Familial aggregation of coronary artery calcium in families with type 2 diabetes

Type 2 diabetes is widely recognized as a major risk factor for atherosclerotic cardiovascular disease, including subclinical atherosclerosis as measured by noninvasive procedures. However, the role of genetic factors that contribute to various measures of subclinical atherosclerosis is largely unknown. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), will be extensive in individuals with type 2 diabetes and that its presence depends on both genetic and environmental factors. The genetic factors should result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122 individuals with type 2 diabetes (mean age 60 years) and 13 individuals without diabetes in 56 families. CAC was measured by fast-gated helical computed tomography. Other measured factors included blood pressure, body size, lipids, HbA1c, and self-reported medical history. To test for an association between CAC and these factors while accounting for the potential familial correlation of CAC, generalized estimating equations were used. CAC was detectable in 80% of individuals with diabetes (median score 84, range 0-5,776). Extent of CAC, adjusted for age, was positively associated with male sex (P = 0.0003), reduced HDL (P = 0.02), albumin-to-creatinine ratio (P = 0.008), and cigarette pack-years (P = 0.03). CAC was also positively associated with a history of angina, myocardial infarction, stroke, and vascular procedures (all P < 0.01). HbA1c and fasting glucose were positively, but nonsignificantly, associated with the extent of CAC (P = 0.14 and 0.08, respectively). CAC, adjusted for age, sex, race, and diabetes status, was heritable (h2 = 0.50; P = 0.009). In multivariate analysis with additional adjustment for HDL, BMI, hypertension, and smoking, h2 = 0.40 (P = 0.038). These results suggest that strong (independent) genetic factors as well as environmental factors contribute to the variance of CAC in individuals with type 2 diabetes. In these data, CAC seems heritable and may serve as an important feature in designing studies to map genes contributing to both atherosclerosis and type 2 diabetes.     

Lipoprotein subclasses and particle sizes and their relationship with coronary artery calcification in men and women with and without type 1 diabetes

Type 1 diabetes is associated with increased coronary atherosclerosis, especially in women, even though such patients often have an apparently normal lipid profile. We examined whether lipoprotein particle sizes and subclasses differed between type 1 diabetic subjects (n = 194, age 30-55 years) and age- and sex-matched control subjects (n = 195). We examined whether any abnormalities were of similar magnitude in men and women. The relationship of particle size to electron beam computer tomography-defined coronary artery calcification, a measure of atherosclerosis, was also examined. Proton nuclear magnetic resonance (NMR) spectroscopy was used to quantify VLDL, LDL, and HDL subclass levels and average particle size on fasting samples. LDL size and subclass were similar in diabetic and nondiabetic men. In contrast, in women diabetes was associated with less large and more small LDL and a reduced LDL size (mean difference 0.2 nm; P = 0.0009). This greater effect of diabetes on LDL size in women compared with men was significant (P = 0.007). Diabetes was associated with more large and less small HDL and, to a similar degree in both sexes, a higher HDL size (difference of 0.4 nm in men and 0.3 nm in women; both P < 0.0001). There were no definitive abnormalities in VLDL size. In nondiabetic subjects, lower average HDL particle size, lower LDL size, and higher VLDL size were significantly associated with coronary calcification (P = 0.001, 0.02, and 0.04, respectively). Thus the HDL size differences with diabetes would be expected to be antiatherogenic and the LDL size differences pro-atherogenic. However, there was no clear relationship between particle size and calcification in diabetic subjects. We conclude that in the general population NMR spectroscopy-derived particle size reveals important information about the atherogenicity of lipoprotein profile. Type 1 diabetes is associated with differences in NMR-derived particle size, but their pathogenic significance is unclear.     

