Coronary microvascular function and visceral adiposity in patients with normal body weight and type 2 diabetes

Chowdhary, Amrit; Thirunavukarasu, Sharmaine; Jex, Nicholas; Coles, Lauren; Bowers, Charles W.; Sengupta, Anshuman; Swoboda, Peter; Witte, Klaus; Cubbon, Richard M; Xue, Hui; Kellman, Peter; Greenwood, John P; Plein, Sven; Levelt, Eylem

doi:10.1002/oby.23413

Cited by 8 publications

(13 citation statements)

References 46 publications

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“…Chowdary et al recently described that people with diabetes have greater visceral adiposity (including epicardial adiposity) than those without diabetes even when of normal weight. [15] Visceral adiposity is independently associated with higher 10-year cardiovascular disease risk. [38] It is notable that indices of adiposity were the strongest (albeit modest) correlates of abnormal cardiovascular phenotypes in people with and without DM in our analysis.…”

Section: Discussionmentioning

confidence: 99%

“…These support the notion that DM in the context of ‘normal’ BMI is still associated with important cardiovascular abnormalities. [14,15]…”

Section: Introductionmentioning

confidence: 99%

“…These support the notion that DM in the context of 'normal' BMI is still associated with important cardiovascular abnormalities. [14,15] The literature defining the complex relationship between DM, BMI and cardiovascular disease lacks data leveraging multimodality cardiovascular imaging and hard outcomes within a single cohort of sufficient size to study people with normal BMI and DM. To address this, we used the UK Biobank (UKB) cohort study.…”

Section: Introductionmentioning

confidence: 99%

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The relationship between diabetes, obesity and cardiovascular disease phenotypes: a UK Biobank cohort study

Brown

Drozd

McGowan

et al. 2023

Preprint

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Introduction Obesity and diabetes mellitus (DM) frequently co-exist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events and mortality in a large cohort stratified by body mass index (BMI) and DM. Methods 451,355 UK Biobank participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and DM status. We examined cardiovascular biomarkers including: carotid intima-media thickness (CIMT); arterial stiffness; left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRR) for myocardial infarction, ischaemic stroke and cardiovascular death, with normal weight non-DM as comparator. Results 5% of participants had DM (10% normal weight, 34% overweight and 55% obese; versus 34%, 43% and 23%, respectively, in non-DM). In the non-DM group, overweight/obesity was associated with higher CIMT, arterial stiffness and CCI, and lower LVEF (p<0.05); these relationships were diminished in the DM group. Within BMI classes, DM was associated with adverse cardiovascular phenotype (p<0.05), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischaemic stroke and cardiovascular mortality all rose across increasing BMI categories in the DM and non-DM groups (p<0.05). However, normal weight DM had higher cardiovascular mortality than obese non-DM (IRR 2.81 [95% confidence interval: 2.24-3.54] vs IRR 1.84 [1.70-1.98]). Conclusions Obesity and DM are additively associated with adverse cardiovascular biomarkers and mortality risk. Whilst adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting other factors underpin the high cardiovascular risk of normal-weight diabetes.

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Section: Discussionmentioning

confidence: 99%

“…These support the notion that DM in the context of ‘normal’ BMI is still associated with important cardiovascular abnormalities. [14,15]…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The relationship between diabetes, obesity and cardiovascular disease phenotypes: a UK Biobank cohort study

Brown

Drozd

McGowan

et al. 2023

Preprint

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“…Perfusion imaging used free-breathing, motion-corrected automated in-line perfusion mapping. Adenosine was infused at a rate of 140µg/kg/min, for a minimum of 3 minutes according to hemodynamic and symptomatic response as previously described 21 . Two trained cardiologists with advanced life support training monitored the patients during adenosine stress imaging, however adenosine stress was tolerated well by all patients during the stress perfusion studies.…”

Section: Methodsmentioning

confidence: 99%

“…Native T1 maps were acquired in 3 short-axis slices, using a breath-held modified look-locker inversion recovery acquisition as previously described 21 . Post-contrast T1 mapping was performed using the same approach 15 minutes after the last contrast injection.…”

