Clinical Clinical Coronary Artery Disease Research Articles

The association of sex-specific hormones with coronary artery plaque characteristics from Miami Heart (MiHeart) study

ObjectiveThe association of sex-specific hormones with coronary computed tomography angiography(CCTA)-based plaque characteristics in women without cardiovascular disease is not well understood. We investigated the association of sex-specific hormones with coronary artery plaque characteristics in a contemporary multiracial cohort with no clinical coronary artery disease (CAD). MethodsIn this cross-sectional analysis, we utilized data from 2,325 individuals with no clinical CAD from the Miami Heart (MiHeart) study. Multivariable logistic regression models were used to investigate the association of sex hormones: sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), free and total testosterone, estradiol, with plaque characteristics among women and men. ResultsOf the 1,155 women, 34.2% had any plaque and 3.4% had any high-risk plaque features (HRP) while among men (n = 1170), 63.1% had any plaque and 10.4% had HRP. Among women, estradiol and SHBG were associated with lower odds of any plaque after adjusting for age and race-ethnicity (estradiol OR per SD increase: 0.87, 95%CI: 0.76–0.98; SHBG OR per SD increase: 0.82, 95%CI: 0.72–0.93) but the significance did not persist after adjustment of cardiovascular risk factors. High free testosterone was associated with higher odds of HRP (aOR:3.48, 95%CI:1.07–11.26) but null associations for the other sex hormones with HRP, in the context of limited sample size. Among men, there were no significant associations between sex-specific hormones and plaque or HRP. ConclusionAmong young to middle-aged women with no clinical CAD, increasing estradiol and SHBG were associated with lower odds of any plaque and higher free testosterone was associated with HRP. Larger cohorts may be needed to validate this.

Comparison of Lipoprotein(a)-Levels in Patients ≥70 Years of Age With Versus Without Aortic Valve Stenosis

Although lipoprotein(a) (Lp[a]) is linked with aortic valve calcification and clinical aortic valve stenosis (AVS) in middle-aged cohorts, patients aged ≥70 years represent a majority of patients with AVS, in which mechanisms leading to AVS may differ. We sought to determine whether Lp(a) distinguishes patients ≥70 years with and without AVS. We matched 484 patients ≥70 years with AVS, scheduled for transcatheter aortic valve implantation with 484 patients without AVS by age group and gender. Lp(a) levels were compared in patients with and without AVS and stratified by presence and absence of clinical coronary artery disease (CAD) manifestation. A total of 968 patients (mean age 80 ± 5 years, 48% women) were included. When comparing patients with and without AVS, no difference in Lp(a) was observed (AVS: 17 [8; 56] mg/dl, no AVS: 18.5 [8.5; 57] mg/dl, p = 0.56). In contrast, patients with clinical CAD manifestation had higher Lp(a) levels than those without clinical CAD manifestation (coronary artery disease: 19 [9; 60] mg/dl, no coronary artery disease 15 [7; 44] mg/dl, p = 0.0006). In regression analysis, no significant association of Lp(a) with AVS was observed in unadjusted (OR [95% CI]: 0.98 [0.91 to 1.06], p = 0.59) and risk factor-adjusted models (0.98 [0.90 to 1.06], p = 0.57). However, Lp(a) was independently associated with clinical CAD manifestation (unadjusted: 1.14 [1.04 to 1.24], p = 0.003, risk factor adjusted: 1.17 [1.07 to 1.27], p = 0.0006). In conclusion, in a large cohort of patients ≥70 years, Lp(a) was associated with clinical CAD manifesation, but not with AVS. Our results suggest that in patients over 70 years, the development of AVS is not influenced by Lp(a).

