Predicting Heart Failure Events in Patients with Coronary Heart Disease and Impaired Glucose Tolerance: Insights from the Acarbose Cardiovascular Evaluation (ACE) Trial

2020 ◽  
Author(s):  
Malgorzata Wamil ◽  
John J. V. McMurray ◽  
Charles A.B. Scott ◽  
Ruth L. Coleman ◽  
Yihong Sun ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Plasma Creatinine ◽  
Cardiovascular Evaluation

Abstract BACKGROUND Heart failure is a fatal complication of type 2 diabetes but little is known about its incidence in patients with impaired glucose tolerance (IGT). We used Acarbose Cardiovascular Evaluation (ACE) trial data to identify predictors of hospitalisation for heart failure (hHF) or cardiovascular (CV) death in patients with coronary heart disease (CHD) and IGT randomized to acarbose 50mg TID or placebo. METHODS Independent hHF or hHF/CV death risk factors were determined using Cox proportional hazards models, with participants censored at first hHF event, CV death, or end of follow-up. Baseline variables evaluated included age, sex, body mass index, smoking, plasma creatinine, prior CV events, fasting and 2-hour post-load glucose, and HbA1c. Those with nominal univariate associations (P<0.1) were entered into a multivariate model, with P<0.05 required for retention. Recurrent hHF events were analysed using the Andersen-Gill model, a generalisation of the Cox proportional hazards model, and logistic regression was used for death following hHF. RESULTS During median 5 years follow-up, hHF/CV death occurred in 393 (6.0%) ACE participants (triggered by 138 hHF events and 255 CV deaths). Significant hHF/CV death multivariate predictors were higher age and plasma creatinine, as well as prior heart failure (HF), myocardial infarction (MI), atrial fibrillation (AF) and stroke. Acarbose, compared with placebo, did not reduce hHF/CV death (hazard ratio [HR] 0.89, 95% CI 0.64–1.24, P=0.48) or hHF (HR 0.90, 95% CI 0.74–1.10, P=0.32). Forty of the 138 participants who experienced hHF had ³2 admissions, and 58 died. No significant effect of acarbose, compared with placebo, was seen for recurrent hHF (HR 1.19, 95% CI 0.92-1.55, p=0.19), or for all-cause mortality (odds ratio 1.49, 95% CI 0.75-2.95, p=0.25).CONCLUSIONS Patients with CHD and IGT at greater risk of hHF/CV death were older with higher plasma creatinine, and had prior HF, MI, AF or stroke. Addition of acarbose to optimized CV therapy did not reduce the risk of hHF/CV death or hHF. Clinical Trial Registration: ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513.

Abstract P323: Pulse Pressure and Incident Acute Coronary Heart Disease Events in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Stephen P Glasser ◽  
Daniel L Halberg ◽  
Charles Sands ◽  
Paul Muntner ◽  
Monika Safford
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Racial Differences ◽  
Pulse Pressure ◽  
Proportional Hazards ◽  
Linear Trend ◽  
Cox Proportional Hazards ◽  
Cvd Risk

Background: Increased attention has been given to pulse pressure (PP) as a potential independent risk factor of cardiovascular disease. We examined the relationship between PP and incident acute coronary heart disease (CHD). Methods: We used data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study of 30,239 black and white participants aged 45 years or older and enrolled between 2003 and 2007. Baseline data included a 45-minute interview and in-home visit during which blood pressure was assessed and recorded as the average of two measurements obtained after a 5 minute seated rest. PP (SBP-DBP) was classified into 4 groups (<45, 45-54, 54.1-64, >64.1 mmHg). Telephone follow-up occurred every six months for self or proxy-reported suspected events, triggering medical record retrieval and adjudication by experts. Cox-proportional hazards models examined the association of incident CHD with PP groups, adjusting for socio-demographic and clinical risk factors. Results: This analysis included 22,909 participants free of CHD at baseline, with mean age 64.7±9.4 years; 40.4%were black, 44.6% were male and they experienced a total of 515 incident CHD events over a mean 3.4 yrs of follow-up (maximum 6 years). In unadjusted analyses, compared with PP<45 mmHg, each higher PP group had incrementally higher hazard ratios (HR) for incident CHD (HR 1.28 {95% CI 1.02-1.60}, 2.05 {1.63-2.56}, 3.82 {3.08-4.74}, p<0.001 for linear trend). This relationship persisted after fully adjusting including SBP for the highest PP group (HR 0.96 {0.75-1.21}, 1.12 {0.86-1.46}, 1.51 {1.09-2.10}, p trend <0.0001). Conclusions: High PP was associated with incident CHD, even when accounting for SBP and numerous other CVD risk factors.

