Publications by authors named "Puja K Mehta"

114 Publications

Socioeconomic characteristics of African American women attending community blood pressure screenings.

Am Heart J Plus 2022 Jan 23;13. Epub 2022 Mar 23.

Emory University School of Medicine, Division of Cardiology, 137 Johnson Ferry Rd. Ste. 1200, Marietta, GA 30068, United States of America.

Study Objective: To examine the associations of education and income and blood pressure (BP) in a socioeconomically diverse cohort of African-American (AA) women attending community BP screenings.

Design Setting And Participants: This cross-sectional analysis used data from AA women ( = 972) 53 ± 14 years, enrolled between 2015 and 2019 in the 10,000-women hypertension community screening project in the metropolitan Atlanta area. OLS linear regression were used to examine the associations between SES (education and income) and BP after adjusting for age, body mass index (BMI), smoking, and lipids.

Main Outcomes And Measures: Outcomes were systolic and diastolic BP (SBP, DBP). Measures of SES included education [high school ≤(HS), some college, and ≥college] and income-[<$24,000, $24,000-<$48,000, $48,000-$96,000, and ≥$96,000]. Sociodemographics, health history, anthropometrics and point of care non-fasting lipids were obtained.

Results: Compared to women earning <$24,000, an income of ≥$96,000 (β = -5.7 mmHg, 95% CI: -9.9, -1.5, = .01) was associated with a lower SBP in the minimally adjusted model. Subsequent adjustment for cardiovascular risk factors attenuated the association and was no longer significant. College and above versus ≤HS education was associated with a higher DBP in the minimally (ß = 2.7 mmHg, 95% CI: 0.2, 5.2, = .03) and fully adjusted models (ß = 3.4 mmHg, 95% CI: 0.2, 6.5, = .04).

Conclusion: Income of ≥$96,000 was associated with a lower SBP while a college and above education was associated with a higher DBP. Findings underscore the need for increased cardiovascular risk awareness and education targeting higher SES AA women attending community BP screenings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahjo.2022.100123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014812PMC
January 2022

Evaluation and management of blood lipids through a woman's life cycle.

Am J Prev Cardiol 2022 Jun 13;10:100333. Epub 2022 Mar 13.

Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

There are currently no sex-specific guidelines for evaluation and management of blood lipids. While previous guidelines acknowledge sex-specific risk enhancing factors for lipid management in women for CVD prevention, this review focuses on how lipids are impacted during normal hormonal changes throughout a woman's life cycle- during adolescence, pre-pregnancy, pregnancy, pre- and perimenopause, menopause, and at older ages. In this review, the authors focus on management of primary prevention of CVD by examining sex-specific cardiovascular risk factors at each stage and pay special attention to statin use, statin side effects and non-statin therapies. Women need to understand their personalized cholesterol goals and ally with their clinicians to ensure successful management. Additionally, we highlight the biases that exist when treating dyslipidemia in women and the special care clinicians should take to ensure appropriate and aggressive therapies are made available to female patients. Finally, the authors recommend future research should focus on increasing enrollment of women in lipid trials. This is of paramount importance in discovering sex-specific difference in lipid management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajpc.2022.100333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956895PMC
June 2022

Cardiovascular Implications of Immune Disorders in Women.

Circ Res 2022 02 17;130(4):593-610. Epub 2022 Feb 17.

Department of Medicine, Division of Infectious Diseases (C.A.M., L.F.C., I.O., C.D.L.), Emory University School of Medicine, Atlanta, GA.

Immune responses differ between men and women, with women at higher risk of developing chronic autoimmune diseases and having more robust immune responses to many viruses, including HIV and hepatitis C virus. Although immune dysregulation plays a prominent role in chronic systemic inflammation, a key driver in the development of atherosclerotic cardiovascular disease (ASCVD), standard ASCVD risk prediction scores underestimate risk in populations with immune disorders, particularly women. This review focuses on the ASCVD implications of immune dysregulation due to disorders with varying global prevalence by sex: autoimmune disorders (female predominant), HIV (male-female equivalent), and hepatitis C virus (male predominant). Factors contributing to ASCVD in women with immune disorders, including traditional risk factors, dysregulated innate and adaptive immunity, sex hormones, and treatment modalities, are discussed. Finally, the need to develop new ASCVD risk stratification tools that incorporate variables specific to populations with chronic immune disorders, particularly in women, is emphasized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCRESAHA.121.319877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869407PMC
February 2022

Somatic Versus Cognitive Depressive Symptoms as Predictors of Coronary Artery Disease among Women with Suspected Ischemia: The Women's Ischemia Syndrome Evaluation.

Heart Mind (Mumbai) 2021 Oct-Dec;5(4):112-118. Epub 2021 Nov 30.

Psychology Service, VA San Diego Healthcare System, San Diego, California.

Background: Depression is an established predictor of coronary artery disease (CAD) progression and mortality. "Somatic" symptoms of depression such as fatigue and sleep impairment overlap with symptoms of CAD and independently predict CAD events. Differentiating between "somatic" and "cognitive" depressive symptoms in at-risk patients may improve our understanding of the relationship between depression and CAD.

Methods: The study utilized data from the Women's Ischemia Syndrome Evaluation. Participants ( = 641; mean age = 58.0 [11.4] years) were enrolled to evaluate chest pain or suspected myocardial ischemia. They completed a battery of symptom and psychological questionnaires (including the Beck Depression Inventory [BDI]) at baseline, along with quantitative coronary angiography and other CAD diagnostic procedures. The BDI provided scores for total depression and for cognitive and somatic depressive symptom subscales.

Results: Two hundred and fourteen (33.4%) women met criteria for obstructive CAD. Logistic regression models were used to examine relationships between depression symptoms and obstructive CAD. Neither BDI total scores (odds ratio [OR] =1.02, 95% confidence interval [CI], 0.99-1.05, = 0.053) nor BDI cognitive scores (OR = 1.02, 95% CI, 1.00-1.04, = 0.15) predicted CAD status. BDI somatic symptom scores, however, significantly predicted CAD status and remained statistically significant after controlling for age, race, and education (OR = 1.06, 95% CI, 1.01-1.12, = 0.02).

