scholarly journals Independent Effects of Kidney Function and Cholesterol Efflux on Cardiovascular Mortality

2021 ◽  
Author(s):  
Andreas Ritsch ◽  
Monika Hunjadi ◽  
Tatjana Stojakovic ◽  
Stephen Zewinger ◽  
Thimoteus Speer ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Function ◽  
Cardiovascular Mortality ◽  
Impaired Renal Function ◽  
Cholesterol Efflux ◽  
Strong Association ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function

Abstract BackgroundImpaired renal function is associated with cardiovascular and all-cause mortality. In the general population, HDL-cholesterol is associated with cardiovascular events, which is not true in patients with chronic kidney disease (CKD). This has been attributed to abnormal HDL function in CKD.MethodsIn this study, we analyzed the association between kidney function, cholesterol efflux capacity as one of the major HDL functions and cardiovascular mortality in 2469 patients of the Ludwigshafen Risk and Cardiovascular Health Study who all underwent coronary angiography.ResultsWe found a strong association between cholesterol efflux capacity and kidney function. Additionally, a genetic score of 53 SNPs associated with GRF and the uromodulin SNP rs12917707 was correlated inversely with cholesterol efflux. However, adjustment for eGFR and uromodulin as markers of kidney function did not affect the relationship between cholesterol efflux and cardiovascular mortality.ConclusionsWe suggest that impaired renal function lowers cholesterol efflux, but that this is not mediating the effects of impaired kidney function on cardiovascular mortality. Other mechanisms of low cellular cholesterol efflux may causally be involved in adverse cardiovascular outcomes.Trial registrationThe study was approved by the Ethics Committee at the “Aerztekammer Rheinland-Pfalz” and was performed conform to the declaration of Helsinki (837.255.97 [1394], approved January 8th, 1999).

scholarly journals Longitudinal Measures of Trimethylamine N-oxide and Incident Atherosclerotic Cardiovascular Disease Events in Older Adults: The Cardiovascular Health Study

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1434-1434
Author(s):  
Yujin Lee ◽  
Zeneng Wang ◽  
Heidi Lai ◽  
Marcia de Oliveira Otto ◽  
Rozenn Lemaitre ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Older Adults ◽  
Renal Function ◽  
Cystatin C ◽  
Impaired Renal Function ◽  
Cardiovascular Health ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Atherosclerotic Cardiovascular Disease ◽  
Community Based

Abstract Objectives Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite of dietary choline, L-carnitine and phosphatidylcholine-rich animal foods. Based on experimental studies and cohorts with prevalent disease, elevated TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction and elevated cystatin-C. Yet, the associations of serial TMAO levels with incident ASCVD in a community-based prospective cohort, and the potential mediating and modifying role of renal function, are not established. Methods We investigated the associations of serial measures of plasma TMAO, assessed at baseline and 7 years post baseline, with incident ASCVD among 4144 older adults in the Cardiovascular Health Study (CHS). TMAO was measured using stable isotope dilution LC/MS/MS (lab CV <6%). Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, sudden cardiac death, or other atherosclerotic death) was centrally adjudicated using medical records. Risk was assessed by multivariable Cox proportional hazards regression including time-varying demographics, lifestyle factors, medical history, and laboratory and dietary variables. We assessed potential mediating effects and interaction by renal function estimated by cystatin-C. Results During a median 15 years follow-up, 1757 ASCVD events occurred. After multivariable adjustment, TMAO was associated with a higher risk of ASCVD, with an extreme quintile HR (95% CI) of 1.22 (1.04, 1.44), P-trend = 0.01. This relationship appeared further mediated or confounded by estimated glomerular filtration rate (eGFR): adjusting for cystatin-C-based eGFR, the HR (95% CI) was 1.06 (0.98–1.25). Significant interaction was also observed by renal function (P-interaction < 0.001), with TMAO associated with higher risk of ASCVD among individuals with impaired renal function (eGFR ≤ 60) [1.63 (1.03–2.59)], but not normal baseline renal function (eGFR > 60) [1.15 (0.96–1.37)], even with further adjustment for continuous eGFR. Conclusions In this large community-based cohort of older US adults, higher serial measures of TMAO were associated with an elevated risk of ASCVD, in particular among those with impaired renal function. Funding Sources NIH, NHLBI.