Sexual function in women with coronary artery disease: a preliminary study

We investigated sexual function in female patients with coronary artery disease (CAD). A total of 20 consecutive female patients (38.2+/-3.8 years) with CAD diagnosed by coronary angiography and 15 healthy subjects (37.9+/-5.4 years) were enrolled in this study. The Female Sexual Function Index (FSFI) was used to assess sexual function in all the participants. Women with psychiatric disorders, gynecologic and systemic diseases that may affect sexual function were excluded from the study. The other exclusion criteria were usage of antidepressants and drugs affecting sexual function. Patients with CAD and healthy women were comparable in age, body mass index and education level. Female sexual dysfunction (FSD) was diagnosed in 12 of 20 women with CAD (60%), whereas five of 15 healthy women (33.3%) were found to have FSD (P<0.05). Patients with CAD had a significantly lower number of sexual intercourse episodes per month than healthy women volunteers (2.24 versus 5.2, respectively; P<0.05). The FSFI total score was clearly significantly decreased in the CAD group compared with that in healthy controls (17.8+/-2.9 and 26.0+/-4.8, P=0.001). When the subscores of each domain of FSFI were evaluated, all the subscores of FSFI, except the satisfaction domain, in patients with CAD were significantly lower than those of healthy subjects (P<0.05). This preliminary study demonstrates that female patients with CAD have distinct sexual dysfunction compared with healthy controls. Women with CAD should be evaluated also in terms of sexual function to provide better quality of life.     

Hypoglycemic counterregulatory responses differ between men and women with type 1 diabetes

The aim of this study was to determine whether sex-related differences occur in counterregulatory responses to hypoglycemia in adult type 1 diabetic patients. Experiments were carried out on 16 (8 men/8 women) type 1 diabetic patients and compared with 16 (8 men/8 women) age- and weight-matched normal individuals. Men and women with type 1 diabetes were matched for age (26+/-2 vs. 25+/-1 years), duration of diabetes (9+/-1 vs. 8+/-1 years), glycemic control (HbA1c 7.7+/-0.3 vs. 7.8+/-0.2%), and weight (BMI 22.8+/-1 vs. 22.1+/-1 kg/m2), respectively. After normalizing plasma glucose overnight, patients underwent a 2-h hyperinsulinemic-hypoglycemic clamp study. Plasma glucose (3.0+/-0.1 mmol/l) and insulin (510+/-48 pmol/l) levels were equated in all groups. Plasma epinephrine, norepinephrine, growth hormone (GH), muscle sympathetic nerve activity (MSNA), and endogenous glucose production (EGP) responses were significantly lower (P<0.01) in type 1 diabetic women compared with men. Autonomic symptom scores, lipid oxidation, nonesterified fatty acids (NEFAs), and glycerol responses were equivalent between men and women with type 1 diabetes despite significantly reduced sympathoadrenal and MSNA responses in women. Autonomic nervous system (ANS) and EGP responses were equivalent in type 1 diabetic and normal individuals. However, lipid oxidation (assessed by indirect calorimetry), glycerol, and NEFA responses were increased (P<0.01) in type 1 diabetic patients compared with normal control subjects. We conclude that counterregulatory responses to fixed hypoglycemia differ markedly in men and women with type 1 diabetes: 1) sympathetic nervous system, GH, and EGP responses are significantly reduced in type 1 diabetic women, 2) autonomic symptom awareness and lipolytic responses appear to be relatively increased in type 1 diabetic women compared with men, and 3) during conditions of similar hyperinsulinemic hypoglycemia and ANS drive, lipid oxidation and lipolytic responses can be increased in type 1 diabetic patients compared with normal individuals.     

Adiponectin and future coronary heart disease events among men with type 2 diabetes