Conclusion: Among women with suspected myocardial ischemia, somatic but not cognitive depressive symptoms predicted an increased risk of obstructive CAD determined by coronary angiography. Consistent with prior reports, these results suggest a focus on somatic rather than cognitive depressive symptoms could offer additional diagnostic information.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/hm.hm_34_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713564PMC
November 2021

Ischemia and no obstructive coronary arteries in patients with stable ischemic heart disease.

Int J Cardiol 2022 Feb 11;348:1-8. Epub 2021 Dec 11.

Department of Radiology, Weill-Cornell Medical College, New York, NY, United States of America.

A large proportion of patients with suspected obstructive coronary artery disease (CAD) is found to have ischemia with no obstructive coronary artery disease (INOCA). Based on current evidence, these patients are at increased risk of adverse cardiovascular events, even though they have no obstructive CAD. Importantly, INOCA is associated with recurrent clinical presentations with chest pain, impaired functional capacity, reduced health-related quality of life, and high healthcare costs. Underlying coronary microvascular dysfunction (CMD), through endothelium-dependent and independent mechanisms contribute to these adverse outcomes in INOCA. While non-invasive and invasive diagnostic testing has typically focused on identification of obstructive CAD in symptomatic patients, functional testing to detect coronary epicardial and microvascular dysfunction should be considered in those with INOCA who have persistent angina. Current diagnostic methods to clarify functional abnormalities and treatment strategies for epicardial and/or microvascular dysfunction in INOCA are reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2021.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779638PMC
February 2022

Gender-Related Differences in Chest Pain Syndromes in the Frontiers in CV Medicine Special Issue: Sex & Gender in CV Medicine.

Front Cardiovasc Med 2021 17;8:744788. Epub 2021 Nov 17.

Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA, United States.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality among both women and men, yet women continue to have delays in diagnosis and treatment. The lack of recognition of sex-specific biological and socio-cultural gender-related differences in chest pain presentation of CAD may, in part, explain these disparities. Sex and gender differences in pain mechanisms including psychological susceptibility, the autonomic nervous system (ANS) reactivity, and visceral innervation likely contribute to chest pain differences. CAD risk scores and typical/atypical angina characterization no longer appear relevant and should not be used in women and men. Women more often have ischemia with no obstructive CAD (INOCA) and myocardial infarction, contributing to diagnostic and therapeutic equipoise. Existing knowledge demonstrates that chest pain often does not relate to obstructive CAD, suggesting a more thoughtful approach to percutaneous coronary intervention (PCI) and medical therapy for chest pain in stable obstructive CAD. Emerging knowledge regarding the central and ANS and visceral pain processing in patients with and without angina offers explanatory mechanisms for chest pain and should be investigated with interdisciplinary teams of cardiologists, neuroscientists, bio-behavioral experts, and pain specialists. Improved understanding of sex and gender differences in chest pain, including biological pathways as well as sociocultural contributions, is needed to improve clinical care in both women and men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.744788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635525PMC
November 2021

Transcutaneous Cervical Vagal Nerve Stimulation in Patients with Posttraumatic Stress Disorder (PTSD): A Pilot Study of Effects on PTSD Symptoms and Interleukin-6 Response to Stress.

J Affect Disord Rep 2021 Dec 10;6. Epub 2021 Jul 10.

School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia.

Background: Posttraumatic stress disorder (PTSD) is a highly disabling condition associated with alterations in multiple neurobiological systems, including increases in inflammatory and sympathetic function, responsible for maintenance of symptoms. Treatment options including medications and psychotherapies have limitations. We previously showed that transcutaneous Vagus Nerve Stimulation (tcVNS) blocks inflammatory (interleukin (IL)-6) responses to stress in PTSD. The purpose of this study was to assess the effects of tcVNS on PTSD symptoms and inflammatory responses to stress.

Methods: Twenty patients with PTSD were randomized to double blind active tcVNS (N=9) or sham (N=11) stimulation in conjunction with exposure to personalized traumatic scripts immediately followed by active or sham tcVNS and measurement of IL-6 and other biomarkers of inflammation. Patients then self administered active or sham tcVNS twice daily for three months. PTSD symptoms were measured with the PTSD Checklist (PCL) and the Clinician Administered PTSD Scale (CAPS), clinical improvement with the Clinical Global Index (CGI) and anxiety with the Hamilton Anxiety Scale (Ham-A) at baseline and one-month intervals followed by a repeat of measurement of biomarkers with traumatic scripts. After three months patients self treated with twice daily open label active tcVNS for another three months followed by assessment with the CGI.

Results: Traumatic scripts increased IL-6 in PTSD patients, an effect that was blocked by tcVNS (p<.05). Active tcVNS treatment for three months resulted in a 31% greater reduction in PTSD symptoms compared to sham treatment as measured by the PCL (p=0.013) as well as hyperarousal symptoms and somatic anxiety measured with the Ham-A p<0.05). IL-6 increased from baseline in sham but not tcVNS. Open label tcVNS resulted in improvements measured with the CGI compared to the sham treatment period p<0.05).

Conclusions: These preliminary results suggest that tcVNS reduces inflammatory responses to stress, which may in part underlie beneficial effects on PTSD symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jadr.2021.100190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580056PMC
December 2021

Coronary endothelial dysfunction appears to be a manifestation of a systemic process: A report from the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) study.

PLoS One 2021 27;16(9):e0257184. Epub 2021 Sep 27.

Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America.

Background: Coronary microvascular dysfunction (CMD) is prevalent in symptomatic women with ischemia but no obstructive coronary artery disease (INOCA). Urine albumin-creatinine ratio (UACR) is a measure of renal microvascular endothelial dysfunction. Both are predictors of adverse cardiovascular events. It is unknown if CMD could be a manifestation of a systemic process. We evaluated the relationship between renal microvascular dysfunction and CMD as measured by invasive coronary function testing (CFT).