Type 1 diabetes: Developing the first risk-estimation model for predicting silent myocardial ischemia. The potential role of insulin resistance

ObjectivesThe aim of the study was to develop a novel risk estimation model for predicting silent myocardial ischemia (SMI) in patients with type 1 diabetes (T1DM) and no clinical cardiovascular disease, evaluating the potential role of insulin resistance in such a model. Additionally, the accuracy of this model was compared with currently available models for predicting clinical coronary artery disease (CAD) in general and diabetic populations.Research, design and methodsPatients with T1DM (35–65years, >10-year duration) and no clinical cardiovascular disease were consecutively evaluated for: 1) clinical and anthropometric data (including classical cardiovascular risk factors), 2) insulin sensitivity (estimate of glucose disposal rate (eGDR)), and 3) SMI diagnosed by stress myocardial perfusion gated SPECTs.ResultsEighty-four T1DM patients were evaluated [50.1±9.3 years, 50% men, 36.9% active smokers, T1DM duration: 19.0(15.9–27.5) years and eGDR 7.8(5.5–9.4)mg·kg-1·min-1]. Of these, ten were diagnosed with SMI (11.9%). Multivariate logistic regression models showed that only eGDR (OR = -0.593, p = 0.005) and active smoking (OR = 7.964, p = 0.018) were independently associated with SMI. The AUC of the ROC curve of this risk estimation model for predicting SMI was 0.833 (95%CI:0.692–0.974), higher than those obtained with the use of currently available models for predicting clinical CAD (Framingham Risk Equation: 0.833 vs. 0.688, p = 0.122; UKPDS Risk Engine (0.833 vs. 0.559; p = 0.001) and EDC equation: 0.833 vs. 0.558, p = 0.027).ConclusionThis study provides the first ever reported risk-estimation model for predicting SMI in T1DM. The model only includes insulin resistance and active smoking as main predictors of SMI.

Abstract P188: “False Positive” Stress Testing: Does Endothelial Vascular Dysfunction Explain ST-Segment Depression in the Absence of Clinical Coronary Artery Disease in Women?

Background: Current guidelines do not endorse exercise electrocardiography (Ex-ECG) screening in asymptomatic adults due to poor diagnostic accuracy for clinical coronary artery disease (CAD), however Ex-ECG combined with other variables paradoxically has strong prognostic accuracy for cardiovascular mortality. Ex-ECG ST segment depression “false positive” results are common in women, who have higher rates of vascular dysfunction such as Raynaud’s and migraines compared to men. We hypothesized that ST segment depression indicates endothelial vascular dysfunction, which is known to predict an adverse prognosis. To test this hypothesis, we evaluated the relationship between Ex-ECG and peripheral endothelial vascular function in asymptomatic women. Methods: Asymptomatic women with no cardiac risk factors and normal resting ECG underwent maximal Bruce protocol Ex-ECG testing (GE Healthcare). Computer-generated Ex-ECG ST segment values were independently verified by 2 cardiologists. Based on established methods, endothelial vascular function was assessed by calculating reactive hyperemia index (RHI) using peripheral vascular testing (Endopat, Itamar). As established previously, RHI <1.68 is abnormal and indicates endothelial vascular dysfunction. Results: Among 35 women, mean age 54±8 years and BMI 24±4, there were 5 (14%) women with abnormal RHI. Women with abnormal RHI had a greater (more abnormal) ST/HR slope, a trend toward greater peak ST depression, and achieved lower METs than women with normal RHI (Table 1). Conclusion: Among asymptomatic women, endothelial vascular dysfunction was associated with abnormal Ex-ECG results characterized by greater ST/HR slope, greater ST depression, and lower exercise capacity. These findings suggest that “false positive” ST-segment depression in the absence of clinical CAD in women may be explained by endothelial vascular dysfunction. Our study further suggests that endothelial vascular dysfunction may explain the Ex-ECG diagnostic/prognostic paradox.

Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies

We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.

Are Retinal Microvascular Caliber Changes Associated with Severity of Coronary Artery Disease in Symptomatic Cardiac Patients?