scholarly journals Impaired Renal Function on Cholesterol Efflux Capacity, HDL Particle Number, and Cardiovascular Events

2018 ◽  
Vol 72 (6) ◽  
pp. 698-700 ◽  
Author(s):  
Shahzad Chindhy ◽  
Parag Joshi ◽  
Amit Khera ◽  
Colby R. Ayers ◽  
S. Susan Hedayati ◽  
...  
Keyword(s):  
Renal Function ◽  
Cardiovascular Events ◽  
Impaired Renal Function ◽  
Cholesterol Efflux ◽  
Particle Number ◽  
Cholesterol Efflux Capacity

scholarly journals Cholesterol Efflux Capacity Associates with the Ankle-Brachial Index but Not All-Cause Mortality in Patients with Peripheral Artery Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1407
Author(s):  
Robert K. Clemens ◽  
Monika Hunjadi ◽  
Andreas Ritsch ◽  
Lucia Rohrer ◽  
Thomas O. Meier ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cholesterol Efflux ◽  
Ankle Brachial Index ◽  
Mortality Rates ◽  
High Density Lipoproteins ◽  
Peripheral Artery ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
All Cause Mortality ◽  
Artery Disease

Background: Cholesterol efflux is an important mechanism by which high-density lipoproteins (HDLs) protect against cardiovascular disease. As peripheral artery disease (PAD) is associated with high mortality rates, mainly due to cardiovascular causes, we investigated whether cholesterol efflux capacity (CEC) of apolipoprotein B (apoB)-depleted plasma, a widely used surrogate of HDL function, may serve as a predictive marker for mortality in this patient population. Methods: In this prospective single-center study (median follow-up time: 9.3 years), apoB-containing lipoproteins were precipitated from plasma of 95 patients with PAD and incubated with J744-macrophages, which were loaded with radiolabeled cholesterol. CEC was defined as the fractional radiolabel released during 4 h of incubation. Results: Baseline CEC was lower in PAD patients that currently smoked (p = 0.015) and had a history of myocardial infarction (p = 0.011). Moreover, CEC showed a significant correlation with HDL-cholesterol (p = 0.003) and apolipoprotein A-I levels (p = 0.001) as well as the ankle-brachial index (ABI, p = 0.018). However, CEC did not differ between survivors and non-survivors. Neither revealed Kaplan–Meier and Cox regression analyses any significant association of CEC with all-cause mortality rates. Conclusion: Taken together, CEC is associated with ABI but does not predict all-cause mortality in patients with PAD.

HDL cholesterol efflux capacity and cardiovascular mortality

2015 ◽  
Vol 241 (1) ◽  
pp. e28
Author(s):  
A. Ritsch ◽  
A. Duerr ◽  
P. Kahler ◽  
T. Stojakovic ◽  
G. Silbernagel ◽  
...  
Keyword(s):  
Cardiovascular Mortality ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Cholesterol Efflux Capacity

Abstract 5011: Role of Autonomic Nervous System Dysregulation and Inflammation in the Increased Risk of Depression for Cardiovascular Mortality: The Cardiovascular Health Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Willem J Kop ◽  
Phyllis K Stein ◽  
Joshua I Barzilay ◽  
Russell P Tracy ◽  
John S Gottdiener
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Cardiovascular Mortality ◽  
Inflammatory Markers ◽  
Cardiovascular Health ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Scaling Exponent ◽  
Autonomic Nervous