Methods And Results: We measured urine albumin and creatinine to provide UACR in 152 women enrolled in the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study (2008-2015) with suspected INOCA who underwent CFT. Invasive CFT measures of endothelial and non-endothelial dependent coronary microvascular function were obtained. Subjects were divided into those with detectable (≥20 mg/g) and undetectable urine albumin (<20 mg/g). The group mean age was 54 ± 11 years, with a moderate cardiac risk factor burden including low diabetes prevalence, and a mean UACR of 12 ± 55 mg/g (range 9.5-322.7 mg/g). Overall, coronary endothelial-dependent variables (change in coronary blood flow and coronary diameter in response to cold pressor testing) had significant inverse correlations with log UACR (r = -0.17, p = 0.05; r = -0.18, p = 0.03, respectively).

Conclusions: Among women with INOCA and relatively low risk factor including diabetes burden, renal microvascular dysfunction, measured by UACR, is related to coronary endothelial-dependent CMD. These results suggest that coronary endothelial-dependent function may be a manifestation of a systemic process. Enhancing efferent arteriolar vasodilatation in both coronary endothelial-dependent function and renal microvascular dysfunction pose potential targets for investigation and treatment.

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00832702.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257184PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476029PMC
November 2021

Brain-heart connections in stress and cardiovascular disease: Implications for the cardiac patient.

Atherosclerosis 2021 07 30;328:74-82. Epub 2021 May 30.

Emory Clinical Cardiovascular Research Institute, Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA. Electronic address:

The influence of psychological stress on the physiology of the cardiovascular system, and on the etiology and outcomes of cardiovascular disease (CVD) has been the object of intense investigation. As a whole, current knowledge points to a "brain-heart axis" that is especially important in individuals with pre-existing CVD. The use of acute psychological stress provocation in the laboratory has been useful to clarify the effects of psychological stress on cardiovascular physiology, immune function, vascular reactivity, myocardial ischemia, neurobiology and cardiovascular outcomes. An emerging paradigm is that dynamic perturbations of physiological and molecular pathways during stress or negative emotions are important in influencing cardiovascular outcomes, and that some patient subgroups, such as women, patients with an early-onset myocardial infarction, and patients with adverse psychosocial exposures, may be at especially high risk for these effects. This review summarizes recent knowledge on mind-body connections in CVD among cardiac patients and highlights important pathways of risk which could become the object of future intervention efforts. As a whole, this research suggests that an integrated study of mind and body is necessary to fully understand the determinants and consequences of CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2021.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254768PMC
July 2021

The black box of coronary microcirculation: Is it at the tip of the finger?

Int J Cardiol 2021 08 1;336:29-31. Epub 2021 Jun 1.

Emory Women's Heart Center and Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States of America.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2021.05.049DOI Listing
August 2021

Clinical characteristics and prognosis of patients with microvascular angina: an international and prospective cohort study by the Coronary Vasomotor Disorders International Study (COVADIS) Group.

Eur Heart J 2021 11;42(44):4592-4600

Department of Cardiology, Cedars-Sinai Medical Center, Barbra Streisand Women's Heart Center, Smidt Heart Institute, Los Angeles, CA, USA.

Aims: To provide multi-national, multi-ethnic data on the clinical characteristics and prognosis of patients with microvascular angina (MVA).

Methods And Results: The Coronary Vasomotor Disorders International Study Group proposed the diagnostic criteria for MVA. We prospectively evaluated the clinical characteristics of patients according to these criteria and their prognosis. The primary endpoint was the composite of major cardiovascular events (MACE), verified by institutional investigators, which included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. During the period from 1 July 2015 to 31 December 2018, 686 patients with MVA were registered from 14 institutes in 7 countries from 4 continents. Among them, 64% were female and the main ethnic groups were Caucasians (61%) and Asians (29%). During follow-up of a median of 398 days (IQR 365-744), 78 MACE occurred (6.4% in men vs. 8.6% in women, P = 0.19). Multivariable Cox proportional hazard analysis disclosed that hypertension and previous history of coronary artery disease (CAD), including acute coronary syndrome and stable angina pectoris, were independent predictors of MACE. There was no sex or ethnic difference in prognosis, although women had lower Seattle Angina Questionnaire scores than men (P < 0.05).

Conclusions: This first international study provides novel evidence that MVA is an important health problem regardless of sex or ethnicity that a diagnosis of MVA portends a substantial risk for MACE associated with hypertension and previous history of CAD, and that women have a lower quality of life than men despite the comparable prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633728PMC
November 2021

Berries and Their Polyphenols as a Potential Therapy for Coronary Microvascular Dysfunction: A Mini-Review.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Department of Nutrition, Georgia State University, Atlanta, GA 30302, USA.

Ischemia with no obstructive coronary artery disease (INOCA) is a common diagnosis with a higher prevalence in women compared to men. Despite the absence of obstructive coronary artery disease and no structural heart disease, INOCA is associated with major adverse cardiovascular outcomes as well a significant contributor to angina and related disability. A major feature of INOCA is coronary microvascular dysfunction (CMD), which can be detected by non-invasive imaging and invasive coronary physiology assessments in humans. CMD is associated with epicardial endothelial-dependent and -independent dysfunction, diffuse atherosclerosis, and left-ventricular hypertrophy, all of which lead to insufficient blood flow to the myocardium. Inflammatory and oxidative stress signaling, upregulation of the renin-angiotensin-aldosterone system and adrenergic receptor signaling are major drivers of CMD. Treatment of CMD centers around addressing cardiovascular risk factors; however, there are limited treatment options for those who do not respond to traditional anti-anginal therapies. In this review, we highlight the ability of berry-derived polyphenols to modulate those pathways. The evidence supports the need for future clinical trials to investigate the effectiveness of berries and their polyphenols in the treatment of CMD in INOCA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22073373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036956PMC
March 2021

Alterations in Insulin Levels in Adults with Prenatal Alcohol Exposure.

Alcohol Clin Exp Res 2021 03 24;45(3):500-506. Epub 2021 Feb 24.

Department of Psychiatry and Behavioral Science, Emory University School of Medicine, Atlanta, GA, USA.

Objective: Evidence suggests that prenatal alcohol exposure (PAE) may adversely impact insulin production and signaling but there is limited information on the range of these effects and their future health consequences.