scholarly journals Impact of Acarbose on Incident Diabetes and Regression to Normoglycemia in People with Coronary Heart Disease and Impaired Glucose Tolerance: Insights from the ACE Trial

2020 ◽  
Author(s):  
Hertzel C. Gerstein ◽  
Ruth L. Coleman ◽  
Charles A.B. Scott ◽  
Shishi Xu ◽  
Jaakko Tuomilehto ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Multiple Testing ◽  
Angiotensin Receptor Blockers ◽  
Incident Diabetes ◽  
Channel Blockers ◽  
Cardiovascular Evaluation ◽  
The Impact

OBJECTIVE <p>We examined the impact of acarbose, an alpha-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD).</p> <p>RESEARCH DESIGN AND METHODS</p> <p>Participants were randomly assigned to acarbose or placebo and followed with four-monthly FPGs and annual OGTTs. Incident diabetes was defined as two successive diagnostic FPGs ≥ 7 mmol/L or 2-hr PGs ≥ 11.1 mmol /L while taking study medication, or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG <6.1 mmol/L and 2-hr PG <7.8 mmol/L. Intention-to-treat and on-treatment analyses were conducted using Poisson regression models, overall and for subgroups (age, sex, CHD type, HbA<sub>1c</sub>, FPG, 2h-PG, BMI eGFR), for IGT alone and for IGT+IFG, and for use of thiazides, ACE inhibitors/angiotensin receptor blockers, beta blockers, calcium channel blockers or statins). </p> <p>RESULTS</p> <p>Incident diabetes was less frequent with acarbose, compared with placebo, being 3.2 and 3.8 <i>per</i> 100 person-years respectively (rate ratio (RR) 0.82, 95%CI 0.71–0.94, p=0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose, compared with placebo, being 16.3 and 14.1 <i>per</i> 100 person-years respectively (RR 1.16, 95%CI 1.08–1.25, p<0.0001). This effect was greater in participants not taking an ACEi or ARB (RR 1.36, 95%CI 1.21–1.53; P<sub>interaction</sub>=0.0006). The likelihood of remaining in normoglycemic regression did not differ between acarbose and placebo groups (P=0.41).</p> <p>CONCLUSIONS</p> <p>Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD. </p>

Abstract P041: Serum Magnesium and the Incidence of Coronary Heart Disease Over 20 Years of Follow-up: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Mary R Rooney ◽  
Jeffrey R Misialek ◽  
Alvaro Alonso ◽  
Aaron R Folsom ◽  
Erin D Michos ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Proportional Hazards ◽  
Serum Magnesium ◽  
A Priori ◽  
Cox Proportional Hazards ◽  
Chd Risk ◽  
Chd Risk Factors ◽  
Aric Study

Introduction: Low serum magnesium (Mg) levels have been associated with increased coronary heart disease (CHD) risk, likely acting through pathways such as hypertension, hyperglycemia or inflammation. An early (1998) ARIC paper evaluated this association, based on 319 events, and identified a sex-interaction whereby the inverse Mg-CHD association was stronger among women than men. Nearly 2,000 events have occurred since the prior publication. Hence, we sought to update the analysis. Hypothesis: We hypothesized serum Mg would be inversely and independently associated with long-term risk of CHD. Methods: A total of 14,465 ARIC study participants without CHD at visit 1 (baseline) were included. Serum Mg was measured at visit 1 (1987-89) and visit 2 (1990-92). Incident CHD events were identified through 2014 using annual telephone calls, hospital discharge lists and death certificates, and were adjudicated by physician review. Multivariable Cox proportional hazards regression models were used. Serum Mg was categorized into quintiles based on mean visit 1 and 2 concentrations. Based on prior findings in ARIC suggesting an interaction, we decided a priori to provide sex-stratified results. Results: Participants at baseline were mean±SD age 54±6y, 57% were women and 27% black. Serum Mg was 1.62±0.14 mEq/L overall, 1.62±0.14 mEq/L among women and 1.63±0.14 mEq/L among men. Over a median follow-up of 25 years, 1,939 CHD cases were identified. Overall, serum Mg was inversely and monotonically associated with CHD risk after adjustment for demographics, lifestyle factors and other CHD risk factors (Table, p-trend<0.001). The association was stronger among women (HR Q5 vs Q1=0.63) than men (HR=0.83), but the sex-interaction was not statistically significant (p>0.05). Conclusions: In this large community-based cohort, serum Mg was inversely associated with CHD risk. This association was slightly stronger among women than men. Further research is needed to understand if increasing Mg levels is a useful target for CHD prevention.

