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- Blomster, Juuso I., et al.
(author)
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Coronary flow reserve as a link between exercise capacity, cardiac systolic and diastolic function
- 2016
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 217, s. 161-166
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Journal article (peer-reviewed)abstract
- Background: Decreased coronary flow reserve (CFR) is associated with increased risk of adverse cardiovascular events. We sought to investigate how CFR from left anterior descending (LAD) coronary artery reflects clinical markers of cardiac function. Methods: We enrolled 400 patients referred for myocardium perfusion scintigraphy due to chest pain at Sahlgrenska University Hospital in Gothenburg, Sweden. Transthoracic echocardiography including adenosine-assisted CFR in LAD was performed at a separate occasion. Results: Median age was 62 years (range 32-83) and 47% were female. Prior myocardial infarction had occurred in 28% of the population. In adjusted multivariate models, CFR in LAD was associated with echocardiography left ventricle ejection fraction at rest (beta = 0.97, p = 0.033) as well as under stress (beta = 1.52, p = 0.0056) and maximum exercise capacity (beta = 6.27, p = 0.026). CFR in LAD outweighed left ventricle ejection fraction as the determinant of maximum exercise capacity. Hyperaemic diastolic mitral annulus peak velocity measured by vector velocity imaging was inversely associated with LAD CFR (beta = -0.39, p = 0.0077). In subgroup analyses these findings were associated with normal coronary perfusion in myocardium perfusion scintigraphy. Conclusions: In patients with angina-like symptoms CFR measured in LAD reflects well both systolic and diastolic cardiac function emphasizing the essential role of myocardial microvascular circulation in cardiac physiology. (C) 2016 Published by Elsevier Ireland Ltd.
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| 2. |
- Utkovic Westergren, Helena, et al.
(author)
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Determinants of coronary flow reserve in non-diabetic patients with chest pain without myocardial perfusion defects
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Journal article (peer-reviewed)abstract
- Background Microvascular dysfunction could be responsible for chest pain in patients without myocardial perfusion defects. We evaluated microvascular function using ultrasound-assessed coronary flow reserve (CFR) in patients with chest pain and normal myocardial perfusion scintigram. Secondly, we investigated association between cardiovascular parameters and decreased CFR in a sex specific manner. A total of 202 (128 women) non-diabetic patients with chest pain and suspected myocardial ischemia, but without myocardial perfusion defects on myocardial perfusion scintigram, were enrolled and underwent CFR examination and blood sampling. All patients were followed- up for cardiovascular events. We used a supervised principal component analysis including 66 variables such as clinical parameters, ongoing medication, coronary artery disease history, lipids, metabolic parameters, inflammatory and other cardiovascular parameters. During a median follow-up time of 5.4 years, 25 cardiovascular events occurred; (men; 18, women; 7). Average CFR of the study cohort was 2.7 +/- 1.2 and 14% showed impaired CFR< 2.0. In an adjusted Cox regression analysis, CFR< 2.0 independently predicted eventfree survival (HR: 2.5, p = 0.033). In the supervised principal component analysis high insulin resistance assessed by Homeostatic model assessment for insulin resistance was the strongest biochemical marker associated with decreased CFR. Interestingly, upon sex specific multivariable linear regression analysis, the association was only significant in men (beta = -0.132, p = 0.041) while systolic blood pressure remained an independent predictor in women (beta = -0.009, p = 0.011). In non-diabetic patients with chest pain without myocardial perfusion defects, low CFR has prognostic value for future cardiovascular events. Insulin resistance appears to be a marker for decreased CFR in men. Indeed, in the context of contribution of traditional risk factors in this patient population, the value of systolic blood pressure seems to be important in the women.
