medigraphic.com
ISSN 2954-3835 (Electronic)
ISSN 2683-2828 (Print)

2024, Number S1

<< Back Next >>

Cardiovasc Metab Sci 2024; 35 (S1)

INOCA and microvascular angina in hypertensive women

Madrid-Miller, Alejandra1; García-Jiménez, Yoloxochitl2; Moreno-Ruiz, Luis Antonio3

Language: English
References: 15
Page: s35-39
PDF size: 177.84 Kb.






INTRODUCTION

Ischemic heart disease remains women's most common cardiovascular disease, accounting for one-third of all deaths. Myocardial ischemia can be caused by obstructive or non-obstructive atherosclerotic coronary disease, the latter known by its acronym INOCA (Ischemia with Non-Obstructive Coronary Artery disease), which includes non-significant epicardial coronary disease (< 50% stenosis), macro or microvascular coronary dysfunction (CMD), coronary artery spasm (CAS) and spontaneous coronary dissection.1 Until now, it has been underdiagnosed due to the underutilization of functional studies evaluating microcirculatory or vasomotor disorders. It is estimated that 70% of patients with angina undergoing coronary angiography have INOCA. In the United States, they are around 3 to 4 million persons with this condition, and more than 60% correspond to women.1,2 Women with INOCA are about four times more likely than men to have readmissions and cardiovascular mortality up to 32%.3,4



PATHOPHYSIOLOGY

The pathophysiology of INOCA is multifactorial, not yet fully clarified, and shares the same traditional risk factors associated with coronary atherosclerosis. Systemic arterial hypertension (SAH) is the most prevalent factor in 45 to 59% of cases.4,5 The development of secondary left ventricular hypertrophy (LVH) is associated with symptomatic myocardial ischemia even without coronary lesions.6 Bairey Merz et al3 reported that SAH can also influence myocardial perfusion through vasomotor alterations, endothelial dysfunction (ED), atherosclerosis, and poor vascular autoregulation capacity due to remodeling or hardening of the coronary microvasculature, which together with the deregulation of the aortic-ventricular coupling and subendocardial hypoperfusion contribute to CMD.6 Different studies have shown that ED includes attenuation of endothelium-dependent vasodilation due to reduced bioavailability of nitric oxide (NO) and increased vasoconstrictor response of endothelin-1 (ET-1), prostaglandin H2 and thromboxane A2, in porcine models.7 Additionally, the increase in aortic stiffness is associated with an increase in systolic blood pressure (SBP) and a decrease in diastolic blood pressure (DBP), which leads to an increase in left ventricular afterload and oxygen demand, with subsequent derived ischemia of the reduction of the diastolic perfusion pressure of the myocardium.8



CLINICAL PICTURE

The most frequent symptom is angina, which unlike the typical presentation in obstructive coronary disease, in INOCA, is less intense and with different patterns and location variations. It is more frequently associated with dyspnea, nausea, weakness, fatigue, jaw pain, and intense tiredness, sometimes disabling. Angina can occur during stressful situations or at rest. The aggregation of several comorbidities is less frequent.9 Uncontrolled BP accelerates structural and functional changes in blood vessels, which can potentially trigger myocardial ischemia events.



DIAGNOSIS

It is necessary to assess coronary vascular function to define pathophysiology with invasive or non-invasive diagnostic tests (Table 1), according to the clinical context, risk factors, availability of resources, operator experience, and with the following criteria (Figure 1):1,10

  • 1. Clinical picture and objective evidence of ischemia.
  • 2. Coronaries without significant obstructive lesions and fractional flow reserve (FFR) > 0.80.
  • 3. Coronary flow changes: coronary flow reserve (CFR) < 2.0 in response to a vasodilator (adenosine), evidence of coronary spasm with acetylcholine (ACh) or TIMI (thrombolysis in myocardial infarction) flow change frame count (> 3 beats for vessel filling at rest).



NON-INVASIVE METHODS

The transthoracic echocardiogram (TTE) evaluates the degree of LVH. The velocity of the coronary flow can also be measured through pulsed wave Doppler in the coronary artery at rest and after the administration of dipyridamole. Using this method, the iPOWER study demonstrated that 26% of women with INOCA had changes in FRC velocity < 2.0.11 Functional studies with coronary tomography angiography (CT angiography) and cardiac magnetic resonance imaging (CMR) of stress with dobutamine or adenosine allow detection of alterations in subendocardial perfusion in patients with INOCA, calculating the myocardial perfusion reserve index and the index of microcirculatory resistance (IRM) (≥ 25 U is indicative of CMD).1,10 Positron emission tomography (PET) helps evaluate CFR, calculating the ratio of coronary myocardial flow during adenosine induction of maximal hyperemia and at rest.



INVASIVE METHODS

Angiography is the gold standard. If significant coronary lesions are not observed, it is indicated to assess coronary flow and the arteries' diameter with endothelium-dependent tests such as acetylcholine (Ach) and with endothelium-independent tests such as adenosine and nitroglycerin, the CFR, the IMR, and the FFR.

