Risk Assessment of Major Adverse Cardiovascular and Cerebrovascular Events and Bleeding for Acute Myocardial Infarction With or Without Active Tuberculosis

PurposeThe underlying ischemic and bleeding risks of acute myocardial infarction (AMI) with active tuberculosis (TB) are unknown. The goal of this study was to explore the ischemic and bleeding risks, as well as treatment strategies during hospitalization, in patients with AMI with or without active TB.MethodsPatients were recruited from a tuberculosis hospital from 2014 to 2021. The primary outcomes were major cardiovascular and cerebrovascular events (MACE) and Bleeding Academic Research Consortium (BARC)-defined type 3 or 5 bleeding. Multivariate logistic regression and propensity score matching were performed for risk adjustment. Subgroups were defined according to AMI with active pulmonary TB and AMI with active TB undergoing percutaneous coronary intervention (PCI).FindingsA total of 242 patients were enrolled. Compared with AMI without active TB, AMI with active TB had a higher risk of MACE and BARC type 3 or 5 bleeding (P < 0.001 and P = 0.002, respectively). Multivariate logistic regression analysis showed that, compared with AMI without active TB, the odds ratio (OR) was 6.513 (95% CI, 2.195–19.331) for MACE in patients with AMI with active TB, and the OR was 16.074 (95% CI 3.337–77.436) for BARC type 3 or 5 bleeding in patients with AMI with active TB. After propensity score matching, AMI with active TB tended to increase the risk of MACE, although not statistically significantly (P = 0.189), and increased BARC type 3 or 5 bleeding (P < 0.001), compared with AMI without active TB. Results of subgroup analyses showed that active TB had outcomes consistent with those of the total cohort. AMI patients with active pulmonary TB who underwent PCI had a lower risk of MACE without an increase in the risk of bleeding compared with those not undergoing PCI.ImplicationsPatients with AMI with active TB have a higher risk of MACE (or severe MACE) and bleeding than patients with AMI without active TB. However, AMI patients with active TB are still advised to undergo PCI for a high net clinical benefit.     

Severe Hypoglycemia,Cardiac Structure and Function,and Risk of Cardiovascular Events Among Older Adults With Diabetes

OBJECTIVETo assess the association of severe hypoglycemia measured at baseline with cardiovascular disease (CVD) among community-dwelling older individuals with diabetes, a group particularly susceptible to hypoglycemia.RESEARCH DESIGN AND METHODSWe included older adults with diabetes from the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5 (2011–2013, baseline). Severe hypoglycemia at baseline was defined with use of first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls. We examined cross-sectional associations of severe hypoglycemia with echocardiographic indices of cardiac structure-function. We prospectively evaluated the risks of incident or recurrent CVD (coronary heart disease, stroke, or heart failure) and all-cause mortality, from baseline to 31 December 2018, using negative binomial and Cox regression models.RESULTSAmong 2,193 participants (mean [SD] age 76 [5] years, 57% female, 32% Blacks), 79 had a history of severe hypoglycemia at baseline. Severe hypoglycemia was associated with a lower left ventricular (LV) ejection fraction (adjusted β-coefficient −3.66% [95% CI −5.54, −1.78]), higher LV end diastolic volume (14.80 mL [95% CI 8.77, 20.84]), higher E-to-A ratio (0.11 [95% CI 0.03, 0.18]), and higher septal E/e′ (2.48 [95% CI 1.13, 3.82]). In adjusted models, severe hypoglycemia was associated with incident or recurrent CVD (incidence rate ratio 2.19 (95% CI 1.24, 3.88]) and all-cause mortality (hazard ratio 1.71 [95% CI 1.10, 2.67]) among those without prevalent CVD.CONCLUSIONSOur findings suggest that a history of severe hypoglycemia is associated with alterations in cardiac function and is an important marker of future cardiovascular risk in older adults.     

Early Menopause and Cardiovascular Disease Risk in Women With or Without Type 2 Diabetes: A Pooled Analysis of 9,374 Postmenopausal Women

