Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double‐blind randomized study

Solberg, Ole Geir; Stavem, Knut; Ragnarsson, Àsgrìmur; Beitnes, Jan Otto; Skårdal, Rita; Seljeflot, Ingebjørg; Ueland, Thor; Aukrust, Pål; Gullestad, Lars; Aaberge, Lars

doi:10.1002/ccd.28157

Cited by 13 publications

(10 citation statements)

References 42 publications

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“…One hundred fifty‐five articles received a complete review, and 56 studies met inclusion criteria and were included in the meta‐analysis (Figure 2 ). 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , …”

Section: Resultsmentioning

confidence: 99%

Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta‐Analysis

Mileva

Nagumo

Mizukami

et al. 2022

JAHA

102

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Background A relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary arteries. However, the prevalence of coronary microvascular disease (CMD) and coronary spasm in patients with nonobstructive coronary artery disease remains to be determined. The objective of this study was to determine the prevalence of coronary CMD and coronary vasospastic angina in patients with no obstructive coronary artery disease. Methods and Results A systematic review and meta‐analysis of studies assessing the prevalence of CMD and vasospastic angina in patients with no obstructive coronary artery disease was performed. Random‐effects models were used to determine the prevalence of these 2 disease entities. Fifty‐six studies comprising 14 427 patients were included. The pooled prevalence of CMD was 0.41 (95% CI, 0.36–0.47), epicardial vasospasm 0.40 (95% CI, 0.34–0.46) and microvascular spasm 24% (95% CI, 0.21–0.28). The prevalence of combined CMD and vasospastic angina was 0.23 (95% CI, 0.17–0.31). Female patients had a higher risk of presenting with CMD compared with male patients (risk ratio, 1.45 [95% CI, 1.11–1.90]). CMD prevalence was similar when assessed using noninvasive or invasive diagnostic methods. Conclusions In patients with no obstructive coronary artery disease, approximately half of the cases were reported to have CMD and/or coronary spasm. CMD was more prevalent among female patients. Greater awareness among physicians of ischemia with no obstructive coronary arteries is urgently needed for accurate diagnosis and patient‐tailored management.

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Section: Resultsmentioning

confidence: 99%

Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta‐Analysis

Mileva

Nagumo

Mizukami

et al. 2022

JAHA

102

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“…Trial design and participants. Participants were recruited, and the study was performed as previously described 17 . In short; study participants were recruited at Oslo University Hospital Rikshospitalet, a tertiary care center in Oslo, Norway between June 2012 and December 2015.…”

Section: Methodsmentioning

confidence: 99%

“…Demographic data, medical history and medication were collected at baseline as previously described 17 . Additional dietary data were collected using a questionnaire, as previously described 18 , and participants were instructed not to change diet during the study course.…”

Section: Sample Collectionmentioning

confidence: 99%

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Rosuvastatin alters the genetic composition of the human gut microbiome