Method: A prospective cohort of predominantly African-American individuals identified while in utero and followed into adulthood were used to evaluate differences in various indicators of diabetes, including fasting plasma glucose, hemoglobin A1c (HbA1c), and insulin levels. The homeostatic model assessment of insulin resistance (HOMA-IR) was also computed. Body mass index (BMI) was calculated and normal defined as < 25 kg/m . Participants were categorized as having PAE (n = 39) if their mothers drank at least 1 ounce of absolute alcohol per week or more during the 1 trimester of pregnancy and as Controls (n = 22) if their mothers reported abstaining from alcohol consumption during pregnancy.

Results: Mean age of the sample was 36.0 ± 1.5 years. Indices of glucose metabolism, including fasting plasma glucose and hemoglobin A1c levels, did not vary by group status but insulin levels and HOMA-IR values varied by group status and BMI level. PAE individuals with a normal BMI had lower insulin levels than Controls. However, in PAE subjects, there was a steeper increase in insulin levels relative to their BMI than in Control subjects. A cluster of 5 PAE cases had low levels of insulin and 4 of the 5 had severe cognitive impairment.

Conclusions: The bidirectional effects on insulin level and insulin resistance associated with PAE may indicate differential rates of diabetes disease impact or differential PAE impact in the brain and peripheral areas involved in insulin production and signaling. These alterations may contribute to the metabolic disease risk associated with PAE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acer.14559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717214PMC
March 2021

Ivabradine in Cardiovascular Disease Management Revisited: a Review.

Cardiovasc Drugs Ther 2021 10 7;35(5):1045-1056. Epub 2021 Jan 7.

Division of Cardiology, Department of Medicine, Albany Medical College and Albany Medical Center, 47 New Scotland Ave, Albany, NY, 12208, USA.

Ivabradine is a unique agent that is distinct from beta-blockers and calcium channel blockers as it reduces heart rate without affecting myocardial contractility or vascular tone. Ivabradine is a use-dependent inhibitor targeting the sinoatrial node. It is approved for use in the United States as an adjunct therapy for heart rate reduction in patients with heart failure with reduced ejection fraction. In this scenario, ivabradine has demonstrated improved clinical outcomes due to reduction in heart failure readmissions. However, there has been conflicting evidence from prospective studies and randomized controlled trials for its use in stable ischemic heart disease regarding efficacy in symptom reduction and mortality benefit. Ivabradine may also play a role in the treatment of patients with inappropriate sinus tachycardia, who often cannot tolerate beta-blockers and/or calcium channel blockers. In this review, we highlight the evidence for the nuances of using ivabradine in heart failure, stable ischemic heart disease, and inappropriate sinus tachycardia to raise awareness for its vital role in the treatment of select populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10557-020-07124-4DOI Listing
October 2021

Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis: The MARINA Randomized, Double-Blinded, Controlled Pilot Trial.

Circ Cardiovasc Interv 2020 12 4;13(12):e008204. Epub 2020 Dec 4.

Andreas Gruentzig Cardiovascular Center, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (J.-S.K., O.Y.H., P.E., R.R., M.R., S.K., S.G., H.H., N.S., G.M.B., C.L., P.K.M., A.A.Q., H.S.).

Background: Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease.

Methods: In this randomized, double-blinded, placebo-controlled pilot trial, 26 patients with angina once weekly or more, abnormal stress test, and nonobstructive coronary artery disease (<50% stenosis by angiography and fractional flow reserve >0.80) were randomized 1:1 to ranolazine or placebo for 12 weeks. Primary end point was ΔSeattle Angina Questionnaire (SAQ) angina frequency score. Baseline and 3 months follow-up SAQ, Duke Activity Status Index scores along with invasive fractional flow reserve, coronary flow reserve (CFR), hyperemic myocardial resistance, and cardiopulmonary exercise testing measurements were performed.

Results: No significant differences in ΔSAQ angina frequency scores (=0.53) or Duke Activity Status Index (=0.76) were observed between ranolazine versus placebo, although patients on ranolazine had lesser improvement in SAQ physical limitation scores (=0.02) compared with placebo at 3 months. There were no significant differences in ΔCFR or Δhyperemic myocardial resistance between ranolazine and placebo groups. Patients treated with ranolazine, compared with placebo, had no significant improvement in maximum rate of oxygen consumption measured during incremental exercise (VO max) and peak metabolic equivalents of task. Interestingly, in the ranolazine group, patients with baseline CFR<2.0 demonstrated greater gain in CFR compared with those with baseline CFR≥2.0 (=0.02).

Conclusions: Ranolazine did not demonstrate improvement in SAQ angina frequency score, invasive microvascular function, or peak metabolic equivalent compared with placebo at 3 months. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147067.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008204DOI Listing
December 2020

N-Terminal pro-B-type natriuretic peptide and coronary microvascular dysfunction in women with preserved ejection fraction: A report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study.

PLoS One 2020 3;15(12):e0243213. Epub 2020 Dec 3.

Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, United States of America.

Background: Women with symptoms and signs of ischemia, preserved left ventricular ejection fraction (LVEF), and no obstructive coronary artery disease (CAD), often have coronary microvascular dysfunction (CMD), and are at risk of future heart failure with preserved ejection fraction (HFpEF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used to evaluate HF and myocardial ischemia. Relationships between NT-proBNP and CMD are not well defined in this population.

Methods: We evaluated resting NT-proBNP levels in 208 women with symptoms and signs of ischemic heart disease, preserved LVEF and no obstructive CAD undergoing clinically indicated invasive coronary flow reserve (CFR) as a measure of CMD-related ischemia and resting left ventricular end-diastolic pressure (LVEDP). Chi-square testing was used for categorical variables and ANOVA or Kruskal-Wallis tests were used for continuous variables.

Results: Overall, 79% had an elevated resting LVEDP, and mean NT-proBNP was 115 ± 158 pg/mL. NT-proBNP levels correlated directly with age (r = 0.28, p = <0.0001), and indirectly with body mass index (r = -0.21, p = 0.0006), but did not independently associate with CFR. When stratified by NT-proBNP thresholds, higher NT-proBNP was initially associated with lower CFR, which did not persist with adjustment for multiple testing (p = 0.01 and 0.36, respectively).