OBJECTIVEEarly menopause may be associated with higher cardiovascular disease (CVD) risk. Type 2 diabetes mellitus (T2DM), coupled with early menopause, may result in even greater CVD risk in women. We examined CVD risk in women with early compared with normal-age menopause, with and without T2DM overall, and by race/ethnicity.RESEARCH DESIGN AND METHODSWe pooled data from the Atherosclerosis Risk in Communities study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. We included women with data on menopausal status, menopausal age, and T2DM, excluding pre- or perimenopausal women and those with prevalent CVD. Outcomes included incident coronary heart disease (CHD), stroke, heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD) (CHD or stroke). We estimated the risk associated with early (<45 years) compared with normal-age menopause using Cox proportional hazards models. Covariates included age, race/ethnicity, education, BMI, blood pressure, cholesterol, smoking, alcohol consumption, antihypertensive medication, lipid-lowering medication, hormone therapy use, and pregnancy history.RESULTSWe included 9,374 postmenopausal women for a median follow-up of 15 years. We observed 1,068 CHD, 659 stroke, 1,412 HF, and 1,567 ASCVD events. T2DM significantly modified the effect of early menopause on CVD risk. Adjusted hazard ratios for early menopause and the outcomes were greater in women with T2DM versus those without (CHD 1.15 [95% CI 1.00, 1.33] vs. 1.09 [1.03, 1.15]; stroke 1.21 [1.04, 1.40] vs. 1.10 [1.04, 1.16]; ASCVD 1.29 [1.09, 1.51] vs. 1.10 [1.04, 1.17]; HF 1.18 [1.00, 1.39] vs. 1.09 [1.03, 1.16]). The modifying effect of T2DM on the association between early menopause and ASCVD was only statistically significant in Black compared with White women.CONCLUSIONSEarly menopause was associated with an increased risk for CVD in postmenopausal women. T2DM may further augment the risk, particularly in Black women.     

Arterial Stiffness Is Associated With Cardiovascular,Renal, Retinal,and Autonomic Disease in Type 1 Diabetes

OBJECTIVE

In patients with type 1 diabetes, we investigated the association between arterial stiffness and diabetes complications.

RESEARCH DESIGN AND METHODS

This was a cross-sectional study including 676 Caucasian patients with type 1 diabetes (374 [55%] men, aged 54 ± 13 years [mean ± SD]) and 51 nondiabetic controls (28 [55%] men, aged 47 ± 13 years). Aortic pulse wave velocity (PWV) was measured with SphygmoCor (AtCor Medical, Sydney, Australia) for 635 patients and all 51 controls.

RESULTS

PWVs (mean ± SD) in patients and controls were 10.4 ± 3.4 and 7.6 ± 1.9 m/s, respectively (P < 0.001). After multivariate adjustment, PWV correlated with age, diabetes duration, urinary albumin excretion rate, heart rate, and blood pressure (P < 0.05 for all). ANCOVA was used for comparisons between groups and adjusted for gender, age, estimated glomerular filtration rate, heart rate, HbA_1c, and 24-h mean arterial pressure. PWVs in normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 9.5 ± 3.2, 11.0 ± 3.6, and 11.4 ± 3.0 m/s, respectively (adjusted P < 0.001). PWV in patients with previous cardiovascular disease, versus patients without, was 12.1 ± 3.5 vs. 10.0 ± 3.2 m/s, respectively (adjusted P < 0.001). PWVs in patients with high (≥140/90 mmHg) versus intermediate (130–40/80–89 mmHg) and low (<130/80 mmHg) blood pressure were 11.8 ± 3.6, 10.0 ± 3.0, and 9.8 ± 3.3 m/s, respectively (adjusted P < 0.001). Furthermore, PWV increased with increasing degree of retinopathy: 8.0 ± 2.5 m/s (nil), 10.0 ± 2.8 m/s (simplex), 12.1 ± 3.5 m/s (proliferative), and 12.7 ± 2.4 m/s (blind), respectively (adjusted P < 0.001). Finally, PWV increased with abnormal heart rate variability: 11.5 ± 3.3 m/s vs. 10.1 ± 3.1 m/s (borderline) and 8.1 ± 2.1 m/s (normal) (adjusted P = 0.027).

CONCLUSIONS

Arterial stiffness increased with presence and duration of type 1 diabetes. Furthermore, PWV increased with all the investigated diabetes complications (cardiovascular, renal, retinal, and autonomic disease) independently of other risk factors.Arterial stiffness predicts cardiovascular disease (CVD) events in the general population (1), in hypertension (2,3), and in diabetes (4,5). A recent meta-analysis by Vlachopoulos et al. (6) showed pulse wave velocity (PWV) to predict both CVD and all-cause mortality. The gold standard for measurement of arterial stiffness is aortic PWV measurements (7,8), which have shown to be reproducible in the general population (9) and in patients with chronic kidney disease (10).In hypertension, PWV is a marker of subclinical organ damage. Recent studies have shown PWV to be predictive of future changes in systolic blood pressure (SBP) development of hypertension (11) to potentially improve CVD risk scoring (12,13), and also to be higher among patients less responsive to antihypertensive medication (AHT) (14).Furthermore, in patients with end-stage renal disease, elevated PWV is an independent predictor of all-cause mortality (15), and lowering PWV by AHT reduces the mortality independently of the blood pressure (BP) reduction (16).In type 1 diabetes, PWV has been shown to be associated with cerebral microvascular disease, cardiac (17) and renal function (18), and in type 2 diabetes with microalbuminuria (19). These associations are suggestive of PWV being related to vascular dysfunction (20) and large artery alterations, thereby possibly engaging in the development of kidney impairment (21). Arterial stiffness also is associated with autonomic neuropathy in type 1 diabetes (22,23) and retinopathy in type 2 diabetes (24), further illustrating the association between arterial stiffness and microvascular disease.The current study is the first in a relatively large and diverse group of patients with type 1 diabetes to investigate the association between PWV and a range of diabetes complications, including albuminuria, CVD, elevated BP, retinopathy, and autonomic neuropathy.     