Adiponectin, predominantly synthesized in the adipose tissue, seems to have substantial anti-inflammatory properties and to be a major modulator of insulin resistance and dyslipidemia, mechanisms that are associated with an increased atherosclerotic risk in diabetic patients. However, it is unknown whether higher levels of adiponectin are associated with a reduced risk for coronary heart disease (CHD) among diabetic individuals. We investigated the association between plasma adiponectin levels and incidence of CHD among 745 men with confirmed type 2 diabetes in the Health Professionals Follow-up Study. Participants were aged 46-81 years and were free of diagnosed cardiovascular disease at the time of blood draw in 1993/1994. During an average of 5 years of follow-up (3,980 person-years), we identified 89 incident cases of CHD (19 myocardial infarction and 70 coronary artery bypass surgery), confirmed by medical records. Levels of adiponectin were inversely associated with BMI and directly associated with age, alcohol intake, and duration of diabetes (P < 0.05). After adjustment for age, BMI, smoking, alcohol consumption, duration of diabetes, and other lifestyle factors, adiponectin was associated with a decreased risk for CHD events. The multivariate relative risk for CHD for a doubling of adiponectin was 0.71 (95% CI 0.53-0.95). Further adjustment for HDL cholesterol attenuated this association (0.78 [0.57-1.06]). The inverse association between adiponectin and CHD was consistent across strata of aspirin use, family history of myocardial infarction, alcohol consumption, insulin use, duration of diabetes, and levels of HbA(1c), triglycerides, C-reactive protein, and HDL cholesterol. Our study suggests that increased adiponectin levels are associated with a moderately decreased CHD risk in diabetic men. This association seems to be mediated in part by effects of adiponectin on HDL cholesterol levels.     

Coronary artery calcification is related to coronary atherosclerosis in chronic renal disease patients: a study comparing EBCT-generated coronary artery calcium scores and coronary angiography.

BACKGROUND: Coronary artery calcification (CAC) measured by electron beam computed tomography (EBCT) correlates with plaque burden, vessel stenosis and is predictive of future cardiac events in the general population. Extensive CAC has been described recently in dialysis cohorts. For the first time we studied the relationship between CAC and coronary angiographic findings in patients with chronic renal failure, on dialysis and after renal transplantation. METHODS: We studied 46 patients who all had an EBCT-derived Agatston coronary calcium score and a diagnostic coronary angiogram within a 12-month period. The mean age was 55.7+/-13.2 (SD) years (range 29-80). The mean duration of dialysis was 54.4 months (range 1-372). RESULTS: The mean CAC was 2370+/-352.8. The mean CAC in patients with an abnormal coronary angiogram (n = 35) was 2869.6+/-417.9, while that in patients with a normal coronary angiogram (n = 11) was 559.4+/-255.1 (P = 0.001 for the inter-mean comparison). Total CAC correlated with the number of diseased vessels (P = 0.0001) and with severity of atherosclerosis in all the vessels (P = 0.0001). The individual coronary artery calcification score correlated well with the severity of atherosclerotic coronary disease (P<0.0001 for all) in the left anterior descending, right coronary and circumflex arteries. Running a multivariate regression analysis for atherosclerosis burden, we found that the only predictor was CAC (r = 0.34, P = 0.0001). CONCLUSION: CAC is common and more severe in patients with chronic kidney disease. Although in chronic kidney disease patients CAC can occur in the absence of occlusive coronary atherosclerosis, our data suggest that, as in the general population, CAC in chronic kidney disease patients is associated with obstructive atherosclerosis and may therefore be associated with a worse outcome.     

Coronary artery bypass grafting in adults with congenital heart disease

Abstract Background: Adults with congenital heart disease (CHD) and coronary artery disease (CAD) have unique clinical manifestation due to the coexistence of intracardiac anomalies and CAD. Case reports are rare in surgical management of CHD combined with CAD. Our goal is to study the outcome of surgical intervention of CHD and CAD concomitantly. Methods: From February 2002 to August 2009, 29 adult patients underwent coronary artery bypass grafting (CABG) and surgical correction of CHD concomitantly. Congenital cardiac anomalies include atrial septal defect (ASD) in 21 cases, ventricular septal defect in four cases, atrioventricular septal defect in three cases, and cor triatriatum in one case. Coronary angiography demonstrated: one‐vessel disease in 10 cases, two‐vessel disease in 11 cases, and three‐vessel disease in eight cases. Coronary revascularization and intracardiac anomalies were corrected with cardiopulmonary bypass in 23 cases. There were six patients who had off‐pump coronary artery pass grafting (OPCAB) and intraoperative device closure of ASD. Results: One patient died of pulmonary infection and multiorgan failure. Follow‐up time was from 2 to 89 months (mean, 42 ± 25 months). One patient with recurrent angina did not need intervention of the revascularization. Six patients who acquired OPCAB and intraoperative device closure of ASD had no complications after surgery. Conclusions: Surgery for adult patients who had CHD with CAD was a safe and effective management. OPCAB with intraoperative device closure of ASD was a reasonable approach for some selective patients. (J Card Surg 2010;25:629‐632)     