Conclusion: Among women with symptoms and signs of ischemia, preserved LVEF, no obstructive CAD, and undergoing clinically indicated functional coronary angiography (FCA) for suspected CMD, while a majority had elevated resting LVEDP, we failed to find an independent association between CFR and NT-proBNP, although stratified clinical thresholds may relate to lower CFR. Further work is needed to investigate if these findings support the hypothesis that CMD-related ischemia may be a precursor to HFpEF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243213PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714343PMC
January 2021

Coronary Optical Coherence Tomography and Cardiac Magnetic Resonance Imaging to Determine Underlying Causes of Myocardial Infarction With Nonobstructive Coronary Arteries in Women.

Circulation 2021 02 14;143(7):624-640. Epub 2020 Nov 14.

University of Florida, Gainesville (K.P.).

Background: Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 6% to 15% of myocardial infarctions (MIs) and disproportionately affects women. Scientific statements recommend multimodality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance (CMR) imaging to assess mechanisms of MINOCA.

Methods: In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of myocardial infarction. If invasive coronary angiography revealed <50% stenosis in all major arteries, multivessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and nonischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible.

Results: Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intraplaque cavity, or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% (62/116) of participants undergoing CMR. A nonischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome, or nonischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% (98/116) of the women with multimodality imaging, higher than with OCT alone (<0.001) or CMR alone (=0.001). An ischemic cause was identified in 63.8% of women with MINOCA (74/116), a nonischemic cause was identified in 20.7% (24/116) of the women, and no mechanism was identified in 15.5% (18/116).

Conclusions: Multimodality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, 75.5% of which were ischemic and 24.5% of which were nonischemic, alternate diagnoses to myocardial infarction. Identification of the cause of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02905357.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627695PMC
February 2021

Association of Early-Life Trauma and Risk of Adverse Cardiovascular Outcomes in Young and Middle-aged Individuals With a History of Myocardial Infarction.

JAMA Cardiol 2020 Nov 13. Epub 2020 Nov 13.

Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

Importance: Compared with older patients, young adults with a history of myocardial infarction (MI) tend to have a higher burden of psychosocial adversity. Exposure to early-life stressors may contribute to the risk of adverse outcomes in this patient population, potentially through inflammatory pathways.

Objective: To investigate the association of early-life trauma with adverse events and examine whether inflammation plays a role.

Design, Setting, And Participants: This cohort study included patients aged 18 to 60 years with a verified history of MI in the past 8 months from a university-affiliated hospital network. Baseline data were collected from June 2011 to March 2016, and follow-up data were obtained through July 2019. Analysis began September 2019.

Exposures: Early-life trauma was assessed using the Early Trauma Inventory-Self Report short form (ETI-SR-SF), both as a continuous and as a binary variable at the threshold of a score of 7 or higher. Inflammatory biomarkers, interleukin 6, and C-reactive protein were obtained at baseline.

Main Outcomes And Measures: A composite end point of recurrent MI, stroke, heart failure hospitalization, and cardiovascular death over a median 3-year follow-up.

Results: Of 300 patients, the mean (SD) age was 51 (7) years, 198 (66%) were African American, and 150 (50%) were women. Compared with participants with MI with an ETI-SR-SF score less than 7, those with a score of 7 or higher had higher levels of interleukin 6 and C-reactive protein at baseline. Compared with participants with an ETI-SR-SF score less than 7, those with a score of 7 or higher were at a greater risk for adverse outcomes, with a hazards ratio of 2.3 (95% CI, 1.3-3.9). Results remained consistent in multivariable analysis. Further adjustment for C-reactive protein rendered the results no longer statistically significant. Early-life trauma displayed a dose-dependent response when analyzed as a continuous variable and by quartiles.

Conclusions And Relevance: Early-life trauma is an independent risk factor for adverse outcomes in young and middle-aged individuals with a history of MI. Neurobiological mechanisms leading to lifetime activation of systemic inflammatory cascades may be implicated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2020.5749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666433PMC
November 2020

Takotsubo Syndrome in Patients with COVID-19: a Systematic Review of Published Cases.

SN Compr Clin Med 2020 6;2(11):2102-2108. Epub 2020 Oct 6.

Division of Cardiology, Atlanta VA Medical Center, Decatur, GA USA.

Takotsubo syndrome (TTS) is caused by catecholamine surge, which is also observed in COVID-19 disease due to the cytokine storm. We performed a systematic literature search using PubMed/Medline, SCOPUS, Web of Science, and Google Scholar databases to identify COVID-19-associated TTS case reports and evaluated patient-level demographics, clinical attributes, and outcomes. There are 12 cases reported of TTS associated with COVID-19 infection with mean age of 70.8 ± 15.2 years (range 43-87 years) with elderly (66.6% > 60 years) female (66.6%) majority. The time interval from the first symptom to TTS was 8.3 ± 3.6 days (range 3-14 days). Out of 12 cases, 7 reported apical ballooning, 4 reported basal segment hypo/akinesia, and 1 reported median TTS. Out of 12 cases, during hospitalization, data on left ventricular ejection fraction (LVEF) was reported in only 9 of the cases. The mean LVEF was 40.6 ± 9.9% (male, 46.7 ± 5.7%, and female, 37.7 ± 10.6%). Troponin was measured in all 12 cases and was elevated in 11 (91.6%) without stenosis on coronary angiography except one. Out of 11 cases, 6 developed cardiac complications with 1 case each of cardiac tamponade, heart failure, myocarditis, hypertensive crisis, and cardiogenic shock in 2. Five patients required intubation, 1 patient required continuous positive airway pressure, and 1 patient required venovenous extracorporeal membrane oxygenation. The outcome was reported in terms of recovery in 11 (91.6%) out of 12 cases, and a successful recovery was noted in 10 (90.9%) cases. COVID-19-related TTS has a higher prevalence in older women. Despite a lower prevalence of cardiac comorbidities in COVID-19 patients, direct myocardial injury, inflammation, and stress may contribute to TTS with a high complication rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s42399-020-00557-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538054PMC
October 2020

Coronary Vascular Function and Cardiomyocyte Injury: A Report From the WISE-CVD.