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) allow the evaluation of vascular remodeling and morphology with functional studies. OCT has been shown to have prognostic value when linked to the assessment of adventitial vasa vasorum and intraplaque neo-vessels to indices of microvascular spasm, epicardial spasm, and IMR in patients with INOCA.12



TREATMENT

Maintaining strict BP control, secondary prevention with lifestyle modifications, cardiac rehabilitation, and drug treatment is essential. However, most of the pharmacological recommendations are based on observational studies with inconsistent results, and to date, the underuse of drugs in adherence to the guidelines has been observed. Pauly et al. reported that administering quinapril compared with a placebo for 16 weeks improved CFR and symptoms.13 In another study in patients with SAH, administration of perindopril for one year produced regression of periarteriolar fibrosis and increased CFR.14 In patients with abnormal vasodilator reserve or CD, calcium antagonists improve exercise tolerance and symptoms. An observational analysis showed that statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and beta-blockers significantly reduced major cardiovascular events and heart failure.15 Dual antiplatelet therapy without thrombi, coronary embolism, and ulcerated or eroded plaques is controversial and has not shown risk reduction.10



CONCLUSIONS

SAH is a highly prevalent CVRF in patients with INOCA and contributes to CMD, so its control is essential to reduce ischemia events. Diagnosis should include vascular function tests, and specific treatment should be established based on the phenotyping of the patient with INOCA.


REFERENCES

  1. Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AH et al. An EAPCI expert consensus document on ischemia with non-obstructive coronary arteries in collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Euro heart J. 2020; 41 (37): 3504-3520. doi: 10.4244/EIJY20M07_01.

  2. Hansen B, Holtzman JN, Juszczynski C, Khan N, Kaur G, Varma B et al. Ischemia with no obstructive arteries (INOCA): a review of the prevalence, diagnosis and management. Curr Probl Cardiol. 2022; 48 (1): 101420. doi: 10.1016/j.cpcardiol.2022.101420.

  3. Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL, Camici PG, Chilian WM et al. Ischemia and no obstructive coronary artery disease (INOCA) developing evidence-based therapies and research agenda for the next decade. Circulation. 2017; 135 (11): 1075-1092. doi: 10.1161/CIRCULATIONAHA.116.024534.

  4. Kenkre TS, Malhotra P, Johnson BD, Handberg EM, Thompson DV, Marroquin OC et al. Ten-year mortality in the WISE study (Women's Ischemia Syndrome Evaluation). Circ Cardiovasc Qual Outcomes. 2017; 10 (12): e003863. doi: 10.1161/CIRCOUTCOMES.116.003863.

  5. Berge CA, Eskerud I, Almeland EB, Larsen TH, Pedersen ER, Rotevatn S et al. Relationship between hypertension and non-obstructive coronary artery disease in chronic coronary syndrome (the NORIC registry). PLoS One. 2022; 17 (1): e0262290. doi: 10.1371/journal.pone.0262290.

  6. Eskerud I, Gerdts E, Larsen TH, Lonnebakken MT. Left ventricular hypertrophy contributes to Myocardial Ischemia in Non-obstructive Coronary Artery Disease (the MicroCAD study). Int J Cardiol. 2019; 286: 1-6. doi: 10.1016/j.ijcard.2019.03.059.

  7. Padro T, Manfrini O, Bugiardini R, Canty J, Cenko E, De Luca G et al. ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on 'coronary microvascular dysfunction in cardiovascular disease'. Cardiovasc Res. 2020; 116 (4): 741-755. doi: 10.1093/cvr/cvaa003.

  8. Lonnebakken MT, Eskerud I, Larsen TH, Midtbo HB, Kokorina MV, Gerdts E. Impact of aortic stiffness on myocardial ischaemia in non-obstructive coronary artery disease. Open Heart. 2019; 6 (1): e000981. doi: 10.1136/openhrt-2018-000981.

  9. Mehilli J, Presbitero P. Coronary artery disease and acute coronary syndrome in women. Heart. 2020; 106 (7): 487-492. doi: 10.1136/heartjnl-2019-315555.

  10. Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM et al. Contemporary diagnosis and management of patients with myocardial infarction in the absence of obstructive coronary artery disease: a scientific statement from the American Heart Association. Circulation. 2019; 139 (18): e891-e908. doi: 10.1161/CIR.0000000000000670.

  11. Mygind ND, Michelsen MM, Pena A, Frestad D, Dose N, Aziz A et al. Coronary microvascular function and cardiovascular risk factors in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study. J Am Heart Assoc. 2016; 5 (3): e003064. doi: 10.1161/JAHA.115.003064.

  12. Nishimiya K, Suda A, Fukui K, Hao K, Takahashi J, Matsumoto Y et al. Prognostic links between OCT-delineated coronary morphologies and coronary functional abnormalities in patients with INOCA. JACC Cardiovasc Intervent. 2021; 14 (6): 606-618. doi: 10.1016/j.jcin.2020.12.025.

  13. Pauly DF, Johnson BD, Anderson RD, Handberg EM, Smith KM, Cooper-DeHoff RM et al. In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: A double-blind randomized study from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE). Am Heart J. 2011; 162 (4): 678-684. doi: 10.1016/j.ahj.2011.07.011.

  14. Schwartzkopff B, Brehm M, Mundhenke M, Strauer BE. Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease. Hypertension. 2000; 36 (2): 220-225. doi: 10.1161/01.HYP.36.2.220.

  15. Lindahl B, Baron T, Erlinge D, Hadziosmanovic N, Nordenskjold AM, Gard A et al. Medical therapy for secondary prevention and long-term outcome in patients with myocardial infarction with non-obstructive coronary artery disease. Circulation. 2017; 135 (16): 1481-1489. doi: 10.1161/CIRCULATIONAHA.116.026336.



AFFILIATIONS

1 Cardiologist, Master of Science, Member of the Chapter on Cardiopathies in Women, and Treasurer of ANCAM. Mexico.

2 Interventional Cardiologist, UMAE. Specialty Hospital No. 14, Veracruz, Ver.

3 Cardiologist Echocardiographer, Division of Cardiology, UMAE Cardiology Hospital, Century National Medical Center XXI, IMSS. Mexico City, Mexico.



CORRESPONDENCE

Alejandra Madrid-Miller. E-mail: ammiller@live.com.mx


2020     |     www.medigraphic.com