Kummen

Solberg

Storm-Larsen

et al. 2020

Sci Rep

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The gut microbiome contributes to the variation of blood lipid levels, and secondary bile acids are associated with the effect of statins. Yet, our knowledge of how statins, one of our most common drug groups, affect the human microbiome is scarce. We aimed to characterize the effect of rosuvastatin on gut microbiome composition and inferred genetic content in stool samples from a randomized controlled trial (n = 66). No taxa were significantly altered by rosuvastatin during the study. However, rosuvastatin-treated participants showed a reduction in the collective genetic potential to transport and metabolize precursors of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO, p < 0.01), and an increase of related metabolites betaine and γ-butyrobetaine in plasma (p < 0.01). Exploratory analyses in the rosuvastatin group showed that participants with the least favorable treatment response (defined as < median change in high-density/low-density lipoprotein (HDL/ LDL) ratio) showed a marked increase in TMAO-levels compared to those with a more favorable response (p < 0.05). Our data suggest that while rosuvastatin has a limited effect on gut microbiome composition, it could exert broader collective effects on the microbiome relevant to their function, providing a rationale for further studies of the influence of statins on the gut microbiome. Originally discovered for their anti-microbial properties 1 , statins primarily reduce cholesterol levels and are first-line agents in the management of coronary artery disease (CAD) 2. The use of statins has been increasing rapidly in recent decades, and they are now one of the most commonly prescribed group of drugs in Western countries 2,3. The primary mode of action is inhibition of hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the liver leading to decreased levels of low-density lipoprotein (LDL) cholesterol, but statins have other potential beneficial effects e.g., anti-inflammatory properties, inhibition of matrix metalloproteinases (MMPs) leading to plaque stabilization and inhibition of platelet aggregation 4. The mechanisms underlying these pleiotropic effects are not completely understood and may not necessarily be mediated through HMG-CoA reductase inhibition 5-7. Changes in the composition and function of gut microbiome have been implicated in the pathogenesis of a wide range of human conditions including various systemic disorders like cardiometabolic and autoimmune disorders 8,9. In cardiovascular disease (CVD), the gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) and related metabolites, has been associated cardiovascular risk 8,9. The large intra-individual variation

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“…In a randomized, placebo-controlled study comprising 24 weeks of treatment with angiotensin converting enzyme inhibitor to normotensive participants, there was no effect on CFVR [42]. In a recent intervention study of patients with newly diagnosed myocardial infarction, six months' treatment with rosuvastatin had no effect on invasively assessed coronary microvascular function [43]. Thus, trials showing effect of intervention on non-endothelial dependent coronary vascular function are lacking.…”

Section: Coronary Microvascular Dysfunctionmentioning

confidence: 98%

Comprehensive treatment of microvascular angina in overweight women – a randomized controlled pilot trial

Bové¹,

Nilsson²,

Pedersen³

et al. 2020

PLoS ONE

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Aims Coronary microvascular dysfunction (CMD) carries a poor cardiovascular prognosis and may explain angina in women without obstructive coronary artery disease (CAD). Currently, no evidence-based treatment for CMD exists. We investigated whether reducing cardiovascular risk factors improves symptoms and microvascular function in women with non-endothelial dependent CMD and no obstructive CAD. Methods We randomized 62 women aged 40–75, with body mass index (BMI) >25 kg/m2, angina ≥monthly, and coronary flow velocity reserve (CFVR) ≤2.5 to a 24-week intervention comprising low energy diet, exercise training, and optimized treatment of hypertension, dyslipidemia and diabetes or to control. Patients were assessed before randomization and after 24 weeks. Primary outcomes were CFVR assessed by transthoracic Doppler stress-echocardiography and angina burden by Seattle Angina Questionnaire (SAQ). Secondary outcomes were exercise capacity, body composition, glycemic control, myocardial function, and anxiety and depression symptoms. Results Fifty-six participants (90%) completed the study. Median (IQR) age was 65.2 (57.1;70.7) years, BMI was 30.1 (28.4;32.7) kg/m2. The intervention resulted in relevant improvement in angina symptoms (9-21-point increase on SAQ-scales (all p<0.01)) but had no effect on CFVR (p = 0.468). Mean (CI) weight loss was 9.6 (7.80;11.48) kg, (p<0.0001). There was a significant mean (CI) decrease in depression symptoms = 1.16 (0.22;2.12), triglycerides = 0.52 (0.25;0.78) mmol/L, total cholesterol = 0.55 (0.12;0.98) mmol/L, and HbA1c in diabetics = 27.1 (1.60;52.6) mmol/mol but no effect on other secondary outcomes. Conclusion A major weight loss and intensified risk factor control resulted in significantly improved angina burden but no improvement of coronary microvascular function among women with microvascular angina.

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Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double‐blind randomized study

Cited by 13 publications

References 42 publications

Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta‐Analysis

Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta‐Analysis

Rosuvastatin alters the genetic composition of the human gut microbiome

Comprehensive treatment of microvascular angina in overweight women – a randomized controlled pilot trial

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