Section: Cardiovascular Magnetic Resonancementioning

confidence: 99%

Cardiac remodeling in moderate aortic stenosis

Giannoudi,

Procter,

Kotha

et al. 2024

Preprint

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STRUCTURED ABSTRACTBackgroundAortic stenosis (AS) accounts for substantial global morbidity and premature mortality even in moderate AS (Mod-AS). The mechanisms for this adverse prognosis in Mod-AS, however, remain poorly understood, although the myocardial remodeling response is thought to be critical. We aimed to prospectively assess myocardial remodeling, perfusion and energetics differences in Mod-AS and severe AS (Severe-AS).MethodsFifty-two Severe-AS and 25 Mod-AS patients and 18 demographically-matched controls underwent cardiovascular magnetic resonance and phosphorus-magnetic resonance spectroscopy to define left ventricular (LV) mass and function, global longitudinal shortening (GLS), rest and adenosine-stress myocardial blood flow (MBF), myocardial perfusion reserve (MPR), layer-specific perfusion metrics (subendocardial [Endo], subepicardial [Epi] MBF and MPR, and Endo-to Epi-MBF ratio [Endo/Epi]), myocardial scar on late gadolinium enhancement (LGE) imaging, and myocardial energetics (phosphocreatine:ATP ratio [PCr/ATP]).ResultsCompared to controls, from Mod-AS to Severe-AS there was a progressive increase in LV concentricity (LV-mass/LV-end-diastolic-volume)(controls:0.58[0.54,0.62], Mod-AS:0.74[0.64,0.84], Severe-AS:0.89[0.83,0.95]g/mL;P<0.0001), LV mass-index (controls: 46[40,51], Mod-AS: 58[51,65], Severe-AS: 70[65,75]g/m2;P<0.0001) and stepwise decline in GLS (controls:19.9[17.6,22.2], Mod-AS:17.7[16.6,18.8], Severe-AS:13.4[12.5,14.4]%;P<0.0001) with significant differences between Mod-AS and Severe-AS for all three comparisons.Both stress MBF (controls:2.1[1.9,2.3], Mod-AS:1.9[1.6,2.2], Severe-AS:1.3[1.2,1.5]ml/min/g;P<0.0001) and MPR (controls:3.3[2.8,3.6], Mod-AS:2.8[2.4,3.2], Severe-AS:1.9[1.8,2.1];P<0.0001) were only significantly reduced in Severe-AS compared to controls, with significant differences also detected between Mod-AS and Severe-AS. However, stress-endo-MBF (controls:2.0[1.8,2.3], Mod-AS:1.7[1.5,2.0], Severe-AS:1.2[1.1,1.3] ml/min/g;P<0.0001), stress-Endo/Epi (controls:1.00[0.93,1.07], Mod-AS:0.87[0.80,0.94], Severe-AS:0.81[0.75,0.82];P<0.0001), rest-Endo/Epi (controls:1.12[1.10,1.14], Mod-AS:1.06[1.03,1.09], Severe-AS:1.03[1.02,1.06];P<0.0001) and endo-MPR (controls:3.2[2.7,3.6], Mod-AS:2.5[2.1,2.9], Severe-AS:1.7[1.5,1.8];P<0.0001) were all significantly reduced in both Mod-AS and Severe-AS.Compared to controls, both AS groups showed significantly lower PCr/ATP (controls:2.2[2.0,2.3], Mod-AS:1.8[1.6,2.0], Severe-AS:1.7[1.6,1.8];P<0.0001) and shorter 6-minute-walk-distance (controls:525[495,555], Mod-AS:420[375,465]m, Severe-AS:345[248,420]m;P<0.0001).Only the Severe-AS group had evidence of non-ischemic myocardial scarring on LGE (2.9[0.0,6.2]%), which was detected in 65% (n=34) of patients. Neither group had evidence of ischemic scar.The AS severity (peak aortic valve velocity) correlated with the stress-MBF (r=-0.45,P=0.0003), MPR (r=-0.44,P=0.0005) and GLS (r=-0.47,P=0.0001).ConclusionsModerate and severe AS are both associated with cardiac concentric hypertrophy, reductions in myocardial energetics, subendocardial hypoperfusion, and limitations in exercise distance. Patients with Severe-AS exhibit a more pronounced phenotype with worse LV hypertrophy, contractile dysfunction and myocardial scarring compared to patients with Mod-AS.CLINICAL PERSPECTIVESWhat is new:Patients with moderate aortic stenosis show cardiac concentric hypertrophy, reduction in myocardial energetics, shorter 6-minute walk distance compared to age-and sex-matched controls, but no evidence of myocardial scarring.Global myocardial perfusion metrics of rest and stress myocardial blood flow or myocardial perfusion reserve do not show significant reductions in patients with moderate aortic stenosis.The perfusion dynamics of the epicardial and endocardial layers differ in the presence of moderate aortic stenosis, with significant reductions in endocardial stress myocardial blood flow, rest and stress endocardial to epicardial myocardial blood flow ratio, and endocardial as well as epicardial myocardial perfusion reserve compared to controls.What Are the Clinical Implications?While milder compared to that seen in severe aortic stenosis, the degree of adverse myocardial remodeling and subendocardial hypoperfusion associated with moderate aortic stenosis may be clinically important for the cardiovascular clinical outcomes in patients with moderate aortic stenosis.Larger prospective serial studies and randomized trials are needed to better understand the mechanisms of high cardiovascular and all-cause mortality rates in patients with moderate aortic stenosis.

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Coronary microvascular function and visceral adiposity in patients with normal body weight and type 2 diabetes

Chowdhary

Thirunavukarasu

Jex

et al. 2022

Obesity

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Objective: This study sought to assess whether diabetes affects coronary microvascular function in individuals with normal body weight. Methods: Seventy-five participants (30 patients with type 2 diabetes [T2D] who were overweight [O-T2D], 15 patients with T2D who were lean [LnT2D], 15 healthy volunteers who were lean [LnHV], and 15 healthy volunteers who were overweight [O-HV]) without established cardiovascular disease were recruited. Participants underwent magnetic resonance imaging for assessment of subcutaneous, epicardial, and visceral adipose tissue areas, adenosine stress myocardial blood flow (MBF), and cardiac structure and function. Results: Stress MBF was reduced only in the O-T2D group (mean [SD], LnHV = 2.07 [0.47] mL/g/min, O-HV = 2.08 [0.42] mL/g/min, LnT2D = 2.16 [0.36] mL/g/min, O-T2D = 1.60 [0.28] mL/g/min; p ≤ 0.0001). Accumulation of visceral fat was evident in the LnT2D group at similar levels to the O-HV group (LnHV = 127 [53] cm 2 , O-HV = 181 [60] cm 2 , LnT2D = 182 [99] cm 2 , O-T2D = 288 [72] cm 2 ; p < 0.0001). Only the O-

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Coronary microvascular function and visceral adiposity in patients with normal body weight and type 2 diabetes

Cited by 8 publications

References 46 publications

The relationship between diabetes, obesity and cardiovascular disease phenotypes: a UK Biobank cohort study

The relationship between diabetes, obesity and cardiovascular disease phenotypes: a UK Biobank cohort study

Cardiac remodeling in moderate aortic stenosis

Coronary microvascular function and visceral adiposity in patients with normal body weight and type 2 diabetes

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