Recent population-based studies have shown that retinal vascular caliber may predict the risk of clinical coronary artery disease (CAD) events. Whether this association is related to macro- or microvascular mechanisms remains unknown. We investigated the relationship of retinal vascular caliber with severity and extent of CAD in symptomatic cardiac patients. Overall, 98 patients attending diagnostic coronary angiography were recruited. Coronary angiography was used to assess for the severity and extent of CAD. Digital retinal photography was performed immediately prior to cardiac catheterization, and retinal vascular caliber was measured from these photographs by using a computer program and summarized as central retinal arteriolar (CRAE) and venular (CRVE) equivalents. Retinal arteriolar and venular calibers were not associated with increasing severity of CAD, as assessed by Leaman scores (CRAE/CRVE: P for trend=0.17/0.57), presence of clinically significant CAD (CRAE/CRVE: P=0.35/0.32), or number of diseased vessels (CRAE/CRVE: P for trend=0.18/0.69). Retinal vascular caliber changes are not associated with the severity of obstructive CAD in symptomatic patients. These data suggest that the association of retinal vascular caliber with clinical CAD seen in epidemiological studies may not be applicable to clinical symptomatic patients and may be related to microvascular, rather than macrovascular, mechanisms.

Abstract 3126: Coronary Artery Calcification as a Predictor of Subsequent Coronary Artery Disease Events

Coronary artery calcification (CAC) as measured by electron beam computed tomography (EBCT) can be used as an indicator of atherosclerotic burden. We have previously reported a cross sectional association between the presence of CAC and history of clinical coronary artery disease (CAD) in type 1 diabetes. In this analysis, we assessed the ability of CAC to predict the incidence of CAD events. Participants from the Pittsburgh Epidemiology of Diabetes Complications Study of childhood onset type 1 diabetes who underwent an EBCT screening (1996–98) and were free of clinical CAD were selected for study (n=236). Mean age at EBCT screening was 36.6 years and diabetes duration 28 years. CAC was calculated using the Agatston score and was used both as a continuous variable (after log transformation) and as a categorical variable. CAD was defined as non-fatal MI (n=4), ischemic ECG changes (Minnesota codes 1.3, 4.1, 4.2, 4.3, 5.1, 5.2, 5.3, 7.1) (n=9), hospitalized unstable angina (n=1), new onset angina leading to revascularization (n=2) or fatal CAD (n=4). Glucose disposal rate (eGDR-insulin sensitivity) was estimated by a regression equation derived from hyperinsulinemic euglycemic clamp studies with terms for waist to hip ratio, HbA 1c , and hypertension. During a mean follow-up of 7.4 years, 20 (8.5%) individuals had an incident event. Individuals who had an event were older, with a greater diabetes duration, systolic blood pressure, HbA 1c , and WBC count, a lower eGDR (all p-values <0.05), and a higher CAC score (p<0.0001). Thus, approximately 24% of persons with CAC ≥200 had a subsequent CAD event compared to only 3% of those with a zero score. In multivariable Cox proportional hazard models with backward elimination, a CAC score greater than zero was a significant predictor of CAD incidence (HR=4.07, 95% CI=1.38–11.96). Other significant predictors comprised diabetes duration (HR=1.07, 95% CI=1.01–1.14) and HbA 1c (HR=1.39, 95% CI=1.10–1.76). The area under the ROC curve increased from 0.720 to 0.784 with the inclusion of CAC score. In this cohort of individuals with type 1 diabetes, CAC is a significant predictor of subsequent CAD status and adds to the prediction beyond standard risk factors. Thus, CAC may be used as a screening tool for CAD risk in type 1 diabetes.

Prognostic impact of diabetes mellitus in patients with heart failure and preserved ejection fraction: a prospective five-year study

Objective:To evaluate the prognostic impact of diabetes mellitus (DM) in patients with heart failure and preserved ejection fraction (HFPEF)Design:A five-year prospective observational studySetting:Population of 368 consecutive patients from 11 healthcare...