Arterioscler Thromb Vasc Biol 2020 12 8;40(12):3015-3021. Epub 2020 Oct 8.

Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA (J.W., O.Q., B.A., B.S., T.D.H., J.V.E., C.N.B.M.).

Objective: Women with symptoms or signs of myocardial ischemia but no obstructive coronary artery disease (INOCA) often have coronary vascular dysfunction and elevated risk for adverse cardiovascular events. We hypothesized that u-hscTnI (ultra-high-sensitivity cardiac troponin I), a sensitive indicator of ischemic cardiomyocyte injury, is associated with coronary vascular dysfunction in women with INOCA. Approach and Results: Women (N=263) with INOCA enrolled in the WISE-CVD study (Women's Ischemic Syndrome Evaluation-Coronary Vascular Dysfunction) underwent invasive coronary vascular function testing and u-hscTnI measurements (Simoa HD-1 Analyzer; Quanterix Corporation, Lexington, MA). Logistic regression models, adjusted for traditional cardiovascular risk factors were used to evaluate associations between u-hscTnI and coronary vascular function. Women with coronary vascular dysfunction (microvascular constriction and limited coronary epicardial dilation) had higher plasma u-hscTnI levels (both =0.001). u-hscTnI levels were associated with microvascular constriction (odds ratio, 1.38 per doubling of u-hscTnI [95% CI, 1.03-1.84]; =0.033) and limited coronary epicardial dilation (odds ratio, 1.37 per doubling of u-hscTnI [95% CI, 1.04-1.81]; =0.026). u-hscTnI levels were not associated with microvascular dilation or coronary epicardial constriction.

Conclusions: Our findings indicate that higher u-hscTnI is associated with coronary vascular dysfunction in women with INOCA. This suggests that ischemic cardiomyocyte injury in the setting of coronary vascular dysfunction has the potential to contribute to adverse cardiovascular outcomes observed in these women. Additional studies are needed to confirm and investigate mechanisms underlying these findings in INOCA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00832702.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.120.314260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079158PMC
December 2020

Sex differences in the inflammatory response to stress and risk of adverse cardiovascular outcomes among patients with coronary heart disease.

Brain Behav Immun 2020 11 8;90:294-302. Epub 2020 Sep 8.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States; Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States.

Stress may contribute to progression of coronary heart disease (CHD) through inflammation, especially among women. Thus, we sought to examine whether increased inflammatory response to stress among patients with CHD is associated with a greater risk of cardiovascular events and whether this risk is higher in women. We examined inflammatory biomarkers known to increase with mental stress (speech task), including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and matrix metallopeptidase-9 (MMP-9) among 562 patients with stable CHD. Inflammatory response, the difference between post-stress and resting values, was examined as a predictor of major adverse cardiovascular events (MACE) using subdistribution hazards models for competing risks adjusting for demographics, cardiovascular risk factors, and medications. MACE was defined as a composite endpoint of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure. All biomarkers were standardized. The mean age was 63 years (range 34-79) and 24% were women. During a median follow-up of 3 years, 71 patients experienced MACE. Overall, there was no significant association between inflammatory response to stress and risk of MACE, but there were sex-based interactions for IL-6 (p = 0.001) and MCP-1 (p = 0.01). The risk of MACE increased 56% (HR: 1.56; 95% CI: 1.21, 2.01; p = 0.001) and 30% (HR: 1.30; 95% 1.09, 1.55; p = 0.004) for each standard deviation increase in IL-6 and MCP-1 response to mental stress for women, respectively, while there was no association among men. Increased inflammation in response to stress is associated with future adverse cardiovascular outcomes among women with CHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbi.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872132PMC
November 2020

Functional coronary angiography in symptomatic patients with no obstructive coronary artery disease.

Catheter Cardiovasc Interv 2021 11 9;98(5):827-835. Epub 2020 Sep 9.

Division of Cardiology, Department of Internal Medicine, Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia, USA.

Background: Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy.

Methods: 163 symptomatic patients with ≤50% diameter stenosis and fractional flow reserve (FFR) > 0.8 underwent endothelium-dependent epicardial and microvascular function after intracoronary acetylcholine (10  M, 81 mcg over 3 minutes). Endothelium-independent function was assessed using coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) after intravenous adenosine (140 ug/kg/min). Coronary microvascular dysfunction (CMD) was defined as CFR < 2.5, HMR ≥2, or ≤50% change in coronary blood flow with acetylcholine (CBF ).

Results: Seventy-two percent had endothelial-dependent epicardial dysfunction (response to ACH: % ∆ in coronary artery diameter and ∆%CBF ) and 92% had CMD. Among CMD patients, 65% had CFR < 2.5, 35% had HMR ≥2, and 60% had CBF change ≤50%. CFR modestly correlated with HMR (r = -0.38, p < .0001). Among patients with normal CFR, 26% had abnormal epicardial and 20% had abnormal microvascular endothelial dysfunction. Women had a lower CFR (p = .02), higher FFR (p = .03) compared to men. There were no differences in epicardial and microvascular function between patients with stable and unstable angina.

Conclusion: In patients with no obstructive CAD: CMD is prevalent, abnormal CFR does not correlate with epicardial or microvascular endothelial dysfunction, women have lower CFR, higher FFR but similar endothelial function compared to men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.29237DOI Listing
November 2021

Untargeted high-resolution plasma metabolomic profiling predicts outcomes in patients with coronary artery disease.

PLoS One 2020 18;15(8):e0237579. Epub 2020 Aug 18.

Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

Objective: Patients with CAD have substantial residual risk of mortality, and whether hitherto unknown small-molecule metabolites and metabolic pathways contribute to this risk is unclear. We sought to determine the predictive value of plasma metabolomic profiling in patients with CAD.