The increased cardiovascular (CV) risk associated with depression is hypothesized to be explained by autonomic nervous system (ANS) dysregulation and inflammatory processes. This study determines the role of ANS dysregulation and inflammation in the predictive value of depression for CV mortality. 908 participants of the Cardiovascular Health Study (age 71±5 yrs) free of CV disease were evaluated for depression (CES-D scale), ANS dysregulation by abnormal non-linear heart rate variability (decreased short-term fractal scaling exponent), and inflammation (IL-6, CRP, fibrinogen and WBC). Predictors of CV mortality were examined using Cox regression analysis, adjusting for age, sex, race, systolic blood pressure, diabetes, subclinical disease, use of beta-blockers, smoking status, BMI, and physical activity (median follow-up=13.3 yrs). Risks were calculated for subgroups based on the presence or absence of depression, and ANS or inflammatory CV risk factors (Figure ). Depression was predictive of CV mortality (RR=1.88, CI=1.23–2.86), ANS dysregulation (p=0.014) and inflammatory markers (IL-6 p=0.072; WBC p=0.033; and fibrinogen p=0.050) were correlated with depression. The association of depression with CV mortality occurred primarily in the presence of ANS dysregulation and/or inflammation (Figure ). Addition of ANS and inflammatory markers to the multivariate model did not substantially reduce the CV mortality risk of depression (adjusted RR=1.65, CI=1.03–2.65). Depression is predictive of cardiovascular mortality, and the elevated risk is additive to autonomic nervous system dysregulation and inflammation

scholarly journals Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: The Cardiovascular Health Study

2019 ◽  
Vol 74 (4) ◽  
pp. 501-509 ◽  
Author(s):  
Dominik Steubl ◽  
Petra Buzkova ◽  
Pranav S. Garimella ◽  
Joachim H. Ix ◽  
Prasad Devarajan ◽  
...  
Keyword(s):  
Kidney Function ◽  
Cardiovascular Health ◽  
The Elderly ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Kidney Function Decline

P3767Progressive left atrial remodeling associates with cholesterol efflux capacity of HDL in atrial fibrillation patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Takano ◽  
H Iwata ◽  
K Miyosawa ◽  
T Funamizu ◽  
H Hayashi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Left Atrial ◽  
Cholesterol Efflux ◽  
Control Group ◽  
Atrial Remodeling ◽  
Inverse Association ◽  
Structural Remodeling ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function

Abstract Background The clinical significance of high-density lipoprotein (HDL) function, represented by cholesterol efflux capacity (CEC), in addition to serum HDL cholesterol (HDL-C) levels, has been recognized in the pathogenesis and prognosis in patients with atherosclerotic cardiovascular diseases. However, the roles of HDL in the development and the progression of atrial fibrillation (AF), has been rarely evaluated. In this study, we thus hypothesized that the compromised HDL function may be associated with the progression of pathological structural remodeling in left atrium (LA). Objective We explored the association between CEC of HDL and the left atrial dimension (LAD), a maker of structural remodeling in the LA, in patients with AF and control. Methods This is a single center case-control study including consecutive 260 AF patients (AF group) and 34 paroxysmal supraventricular tachycardia (PSVT) patients (PSVT group, served as a control group), who underwent catheter ablation from July 2017 to December 2018. Blood samples were collected before catheter ablation procedure. CEC of HDL was measured by using ex vivo radiotracer system that involved incubation of [3H] cholesterol-loaded J774.1 murine macrophage-like cells with apoB-depleted serum. Results Serum HDL-C level was lower in AF group compared to those of PSVT group (55.3±15.3mg/dl vs 61.7±13.3mg/dl: p=0.024). As a marker of HDL function, CEC of HDL was significantly lower in patients with AF group compared to those in PSVT patients (4.74±0.84% vs 5.20±0.99%: p=0.005, Fig 1). In all patients including both groups, CEC of HDL was inversely correlated with LAD (r=−0.25; p<0.001, Fig 2), indicating the inverse association between HDL function and the progression of structural remodeling in AF. Moreover, multivariate logistic regression analysis adjusted by age, gender, body mass index, ejection fraction, and HDL-C demonstrated that increase in CEC of HDL was associated with the lower risk to be highest quartiles of LAD (>42mm), even adjusted by serum HDL-C levels (odds ratio of 1-SD elevation in CEC of HDL for LAD>42mm: 0.63; 95% confidence interval: 0.40–0.97, p=0.037), which implicated the link between HDL function and progression of left atrial structural remodeling. Conclusion Findings in this study may suggest that compromised HDL functionality is associated with the pathogenesis of left atrial structural remodeling in AF patients.

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