scholarly journals Effect of β-blockers on the risk of COPD exacerbations according to indication of use: The Rotterdam study

2021 ◽  
pp. 00624-2020
Author(s):  
Leila Karimi ◽  
Lies Lahousse ◽  
Phebe De Nocker ◽  
Bruno H. Stricker ◽  
Guy G. Brusselle ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cox Proportional Hazards ◽  
Rotterdam Study ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
Β Blockers

Observational studies report a reduction of COPD exacerbations in patients treated with β-blockers. In contrast, the BLOCK COPD RCT which excluded COPD patients with cardiovascular (CV) conditions showed an increase in COPD exacerbations. It is unclear whether this discrepancy could be explained by underlying CV comorbidity. We examined whether the association between use of β-blockers and risk of COPD exacerbations differed between patients with and without a CV indication for β-blockers use.Within the Rotterdam Study, we followed COPD subjects until the first COPD exacerbation, or end of follow-up. Cardiovascular indication for β-blocker use was defined as a history of hypertension, coronary heart disease, atrial fibrillation, or heart failure at baseline. The association between β-blockers use and COPD exacerbations was assessed using Cox proportional hazards models adjusted for age, sex, smoking, incident CV disease (i.e., heart failure, hypertension, atrial fibrillation, and coronary heart disease during follow-up), respiratory drugs, and nitrates.In total 1312 COPD patients with a mean age=69.7±9.2 years were included. In patients with a CV indication (n=755, mean age=70.4±8.8 years), current use of cardioselective β-blockers was significantly associated with a reduced risk of COPD exacerbations (HR=0.69, 95% CI: 0.57–0.85). In contrast, in subjects without a CV indication (n=557, mean age=68.8±9.7 years), cardioselective β-blockers was not associated with an altered risk of COPD exacerbations (HR=0.94, 95% CI: 0.55–1.62).Use of cardioselective β-blockers reduced the risk of exacerbations in COPD patients with concomitant cardiovascular diseases. Therefore, the potential benefits of β-blockers might be confined to COPD patients with cardiovascular disease.

Abstract 11: Prospective Association of Tet2 Mediated Clonal Hematoopoiesis and Heart Failure and Its Subtypes in Postmenopausal Women

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Chuck Eaton ◽  
Laura M Raffield ◽  
Alexander Bick ◽  
Mary Roberts ◽  
Joann E Manson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Ejection Fraction ◽  
Postmenopausal Women ◽  
Somatic Mutations ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