Approach And Results: Untargeted high-resolution plasma metabolomic profiling of subjects undergoing coronary angiography was performed using liquid chromatography/mass spectrometry. Metabolic features and pathways associated with mortality were identified in 454 subjects using metabolome-wide association studies and Mummichog, respectively, and validated in 322 subjects. A metabolomic risk score comprising of log-transformed HR estimates of metabolites that associated with mortality and passed LASSO regression was created and its performance validated. In 776 subjects (66.8 years, 64% male, 17% Black), 433 and 357 features associated with mortality (FDR-adjusted q<0.20); and clustered into 21 and 9 metabolic pathways in first and second cohorts, respectively. Six pathways (urea cycle/amino group, tryptophan, aspartate/asparagine, lysine, tyrosine, and carnitine shuttle) were common. A metabolomic risk score comprising of 7 metabolites independently predicted mortality in the second cohort (HR per 1-unit increase 2.14, 95%CI 1.62, 2.83). Adding the score to a model of clinical predictors improved risk discrimination (delta C-statistic 0.039, 95%CI -0.006, 0.086; and Integrated Discrimination Index 0.084, 95%CI 0.030, 0.151) and reclassification (continuous Net Reclassification Index 23.3%, 95%CI 7.9%, 38.2%).

Conclusions: Differential regulation of six metabolic pathways involved in myocardial energetics and systemic inflammation is independently associated with mortality in patients with CAD. A novel risk score consisting of representative metabolites is highly predictive of mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237579PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444579PMC
October 2020

Association Between Mental Stress-Induced Inferior Frontal Cortex Activation and Angina in Coronary Artery Disease.

Circ Cardiovasc Imaging 2020 08 10;13(8):e010710. Epub 2020 Aug 10.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (K.M., B.B.L., V.V., A.J.S.).

Background: The inferior frontal lobe is an important area of the brain involved in the stress response, and higher activation with acute mental stress may indicate a more severe stress reaction. However, it is unclear if activation of this region with stress correlates with angina in individuals with coronary artery disease.

Methods: Individuals with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors in conjunction with high resolution positron emission tomography imaging of the brain. Blood flow to the inferior frontal lobe was evaluated as a ratio compared with whole brain flow for each scan. Angina was assessed with the Seattle Angina Questionnaire's angina frequency subscale at baseline and 2 years follow-up.

Results: We analyzed 148 individuals with coronary artery disease (mean age [SD] 62 [8] years; 69% male, and 35.8% Black). For every doubling in the inferior frontal lobe activation, angina frequency was increased by 13.7 units at baseline ([Formula: see text], 13.7 [95% CI, 6.3-21.7]; =0.008) and 11.6 units during follow-up ([Formula: see text], 11.6 [95% CI, 4.1-19.2]; =0.01) in a model adjusted for baseline demographics. Mental stress-induced ischemia and activation of other brain pain processing regions (thalamus, insula, and amygdala) accounted for 40.0% and 13.1% of the total effect of inferior frontal lobe activation on angina severity, respectively.

Conclusions: Inferior frontal lobe activation with mental stress is independently associated with angina at baseline and during follow-up. Mental stress-induced ischemia and other pain processing brain regions may play a contributory role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCIMAGING.120.010710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422935PMC
August 2020

Temporal Trends in Angina, Myocardial Perfusion, and Left Ventricular Remodeling in Women With No Obstructive Coronary Artery Disease Over 1-Year Follow-Up: Results From WISE-CVD.

J Am Heart Assoc 2020 07 24;9(13):e016305. Epub 2020 Jun 24.

Barbra Streisand Women's Heart Center Cedars Sinai Smidt Heart Institute Los Angeles CA.

Background Women with ischemia and no obstructive coronary artery disease are increasingly recognized and found to be at risk for major adverse cardiovascular events. Methods and Results In 214 women with suspected ischemia and no obstructive coronary artery disease who completed baseline and 1-year follow-up vasodilatory stress cardiac magnetic resonance imaging, we investigated temporal trends in angina (Seattle Angina Questionnaire [SAQ]), myocardial perfusion reserve index, blood pressure, and left ventricular (LV) remodeling and function from baseline to 1-year follow-up and explored associations between these different parameters. We observed concordant positive trends in 4/5 SAQ domains, SAQ-7, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass-to-volume ratio. There was no association between SAQ-7 improvement and myocardial perfusion reserve index improvement over 1-year follow-up (=0.1). Higher indexed LV end-diastolic volume and time to peak filling rate at baseline were associated with increased odds of clinically relevant SAQ-7 improvement (odds ratio [OR], 1.05; 95% CI, 1.0-1.1; and OR, 2.40; 95% CI, 1.1-5.0, respectively). Hypertension was associated with decreased odds of SAQ-7 improvement (OR, 0.41; 95% CI, 0.19-0.91). Conclusions In women with ischemia and no obstructive coronary artery disease clinically treated with cardiac medications over 1 year, we observed concurrent temporal trends toward improvement in SAQ, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass-to volume ratio. We showed that abnormalities in LV morphology and diastolic function at baseline were predictive of clinically significant improvement in angina at follow-up, whereas history of hypertension was associated with lower odds. Future studies are needed to assess the mechanisms and treatments responsible for the improvements we observed. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02582021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.016305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670509PMC
July 2020

Higher Activation of the Rostromedial Prefrontal Cortex During Mental Stress Predicts Major Cardiovascular Disease Events in Individuals With Coronary Artery Disease.

Circulation 2020 08 11;142(5):455-465. Epub 2020 Jun 11.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (K.M., B.B.L., B.D.P., Z.A., Y.V.S., M.G., V.V., A.J.S.).

Background: Psychological stress is a risk factor for major adverse cardiovascular events (MACE) in individuals with coronary artery disease. Certain brain regions that control both emotional states and cardiac physiology may be involved in this relationship. The rostromedial prefrontal cortex (rmPFC) is an important brain region that processes stress and regulates immune and autonomic functions. Changes in rmPFC activity with emotional stress (reactivity) may be informative of future risk for MACE.

Methods: Participants with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors and simultaneous brain imaging with high-resolution positron emission tomography brain imaging. We defined high rmPFC activation as a difference between stress and control scans greater than the median value for the entire cohort. Interleukin-6 levels 90 minutes after stress, and high-frequency heart rate variability during stress were also assessed. We defined MACE as a composite of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure hospitalization.