Independent association of type 2 diabetes and coronary artery disease with myocardial insulin resistance

Clustering of classical cardiovascular risk factors is insufficient to account for the excess coronary artery disease (CAD) of patients with diabetes, and chronic hyperglycemia and insulin resistance (IR) are obvious culprits. Whole-body and skeletal muscle IR is characteristic of patients with type 2 diabetes, but whether it extends to the normally contracting cardiac muscle is controversial. We investigated whether type 2 diabetes is associated with myocardial IR independent of CAD in a case-control series (n = 55) of male nondiabetic and diabetic (type 2 and type 1) patients with or without angiographically documented CAD. Baseline blood flow ((15)O-water) and insulin-stimulated glucose uptake ((18)F-fluoro-deoxyglucose) during euglycemic (5.6 mmol/l), physiological hyperinsulinemia (40 mU x min(-1) x m(-2) insulin clamp) were measured by positron emission tomography in skeletal muscle and normally contracting myocardium. Skeletal muscle glucose uptake was reduced in association with both CAD and type 2 diabetes. In regions with normal baseline perfusion, insulin-mediated myocardial glucose uptake was reduced in non-CAD type 2 diabetic (0.36 +/- 0.14 micro mol x min(-1). g(-1)) and nondiabetic CAD patients (0.44 +/- 0.15 micro mol x min(- 1) x g(-1)) in comparison with healthy control subjects (0.61 +/- 0.08) or with non-CAD type 1 diabetic patients (0.80 +/- 0.13; P < 0.001 for both CAD and diabetes). Neither basal skeletal muscle nor basal myocardial blood flow differed across groups; both skeletal muscle and myocardial IR were directly related to whole-body IR. We conclude that type 2 diabetes is specifically associated with myocardial IR that is independent of and nonadditive with angiographic CAD and proportional to skeletal muscle and whole-body IR.     

Coronary revascularization in patients with coronary artery disease and chronic kidney disease

There is a remarkable lack of randomized trial data on optimal management of coronary artery disease (CAD) in patients with chronic kidney disease (CKD). In fact, patients with CKD are often excluded from randomized trials that compare different treatment strategies for CAD. Because the most common cause of death in CKD patients is cardiovascular disease, it is crucial that studies are designed to determine the best therapy for CAD in this high-risk group. This article discusses the available data on coronary revascularization outcomes in CKD patients.     

Insulin improves myocardial blood flow in patients with type 2 diabetes and coronary artery disease

Insulin infusion improves myocardial blood flow (MBF) in healthy subjects. Until now, the effect of insulin on myocardial perfusion in type 2 diabetic subjects with coronary artery disease (CAD) has been unknown. We studied the effects of insulin on MBF in ischemic regions evaluated by single-photon emission-computed tomography and coronary angiography and in nonischemic regions in 43 subjects (ages 63 +/- 7 years) with type 2 diabetes (HbA(1c) 7.1 +/- 0.9%). MBF was measured at fasting and during a euglycemic-hyperinsulinemic clamp at rest (n = 43) and during adenosine-induced (140 mug . kg(-1) . min(-1) for 7 min) hyperemia (n = 26) using positron emission tomography and (15)O-labeled water. MBF was significantly attenuated in ischemic regions as compared with in nonischemic regions (P < 0.0001) and was increased by insulin as compared with in the fasting state (P < 0.0001). At rest, insulin infusion increased MBF by 13% in ischemic regions (P = 0.043) and 22% in nonischemic regions (P = 0.003). During adenosine infusion, insulin enhanced MBF by 20% (P = 0.018) in ischemic regions and 18% (P = 0.045) in nonischemic regions. In conclusion, insulin infusion improved MBF similarly in ischemic and nonischemic regions in type 2 diabetic subjects with CAD. Consequently, in addition to its metabolic effects, insulin infusion may improve endothelial function and thus increase the threshold for ischemia and partly contribute to the beneficial effects found in clinical trials in these subjects.     

