide/pa-files/PAR-18-516.htmlhlps://grants.nih.gov/grants/guide/pa-files/PAR-18-519.htmlhlps://grants.nih.gov/grants/guide/pa-files/PAR-18-544.htmlhlps://grants.nih.gov/grants/guide/pa-files/PAR-18-545.htmlhlps://grants.nih.gov/grants/guide/pa-files/PAR-18-661.htmlhlps://grants.nih.gov/grants/guide/pa-files/PAR-18-760.html
Is CogniLve Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
https://grants.nih.gov/grants/guide/rfa-files/RFA-AG-18-013.htmlhttps://grants.nih.gov/grants/guide/rfa-files/RFA-NS-18-015.htmlhttps://grants.nih.gov/grants/guide/rfa-files/RFA-AG-18-020.htmlhttps://grants.nih.gov/grants/guide/rfa-files/RFA-AG-18-021.htmlhttps://grants.nih.gov/grants/guide/rfa-files/RFA-AG-18-022.htmlhttps://grants.nih.gov/grants/guide/rfa-files/RFA-AG-18-023.htmlhttps://grants.nih.gov/grants/guide/rfa-files/RFA-NS-18-024.htmlhttps://grants.nih.gov/grants/guide/rfa-files/RFA-AG-18-025.htmlhttps://grants.nih.gov/grants/guide/rfa-files/RFA-AG-18-026.htmlhttps://grants.nih.gov/grants/guide/rfa-files/RFA-AG-18-027.html
In 4-years Total 20
Is CogniLve Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
• Reduced cerebral blood flow (CBF), occurs early in development of cognitive impairment (MCI, Alzheimer disease, and other dementias) and contributes to accelerate disease progression.
• Ample evidence exists indicating that “small vessel disease (SVD) in the brain is the most prevalent neurological disorder ever described”.
• Also a large vessel component-Incidence of dementia 50X higher in the year after stroke vs general population; excess risk is also increased, although substantially lower, after a TIA.
• Calcium antagonists reduce BP and increase CBF, particularly in the hippocampus. These findings not only indicate preserved cerebral autoregulation in dementia but also support potential beneficial cerebrovascular effects of antihypertensive treatment.
Nature Medicine | VOL 25 | FEBRUARY 2019 | 270–276 |
Nature Medicine | VOL 25 | FEBRUARY 2019 | 270–276 |
Is CogniLve Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
Pathophysiologic basis of coronary microvascular and vasomotor and disorders is understudied!• Disease processes may differenSally affect funcSon of epicardial conduit arteries and
the microcirculaSon. • In paSents with INOCA, risk factors for macrovascular coronary atherosclerosis are
prevalent. • Atherosclerosis associates with low coronary shear stress, a determinant of major
adverse cardiac events. • Microvascular and other cardiac pathology: remodeling of vascular wall, inflammaSon,
capillary rarefacSon, arteriolar dysfuncSon, cardiac pericytes, alteraSons in composiSon/volume of extravascular (intersSSal) matrix, and myocardium.
Is Cognitive Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
• CMD-key subgroups of paSents (endotypes) within an undifferenSated, heterogeneous populaSon with or without atherosclerosis; these endotypes are:• Microvascular angina (MVA), • VasospasSc (variant) angina (VA), • Both or, • None and,• Others
• DisSnguishable by mechanism(s) of disease and/or response(s) to linked therapy? • But need a beler taxonomy
Is CogniLve Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
• Need better taxonomy. Multiple Etiology Dementias (MEDs) vs “Multiple Etiology Ischemic Syndromes (MEIS)”.
• Funding for much more clinical investigation.• Era of “pragmatic trial design”.• Training: T32s, ACCSAP, etc. • Workshops: NIH, ACC, AHA, ESC, etc.
• Public support. It’s a serious issue the consumes tremendous resouces and not only a women’s issue!
Is Cognitive Impairment the Brain’s Version of Microvascular Angina? If so, what can we learn?
Conclusion:
Perhaps we can learn from what they have done well?