Diabetes in Heart Failure: Prevalence and Impact on Outcome in the Population

Purpose Little is known on the prevalence and prognostic importance of diabetes mellitus (DM) among individuals with heart failure (HF) in community-based cohorts. Methods Within Olmsted County, Minnesota, a random sample of all subjects with a first diagnosis of HF between 1979 and 1999 was validated using Framingham criteria. DM was validated using glycemic criteria. Results Among 665 subjects with HF (mean age 77 ± 12 years, 46% male), 20% had prior DM. Subjects with DM were younger, had greater body mass index (BMI), and lower left ventricular ejection fraction than subjects without diabetes. The prevalence of DM increased markedly over time (3.8% per year; 95% confidence interval [CI], 0.8 to 6.9; P = .024), independently of BMI, particularly in older subjects (odds ratio of having DM in 1999 compared with 1979 was 3.93 [95% CI, 1.57 to 9.83] in subjects ≥75 years vs. 1.11 [95% CI, .40 to 3.05] in subjects <75 years). Five-year survival was 37% among subjects with DM versus 46% among subjects without ( P = .017). The risk of death associated with DM differed markedly according to clinical coronary artery disease (CAD) ( P = .025). Subjects with DM and no CAD had a higher risk of death (relative risk [RR] = 1.79 [95% CI, 1.33 to 2.41]) than those with CAD (RR = 1.11 [95% CI, .81 to 1.51]), independently of age, sex, BMI, renal function, calendar year of HF, comorbidity and EF. Conclusions Among community-dwelling patients with HF, the prevalence of DM increased markedly over time. DM is associated with a large increase in mortality, particularly among subjects without clinical CAD, underscoring the importance of aggressive management of DM in HF.

Alcohol intake is not associated with subclinical coronary atherosclerosis

Background The inverse relation between alcohol intake and clinical coronary artery disease (CAD) is well established, although the mechanisms remain speculative. We studied the relation between alcohol intake and subclinical CAD to assess the possible role of alcohol in atherogenesis. Methods We conducted a prospective study of 731 consecutive, consenting, active-duty US Army personnel (39 to 45 years of age) without known CAD who were undergoing a routine physical examination. Each participant was surveyed with the validated Block dietary questionnaire, which included detailed information on alcohol intake as wine, beer, or liquor. Subclinical CAD was determined by means of electron beam computed tomography to quantify coronary artery calcification (CAC). Results The mean age was 42 (±2); 83% were male, 71% were white, and 82% were college graduates. The prevalence of CAC was 18.6% (mean CAC score = 12 ± 69). Twenty-two percent drank alcohol daily, with an average of 2.4 drinks per day. Systolic blood pressure was correlated with number of drinks per day ( r = 0.10, P = .025). Among drinkers, HDL was weakly correlated with daily alcohol consumption ( r = 0.10, P = .025). There was no relation between the CAC score and the alcohol intake as measured by drinks per day (OR, 1.02; 95% CI, 0.64 to 1.63; 1.13, 0.59 to 2.15; 1.26, 0.69 to 2.59, for less than 1, 1 to 2, and more than 2 drinks per day, respectively). Stratified analyses based on type of alcohol and multivariate analyses indicated no independent relation between any type or quantity of alcohol intake and the presence or extent of coronary calcification. Conclusions Alcohol intake does not appear to be inversely related to subclinical CAC, implying that previous observations of a protective effect of alcohol on clinical CAD may involve factors related to plaque stability rather than atherogenesis.

Consequences of diabetes: cardiovascular disease.