合并甲状腺功能低下病人的冠状动脉旁路移植术

目的 探讨冠心病(CAD)合并甲状腺功能低下(甲低)病人的冠状动脉旁路移植术(CABG)围术期外科处理的临床效果.方法 2002年9月至2009年6月,1347例CABG中21例(A组)合并甲低需要甲状腺激素替代治疗,男6例,女15例;平均(60.4±14.2)岁.体外循环下手术4例(包括心脏停跳手术1例),非体外循环下CABG 17例.术前均口服左旋甲状腺素,FT3、FT4、TSH、TT3、TT4明显改善后手术.同期对照20例甲状腺功能正常CABG者(B组),其中4例体外循环下CABG.观察两组术前、术中、术后甲状腺功能指标以及近端吻合时血流动力学指标.结果 围术期应用放射免疫法甲状腺激素水平检测,非体外循环下手术者,A组17例FT3术前及术中水平为[(1.39±0.36)pg/ml对(1.29±0.32)pg/ml]、B组16例为[(2.28±0.36)pg/ml对(2.19±0.34)pg/ml];体外循环下手术者,A组4例FT3术前及术中水平为[(1.53±0.51)pg/ml对(0.85±0.40)pg/ml]、B组4例为[(2.08±0.24)pg/ml对(1.96±0.26)pg/ml].A、B两组术中心排指数[(2.7±1.4)L·min-1·m-2对(2.8±1.5)L·min-1·m-2,P=0.53].A组1例重度甲低病人体外循环下心脏停跳手术后因心脏复跳困难死亡,20例生存者均为心脏不停跳方式手术者,其中17例为非体外循环手术,术后随访2～30个月均有心功能改善,射血分数(EF)由术前0.48±0.17增加至术后0.55±0.21.B组均生存.两组间术中血流动力学、手术预后、住院时间[(12.2±4.7)天对(10.1±3.9)天]、呼吸机辅助[(17.6±9.1)h对(15.1±13.7)h],差异无统计学意义.结论 冠心病合并甲低病人,术前准备充分,采用心脏不停跳手术方式较安全,非体外循环下手术对病人FT3激素水平影响较小;围术期甲状腺素治疗是关键;重度甲低病人体外循环下手术风险大.     

Surgery for coronary artery disease in patients with diabetes mellitus

The results of surgery for occlusive coronary artery disease were studied in 600 consecutive, unselected patients who underwent aortocoronary bypass grafting between Jan. 1, 1977 and Dec. 31, 1982. Forty (7%) of these patients had diabetes mellitus, requiring medication. Sixteen of the 40 patients were insulin-dependent, the remainder required oral hypoglycemic agents. The frequency of previous myocardial infarction, hypertension and peripheral vascular disease in the groups of nondiabetic and diabetic patients was 38% and 62.5%, 12% and 22.5%, and 10.5% and 25% respectively. There was no significant difference in the rate of unstable angina, triple-vessel disease, emergency surgery, left ventricular dysfunction, myocardial infarction perioperatively and hospital morbidity or mortality in the two groups. On coronary angiography, 82% of coronary arteries in diabetic patients were graded as being small or moderate in size (less than 2 mm in diameter); at operation, 62% of these arteries were found to be 2 mm or more in diameter. At a mean follow-up of 3.9 years and 3.7 years in the nondiabetic and diabetic patients respectively (range from 1 to 6 years), no significant difference was noted with regard to relief of symptoms or survival in the two groups. It is concluded that diabetic patients with coronary artery disease can be offered bypass surgery with good short-term and medium-term results.     