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| 3. |
- Utkovic Westergren, Helena
(author)
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Insulin resistance and cardiovascular function - Observational, translational and interventional studies
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Background: Microvascular disease is now recognized as an important driver for cardiovascular mortality and morbidity. Diabetic patients are known to suffer from this condition, leading to e.g. coronary ischemia as well as kidney dysfunction. Accumulating evidences indicate that the vascular pathological alterations may be a direct consequence of impaired glucose homeostasis and may occur long before diabetes is diagnosed. Early risk identification and a better understanding of associated mechanisms could be of great importance in disease management. Thus, the overall hypothesis of this thesis was that impaired glucose homeostasis already in the non-diabetic stage is associated with coronary and peripheral microvascular dysfunction and an unfavorable systemic risk profile, possibly facilitating progression of cardiovascular disease. For translational understanding, we hypothesized that obese insulin resistant leptin-deficient (ob/ob) mice could be a potential model for microvascular dysfunction and associated mechanisms. Finally, we hypothesized that short-term personalized lifestyle intervention may improve coronary microcirculation in healthy subjects. Summary of results: My thesis shows that high insulin resistance assessed by the Homeostatic model assessment for insulin resistance (HOMA-IR) added independent prognostic value in patients with chest pain without myocardial perfusion defects. HOMA-IR was inversely associated with decreased peripheral vascular function, increased systemic pro-inflammatory state and decreased levels of pro-angiogenic vascular growth factors (Paper I). Also, impaired coronary flow reserve (CFR) predicted cardiovascular outcome in these patients and HOMA-IR was the strongest biochemical marker associated with decreased CFR. Interestingly, upon gender specific analysis, HOMA-IR seemed to be the strongest predictor of decreased CFR in men while systolic blood pressure was the strongest predictor in women (Paper II). Furthermore, impaired CFR and increased renal vascular resistance were observed in the ob/ob mice compared to lean controls. Possible mechanisms behind these observations were an impaired nitric oxide pathway as well as decreased renal vascular density (Paper III). Finally, CFR was improved with a personalized and supervised exercise and diet program in healthy volunteers (Paper IV). Conclusions: This thesis suggests that insulin resistance measured by HOMA-IR confers independent prognostic information in non-diabetic patients with chest pain without myocardial perfusion defects. Furthermore, increased HOMA-IR is associated with poor cardiovascular status and there seems to be gender specific mechanisms associated with coronary microvascular dysfunction. In addition, the ob/ob mice may be a useful translational model for interventional studies to improve understanding of microvascular complications in impaired glucose homeostasis. Finally, three months of personalized life style intervention can enhance cardiovascular function in healthy subjects.
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| 4. |
- Utkovic Westergren, Helena, et al.
(author)
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Randomized clinical trial studying effects of a personalized supervised lifestyle intervention program on cardiovascular status in physically inactive healthy volunteers.
- 2018
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:10, s. 9498-9511
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Journal article (peer-reviewed)abstract
- The impact of personalized exercise training and a healthy dietary lifestyle in healthy volunteers on coronary flow reserve and cardiovascular function remains to be investigated in a controlled study setting.To examine the effects of a Mediterranean-inspired diet combined with regular physical exercise (standard) and a personalized supervised exercise program (DAPS) on coronary flow reserve and cardiovascular function.The number of males were 10 (59%) and 9 (47%) and mean age was 54 ± 12 and 55 ± 5 years in standard versus DAPS group, respectively. Primary outcomes were in addition to improved body composition and aerobic capacity, increased TDE-CFR (5.0%, CI:1.62,8.64, p = 0.005) and left ventricle ejection fraction (LVEF) during hyperemia (10.2%, CI:1.62,19.4, p = 0.022) in DAPS adjusted for the control period. Also, plasma fibrinogen decreased (-12.1%, CI:-22.0,-0.92, p = 0.035) in the DAPS group. Secondary outcomes, after adjusting DAPS intervention effects for the standard-training period, TDE-CFR and hyperemic LVEF remained significantly improved.This randomized, controlled clinical trial (URL: http://www.clinicaltrials.gov NCT02713724) included 36 healthy volunteers who underwent exercise ECG before randomization to standard or DAPS groups. Standard-group was given gym-membership with limited instructions and general dietary advice. DAPS-group received personalized supervised exercise programs and more detailed dietary advice with regular contact with a personal trainer. Effects were evaluated after 3 months. All participants underwent coronary flow reserve by transthoracic ultrasound (TDE-CFR), blood marker analysis and examinations of vascular function. Standard-group was evaluated pre-control, post-control (=pre-intervention) and post-intervention. DAPS-group was examined at pre-intervention and post-intervention.A personalized supervised training- and diet program improves cardiovascular status in healthy subjects with a physically inactive lifestyle and may be a promising approach for cardiovascular prevention in the general population.
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