This is the third of three articles dealing with the International Diabetes Federation meeting, which was held in Paris, 24–29 August 2003. Paul Valensi (Bobigny, France) discussed approaches to silent myocardial ischemia in persons with diabetes. Addressing the question of whether it is in fact advisable to detect cardiovascular disease (CVD) in persons without history of myocardial infarction or angina, he noted the poor prognosis of persons with diabetes, whose risk of myocardial infarction in the absence of CVD is similar to that of persons without diabetes and with a prior myocardial infarction. Those having evidence of CVD are at particularly increased risk, with half dying within 8 years (1). One-year mortality after thrombolysis is increased by half in persons with diabetes, and survival of persons without diabetes who have had a second myocardial infarction is similar to that of those with diabetes after an initial event (2). The prevalence at autopsy of high grade and multilevel coronary atherosclerosis in diabetic individuals without clinical coronary artery disease (CAD) is similar to that of persons without diabetes with clinical CAD, both for males and for females (3). In a French multicenter study of 417 asymptomatic diabetic persons with at least two additional risk factors undergoing thallium scintigraphy with exercise or dipyridamole, 162 had positive nuclear study, and of 70 having angiography, 39 were found to have evidence of CAD, a positive predictive value of only 56%. Other studies suggest that approximately one-third of asymptomatic persons with diabetes have a positive screening test, but that only approximately one-third of these have positive results on angiography, suggesting poor correlation between functional and morphological abnormality. Alternatively, Valensi suggested, scintigraphy may actually be more sensitive than angiography to the presence of CAD, noting that there certainly is evidence that an abnormal study is associated with …

Relation of C-reactive protein and other cardiovascular risk factors to penile vascular disease in men with erectile dysfunction.

Erectile dysfunction (ED) may be an early sign or symptom of cardiovascular disease (CVD). We examined the relation of traditional and emerging risk factors for CVD to the severity of penile vascular disease in men with ED and without clinical coronary artery disease (CAD). In total, 137 men with ED were evaluated for penile vascular disease severity by penile Doppler ultrasound. These men were divided into the following groups based on ultrasound results: normal, cavernous venous occlusive disease, mild arterial insufficiency, and severe arterial insufficiency. Traditional (fasting lipid panel, fasting glucose, age, BMI, smoking, Framingham coronary artery disease risk score) and emerging (C-reactive protein, Lp(a), homocysteine) risk factors for CVD were correlated to severity of penile vascular disease in men with ED and without clinical CAD. Using univariate analysis, penile Doppler groups showed significant positive correlation to CRP (r=0.21; < or = 0.05) and age (r=0.30; < or = 0.01). For CRP, this correlation remained significant even when adjusted for age (< or = 0.05). Men displaying evidence of penile arterial disease (mild and severe arterial insufficiency) were characterized by elevated CRP levels (0.17 mg/dl) compared to men with no evidence of arterial abnormalities in the penis (0.04 mg/dl). CRP levels correlate significantly with increasing severity of penile vascular disease as measured by penile Doppler.

Coronary atherosclerosis in diabetes mellitus: A population-based autopsy study

ObjectivesThe study was conducted to test the hypothesis that the prevalence of coronary atherosclerosis is greater among diabetic than among nondiabetic individuals and is similar for diabetic individuals without clinical coronary artery disease (CAD) and nondiabetics with clinical CAD. BackgroundPersons with diabetes but without clinical CAD encounter cardiovascular mortality similar to nondiabetic individuals with clinical CAD. This excess mortality is not fully explained. We examined the association between diabetes and coronary atherosclerosis in a geographically defined autopsied population, while capitalizing on the autopsy rate and medical record linkage system available via the Rochester Epidemiology Project, which allows rigorous ascertainment of coronary atherosclerosis, clinical CAD, and diabetes. MethodsUsing two measures, namely a global coronary score and high-grade stenoses, the prevalence of atherosclerosis was analyzed in a cohort of autopsied residents of Rochester, Minnesota, age 30 years or older at death, while stratifying on diabetes, clinical CAD diagnosis, age, and gender. ResultsIn this cohort, diabetes was associated with a higher prevalence of atherosclerosis. Among diabetic decedents without clinical CAD, almost three-fourths had high-grade coronary atherosclerosis and more than half had multivessel disease. Without diabetes, women had less atherosclerosis than men, but this female advantage was lost with diabetes. Among those without clinical CAD, diabetes was associated with a global coronary disease burden and a prevalence of high-grade atherosclerosis similar to that observed among nondiabetic subjects with clinical CAD. ConclusionsThese findings provide mechanistic insights into the excess risk of clinical CAD among diabetic individuals, thereby supporting the need for aggressive prevention of atherosclerosis in all diabetic individuals, irrespective of clinical CAD symptoms.