Background: Recent studies have shown that hematopoietic stems cells can undergo clonal expansion secondary to somatic mutations, termed clonal hematopoiesis of indeterminate potential (CHIP). TET2 is frequently mutated in individuals with CHIP and has been associated with coronary heart disease in humans and Heart Failure in mice models. We investigated whether any of the top three somatic mutations ( DNMT3A,TET2, ASXL1) associated with CHIP were prospectively associated with heart failure (HF), heart failure with preserved ejection fraction (HFPEF) or heart failure with reduced ejection fraction (HFrEF) in post menopausal women. Methods: A subcohort of 5214 postmenopausal women in the Women’s Health Intiative were evaluated for CHIP and HF. CHIP was determined at the Broad Institute via whole genome sequencing using the GATK4 MuTect2 somatic variant caller through the NHLBI TOPMed project. Hospitalized heart failure was based upon trained physician record review. HFpEF was defined as an EF > 50% and HFrEF as EF<50% . Cox proportional hazards model were evaluate adjusting for age, race, income, education, cigarette smoking, body mass index, coronary heart disease, atrial fibrillation, diabetes , hypertension, systolic blood pressure, and stroke. Inverse probability weighting was used to account for selection bias associated with the subcohort selection. Results: Of the 5214 postmenopausal women, 597 developed HF, 283 HFpEF and 204 HFrEF. N=408 had CHIP. The top 3 gene mutations associated with CHIP (N=364) were DNMT3A (4.8%), TET2 (1.7%) and ASXL1 (0.5%). Women with CHIP associated with any of the top 3 mutations and with TET2 were associated with HF, HFpEF but not HFrEF. DNMT3A and ASXL1 CHIP mutations were not associated HF, HFpEF or HFrEF (See Table ). Conclusion: CHIP associated with the top 3 somatic mutations and TET2 were prospectively associated with HF and HFpEF consistent with animal models and the concept of HFpEF being associated with pathologic aging. Replication of these findings in other cohorts is warranted.

scholarly journals Impact of Acarbose on Incident Diabetes and Regression to Normoglycemia in People with Coronary Heart Disease and Impaired Glucose Tolerance: Insights from the ACE Trial

2020 ◽  
Author(s):  
Hertzel C. Gerstein ◽  
Ruth L. Coleman ◽  
Charles A.B. Scott ◽  
Shishi Xu ◽  
Jaakko Tuomilehto ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Multiple Testing ◽  
Angiotensin Receptor Blockers ◽  
Incident Diabetes ◽  
Channel Blockers ◽  
Cardiovascular Evaluation ◽  
The Impact

OBJECTIVE <p>We examined the impact of acarbose, an alpha-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD).</p> <p>RESEARCH DESIGN AND METHODS</p> <p>Participants were randomly assigned to acarbose or placebo and followed with four-monthly FPGs and annual OGTTs. Incident diabetes was defined as two successive diagnostic FPGs ≥ 7 mmol/L or 2-hr PGs ≥ 11.1 mmol /L while taking study medication, or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG <6.1 mmol/L and 2-hr PG <7.8 mmol/L. Intention-to-treat and on-treatment analyses were conducted using Poisson regression models, overall and for subgroups (age, sex, CHD type, HbA<sub>1c</sub>, FPG, 2h-PG, BMI eGFR), for IGT alone and for IGT+IFG, and for use of thiazides, ACE inhibitors/angiotensin receptor blockers, beta blockers, calcium channel blockers or statins). </p> <p>RESULTS</p> <p>Incident diabetes was less frequent with acarbose, compared with placebo, being 3.2 and 3.8 <i>per</i> 100 person-years respectively (rate ratio (RR) 0.82, 95%CI 0.71–0.94, p=0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose, compared with placebo, being 16.3 and 14.1 <i>per</i> 100 person-years respectively (RR 1.16, 95%CI 1.08–1.25, p<0.0001). This effect was greater in participants not taking an ACEi or ARB (RR 1.36, 95%CI 1.21–1.53; P<sub>interaction</sub>=0.0006). The likelihood of remaining in normoglycemic regression did not differ between acarbose and placebo groups (P=0.41).</p> <p>CONCLUSIONS</p> <p>Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD. </p>

2436-PUB: Predicting Risk for New-Onset Type 2 Diabetes in Chinese People with Coronary Heart Disease and Impaired Glucose Tolerance

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2436-PUB
Author(s):  
SHISHI XU ◽  
CHARLES A. SCOTT ◽  
RUTH L. COLEMAN ◽  
JAAKKO TUOMILEHTO ◽  
RURY R. HOLMAN
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Chinese People ◽  
Onset Type ◽  
New Onset

Abstract P316: Prehypertension and Incident Acute Coronary Heart Disease in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Stephen P Glasser ◽  
Yulia Khodneva ◽  
Daniel Lackland ◽  
Ronald Prineas ◽  
Monika Safford
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Racial Differences ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Community Dwelling ◽  
Cox Proportional Hazards Models ◽  
Chd Risk ◽  
Regards Study ◽  
Chd Risk Factors