Results: We studied 148 subjects (69% male) with mean±SD age of 62±8 years. After adjustment for baseline demographics, risk factors, and baseline levels of interleukin-6 and high-frequency heart rate variability, higher rmPFC stress reactivity was independently associated with higher interleukin-6 and lower high-frequency heart rate variability with stress. During a median follow-up of 3 years, 34 subjects (21.3%) experienced a MACE. Each increase of 1 SD in rmPFC activation with mental stress was associated with a 21% increase risk of MACE (hazard ratio, 1.21 [95% CI, 1.08-1.37]). Stress-induced interleukin-6 and high-frequency heart rate variability explained 15.5% and 32.5% of the relationship between rmPFC reactivity and MACE, respectively. Addition of rmPFC reactivity to conventional risk factors improved risk reclassification for MACE prediction, and C-statistic improved from 0.71 to 0.76 (=0.03).

Conclusions: Greater rmPFC stress reactivity is associated with incident MACE. Immune and autonomic responses to mental stress may play a contributory role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677173PMC
August 2020

Summary of Updated Recommendations for Primary Prevention of Cardiovascular Disease in Women: JACC State-of-the-Art Review.

J Am Coll Cardiol 2020 05;75(20):2602-2618

Rush Medical College, Rush University, Chicago, Illinois.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for women in the United States and worldwide. There has been no American College of Cardiology (ACC)/American Heart Association guideline update specifically for the prevention of CVD in women since 2011. Since then, the body of sex-specific data has grown, in addition to updated hypertension, cholesterol, diabetes, atrial fibrillation, and primary prevention guidelines. The ACC CVD in Women Committee undertook a review of the recent guidelines and major studies to summarize recommendations pertinent to women. In this update, the authors address special topics, particularly the risk factors and treatments that have led to some controversies and confusion. Specifically, sex-related risk factors, hypertension, diabetes, hyperlipidemia, anticoagulation for atrial fibrillation, use of aspirin, perimenopausal hormone therapy, and psychosocial issues are highlighted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2020.03.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328156PMC
May 2020

Oxidative Stress Is Associated With Diastolic Dysfunction in Women With Ischemia With No Obstructive Coronary Artery Disease.

J Am Heart Assoc 2020 05 7;9(10):e015602. Epub 2020 May 7.

Barbra Streisand Women's Heart Center Cedars-Sinai Smidt Heart Institute Los Angeles CA.

Background Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have evidence of diastolic dysfunction. Oxidative stress (OS) is associated with cardiovascular risk factors and adverse outcomes. The relationship between systemic OS and diastolic dysfunction is unknown. Methods and Results A subgroup of women (n=75) with suspected ischemia and no obstructive coronary artery disease who had both cardiac magnetic resonance imaging and OS measurements were enrolled in the WISE-CVD (Women Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction) study. Left ventricular end-diastolic pressure was measured invasively. Left ventricular end-diastolic volume and peak filling rate were assessed using cardiac magnetic resonance imaging. Aminothiol levels of plasma cystine and glutathione were measured as markers of OS. Spearman correlation and linear regression analyses were conducted. The group mean age was 54±11 years, and 61% had a resting left ventricular end-diastolic pressure >12 mm Hg. Cystine levels correlated negatively with the peak filling rate (=-0.31, =0.007) and positively with left ventricular end-diastolic pressure (=0.25; =0.038), indicating that increased OS was associated with diastolic dysfunction. After multivariate adjustment including multiple known risk factors for diastolic dysfunction and cardiovascular medications, cystine levels continued to be associated with peak filling rate (β=-0.27, =0.049) and left ventricular end-diastolic pressure (β=0.25; =0.035). Glutathione levels were not associated with indices of diastolic function. Conclusions OS, measured by elevated levels of cystine, is associated with diastolic dysfunction in women with evidence of ischemia and no obstructive coronary artery disease, indicating the role of OS in patients with ischemia and no obstructive coronary artery disease. Its role in the progression of heart failure with preserved ejection fraction should be explored further.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.015602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660868PMC
May 2020

Neural responses during acute mental stress are associated with angina pectoris.

J Psychosom Res 2020 07 11;134:110110. Epub 2020 Apr 11.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States of America; Department of Radiology, Emory University School of Medicine, United States of America; Atlanta VA Medical Center, Decatur, GA, United States of America.

Angina pectoris is associated with increased risk of adverse cardiovascular events in coronary artery disease (CAD) patients, an effect not entirely attributable to the severity of CAD.

Objective: Examine brain correlates of mental stress in patients with CAD with and without a history of angina.

Methods: Participants (n = 170) with stable CAD completed the Seattle Angina Questionnaire along with other psychometric assessments. In this cross-sectional study, participants underwent laboratory-based mental stress testing using mental arithmetic and public speaking tasks along with control conditions in conjunction with positron emission tomography brain imaging using radiolabeled water. Brain activity during mental stress was compared between participants who did or did not report chest pain/angina in the previous month. A factor analysis was coupled with dominance analysis to identify brain regions associated with angina.

Results: Participants reporting angina in the past month experienced greater (p < .005) activations within the left: frontal lobe (z = 4.01), temporal gyrus (z = 3.32), parahippocampal gyrus (z = 3.16), precentral gyrus (z = 3.14), right fusiform gyrus (z = 3.07), and bilateral cerebellum (z = 3.50) and deactivations within the right frontal gyrus (z = 3.67), left precuneus (z = 3.19), and left superior temporal gyrus (z = 3.11) during mental stress. A factor containing the left motor areas, inferior frontal lobe, and operculum (average McFadden's number addition = 0.057) in addition to depression severity (0.10) and adulthood trauma exposure (0.064) correlated with angina history.

Conclusions: Self-reported angina in patients with stable CAD is associated with increased neural responses to stress in a network including the inferior frontal lobe, motor areas, and operculum, potentially indicating an upregulated pain perception response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychores.2020.110110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082434PMC
July 2020
-->