Coronary calcium in adults with type 1 diabetes: a stronger correlate of clinical coronary artery disease in men than in women.

We studied the relationship of coronary artery calcification (CAC), a marker of coronary atherosclerosis, with prevalent clinical coronary artery disease (CAD) and established cardiovascular disease (CVD) risk factors in a type 1 diabetic population. At the 10-year follow-up examination of the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study cohort, 302 adults (mean age 38.1 +/- 7.8 years) received electron beam tomography (EBT) scanning of the heart and a clinical examination. Clinical CAD was defined as a confirmed history of myocardial infarction (MI), angiographic stenosis > or =50%, Pittsburgh EDC Study physician-diagnosed angina, or ischemic electrocardiogram (ECG). CAC correlated with most CVD risk factors. CAC had 84 and 71% sensitivity for clinical CAD in men and women, respectively, and 100% sensitivity for MI or obstructive CAD. A CACS cut point of 400 was the most efficient coronary calcium correlate of CAD. In subjects with angina only, CAC sensitivity was 83% in men and 46% in women. In logistic regression, CAC, ECG R-R variation, peripheral vascular disease, and Beck Depression Inventory independently correlated with prevalent CAD in men and overall. Except for CAC, the same variables independently correlated with CAD in women, and age also entered the model. CAC was an independent correlate of MI or obstructive CAD in both sexes and was the strongest independent correlate in men, but CAC was not independently associated with angina and ischemic ECG in either sex. It is concluded that EBT-detected CAC is strongly correlated with CAD in type 1 diabetes-particularly in men.

Carotid artery atherosclerosis in type-2 diabetic and nondiabetic subjects with and without symptomatic coronary artery disease (The Insulin Resistance Atherosclerosis Study)

Type-2 diabetes mellitus is associated with a 2- to 4-fold increase in the risk of clinical coronary artery disease (CAD). It has been suggested that diabetic subjects without clinical CAD should be treated as aggressively for cardiovascular risk factors as subjects with CAD. This would be warranted if diabetic subjects without clinical CAD would have accelerated CAD similar to that of nondiabetic subjects with symptomatic CAD. To assess this suggestion, we compared the intima-media wall thickness in the common carotid artery (CCA) and internal carotid artery (ICA) in 43 diabetic subjects with clinical CAD, 446 diabetic subjects without clinical CAD, 47 nondiabetic subjects with clinical CAD, and 975 nondiabetic subjects without clinical CAD (all aged 40 to 70 years) in the Insulin Resistance Atherosclerosis Study. All data were adjusted for age, gender, ethnicity, and clinical results. Both diabetes and CAD were associated with increased atherosclerosis in the CCA. Likewise, diabetes was significantly associated with increased atherosclerosis in the ICA; however, CAD was not associated with ICA intima-media wall thickness. As expected, diabetic subjects with CAD had the greatest intima-media wall thickness, whereas nondiabetic subjects without CAD had the least atherosclerosis. Subjects with diabetes but without CAD had slightly greater intima-media wall thickness than nondiabetic subjects with CAD, although these differences were not statistically significant. Thus, diabetic subjects even without CAD had extensive atherosclerosis in the carotid artery. These results support the suggestion that diabetic subjects should be treated as aggressively for cardiovascular risk factor management as subjects with pre-existing CAD.