Objective: The independent prognostic value of prehypertension (preHTN) for incident coronary heart disease (CHD) remains unsettled. Using the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study, we examined associations between preHTN and incident acute CHD and CVD death. Methods: REGARDS includes 30,239 black and white community-dwelling adults age 45 and older at baseline. Recruitment occurred from 2003-7, with baseline interviews and in-home data collection for physiologic measures. Follow-up is conducted by telephone every 6 months to detect events and deaths, which are adjudicated by experts. Systolic BP was categorized into <120 mmHg (n=4385), 120-129 mmHg (n=4000), 130-139 (n=2066), and hypertension was categorized into controlled (<140/90 mmHg on treatment) (n=8378), and uncontrolled (>140/90 mmHg) (n=5364). Incident acute CHD was defined as definite or probable myocardial infarction (MI) or acute CHD death. CVD death was defined as acute CHD, stroke, heart failure or other cardiovascular disease related. Cox proportional hazards models estimated the hazard ratios (HR) for incident CHD by BP categories, adjusting for sociodemographics and CHD risk factors. Results: The 23,393 participants free of CHD at baseline were followed for a median of 4.4 years. Mean age was 64.1, 58% were women and 42% were black. There was a significant interaction between sex and BP categories, therefore analyses were stratified by sex. There were 252 non-fatal and fatal acute CHD events among women and 407 among men. Among women, compared with SBP<120 mmHg, BP categories above SBP 120 mmHg were associated with incident CHD (adjusted HR for SBP120-129 mmHg=1.94 {95% CI 1.04-3.62]; SBP 130-139 mmHg=1.92 {0.95-3.87}; controlled HTN=2.16 {1.25-3.75}; uncontrolled HTN=3.25 {1.87-5.65}) in fully adjusted models. Among men, only uncontrolled HTN was associated with incident CHD (HR=1.55 {1.11-2.17}). Conclusion: In this sample, preHTN may be associated with incident CHD among women but not men.

Abstract MP53: Consumption Of Ultra-processed Food Is Associated With Risk Of Coronary Heart Disease In The Atherosclerosis Risk In Communities Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Shutong Du ◽  
Hyunju Kim ◽  
Josef Coresh ◽  
Casey M Rebholz
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Food Intake ◽  
Proportional Hazards ◽  
Sociodemographic Factors ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Processed Food ◽  
Cox Proportional Hazards Models ◽  
Food And Drink

Introduction: Ultra-processed food defined as food and drink products formulated through sequences of industrial processes, and generally contain non-culinary used additives. Previous studies have linked higher ultra-processed food intake with several cardiometabolic and cardiovascular diseases. However, longitudinal evidence from US populations remains scarce. Hypothesis: We hypothesized that higher intake of ultra-processed food is associated with higher risk of coronary heart disease (CHD). Methods: We selected 12,607 adults aged 44-66 years in 4 US communities from the ARIC study at baseline. Dietary intake data were collected through a validated 66-item food frequency questionnaire. Ultra-processed foods were defined using the NOVA classification and the level of intake was calculated for each participant. We conducted Cox proportional hazards models to study the association between quartiles of ultra-processed food intake and incident CHD. Nonlinearity was assessed by using restricted cubic spline regression. Results: There were 1,899 incident CHD cases documented after an median follow up of 27 years (291,285.2 person-years). Incidence rates were higher in the highest quartile of ultra-processed food intake (71.6 per 10,000 person-years; 95% CI, 65.8-78.0) compared to the lowest quartile (59.7 per 10,000 person-years; 95% CI, 54.3-65.7). Participants in the highest vs. lowest quartile were associated with a 18% higher risk of CHD (Hazard ratio 1.18 [95% CI, 1.04 - 1.34]; P-trend = 0.010) after adjusting for sociodemographic factors and health behaviors. An approximately linear relationship was observed between ultra-processed food intake and risk of CHD after 4 servings/day ( Figure ). Conclusion: In conclusion, higher ultra-processed food intake was associated with a higher risk of coronary heart disease among middle-aged US adults. Further prospective studies are needed to confirm these findings and to investigate the mechanisms by which ultra-processed food may affect health.

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