Vascular calcifications on screening mammography identify women with increased risk of coronary artery disease and diabetes

BACKGROUND: Mammographic breast arterial calcifications (BAC) have been reported in women with diabetes and coronary artery disease (CAD). This prospective study further investigates the clinical significance of BAC, CAD, and diabetes. METHODS: Women undergoing screening mammography were prospectively evaluated for mammographic BAC. The association among BAC, CAD, and diabetes was statistically evaluated. RESULTS: Of 1,000 consecutive women undergoing screening mammography, 181 had a history of CAD and/or diabetes. Of those women without diabetes or heart disease, 86 of 819 (10.5%) had BAC. One hundred forty women had diabetes, of whom 57 (40.7%) had BAC, and 72 women had CAD, of whom 36 (50%) had BAC. The association among BAC, CAD, and diabetes was highly significant (P <.0001, 95% confidence interval [CI]). The odds ratio of having diabetes or CAD with BAC is 4.3 and 3.6 times greater than the odds of having these diseases without BAC. COMMENTS: This large prospective study indicated a significant association between BAC identified on screening mammography and a personal history of CAD and diabetes, indicating that screening mammography may identify women at increased risk for these diseases.     

Relationship of traditional and nontraditional cardiovascular risk factors to coronary artery calcium in type 2 diabetes

We evaluated correlates of coronary atherosclerosis, measured by coronary artery calcium, in a racially diverse group of male and female subjects with type 2 diabetes. Age, systolic blood pressure, sex, and race/ethnicity were significant determinants of coronary artery calcium. Among lipoproteins, cholesterol level contained in a particle excluded from direct measures of LDL and HDL cholesterol (designated triglyceride-rich lipoprotein cholesterol) was most strongly linked to coronary artery calcium. Neither inflammatory markers nor metabolic factors correlated with coronary artery calcium in models adjusted for age and sex, but measures of adipose distribution did. Waist-to-hip ratio and the ratio of visceral to total abdominal tissue were positively associated with coronary artery calcium. In fully adjusted multivariate models, the relationship of adiposity measures to coronary artery calcium was no longer significant after inclusion of apolipoprotein B or triglyceride-rich lipoprotein cholesterol. Traditional risk factors and race/ethnicity remain important correlates of coronary artery calcium in a cohort at elevated risk of cardiovascular disease because of type 2 diabetes. Adiposity measures are significantly associated with coronary artery calcium score, but their importance may be largely explained by apolipoprotein B or triglyceride-rich lipoprotein cholesterol.     

Prevalence of asymptomatic coronary artery disease in men with vasculogenic erectile dysfunction: a prospective angiographic study

OBJECTIVES: Erectile dysfunction (ED) shares common risk factors with coronary artery disease (CAD). It has been suggested that ED may be considered a clinical manifestation of a generalized vascular disease affecting also the penile arteries. The aim of this prospective study was to evaluate angiographically the incidence of asymptomatic CAD in men with ED of vascular origin. METHODS: Fifty consecutive asymptomatic men, aged 41-74 years, with non-psychogenic and non-hormonal ED were comprehensively evaluated using medical history and examination, exercise treadmill test and stress echocardiography. Patients who had positive one or both of the two non-invasive procedures were referred for coronary arteriography in order to document CAD and evaluate the severity of the disease. RESULTS: The mean time interval between the onset of ED and cardiological assessment was 25 months (range 1-66). Smoking (32 patients/64%), hypertension (31 patients/62%) and hyperlipidemia (26 patients/52%) were the most common risk factors. Moreover, 35 men (70%) had two or more risk factors. Twelve patients (24%) with ED had positive one or both of the two non-invasive procedures and one patient presented with acute myocardial infarction before he completed the non-invasive investigation. Coronary arteriography performed in ten patients (in nine with positive one or both of the two non-invasive procedures [while the other three refused], and in the patient with acute myocardial infarction) demonstrated that one patient had three-vessel disease, two patients had two-vessel disease and six patients had single-vessel disease. CONCLUSIONS: A considerable proportion (9/47 or 19%) of patients with ED of vascular origin has angiographically documented silent CAD. These findings support the strategy that patients with ED should undergo further cardiovascular evaluation.