高校教师人群体脂分布对血脂、血糖及血压水平的影响

[目的]探讨高校教师人群体脂分布及对血脂、血糖及血压水平的影响。[方法]对南京农业大学157名高校教师测量体质量指数（BMI）,腰臀比（WHR）、收缩压（SBP）、舒张压（DBP）、血清总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、和空腹血糖（FBG）,并进行统计学分析比较。[结果]不同年龄分组BMI、WHR、TC、LDL-C、DBP均以45～59岁年龄层最高。FBG、SBP随年龄升高而升高,HDL-C、HDL-C/TC则随年龄升高而降低。调整年龄后,男性 TC、TG、FBG ,SBP ,女性DBP随WHR水平升高而升高。[结论]腹型肥胖是影响高校教师人群血脂、血糖及血压水平的因素,且存在男女差别。     

Androgens,Bilateral Oophorectomy,and Cardiovascular Disease Mortality in Postmenopausal Women With and Without Diabetes: The Study of Osteoporotic Fractures

OBJECTIVE

Diabetes elevates cardiovascular disease (CVD) risk more markedly in women than in men. Because the high risk of CVD among women with type 2 diabetes (DM2) may be partly due to increased ovarian androgen production, we investigated whether a history of bilateral salpingo oophorectomy (BSO) is inversely associated with CVD mortality among women with DM2.

RESEARCH DESIGN AND METHODS

Data were obtained from 7,977 women (a random subset of 564 had measurements of sex-steroid hormones) enrolled in the Study of Osteoporotic Fractures (SOF), a community-based, multicenter study that monitored women aged ≥65 years for a mean of 15.1 years. Adjusted hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression.

RESULTS

The average age at baseline was 71.5 years, with 6.3% and 18% of participants reporting a history of diabetes or BSO, respectively. In the subset of the SOF cohort with sex-steroid hormone measurements, those with DM2 had 43.6% significantly higher levels of free testosterone that were partly explained by age and adiposity, whereas total and free testosterone levels were lower in women with BSO than in those with intact ovaries. CVD mortality was elevated in women with DM2 without BSO (HR 1.95, 95% CI 1.62–2.35) as well as in women with DM2 and BSO (HR 2.56, 95% CI 1.79–3.65; P = 0.190 for interaction). Overall, BSO was not associated with CVD mortality (HR 1.05, 95% CI 0.89–1.23).

CONCLUSIONS

The association of diabetes with CVD was not reduced by BSO, suggesting that ovarian hyperandrogenemia may not be a primary mechanism to explain the high risk for CVD among women with DM2.     

Impact of Blood Lipids on 10-Year Cardiovascular Risk in Individuals Without Dyslipidemia and With Low Risk Factor Burden

ObjectiveTo determine the association of plasma lipids with the prevalence of subclinical atherosclerosis and 10-year risk of incident cardiovascular (CV) events among healthy individuals without dyslipidemia and with low risk factor burden.Patients and MethodsThe analysis (June 24, 2020, through June 12, 2021) included 1204 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) study who were current nonsmokers and did not have CV disease, hypertension (blood pressure ≥130/80 mm Hg or antihypertensive use), diabetes (fasting glucose ≥126 mg/dL or glucose-lowering medication use), and dyslipidemia (low-density-lipoprotein-cholesterol [LDL-C] ≥160 mg/dL, high-density-lipoprotein-cholesterol [HDL-C] <40 mg/dL, total cholesterol [TC] ≥240 mg/dL, triglycerides [TGs] ≥150 mg/dL, or lipid-lowering medication use) at baseline. Associations of lipids with baseline atherosclerosis (presence of carotid plaque and/or coronary calcification) and incident CV events over 10 years were examined using multivariable relative risk regression and Cox regression, respectively.ResultsAt baseline, participants’ median age was 54 (IQR, 49 to 62) years, and 10-year CV risk was 2.7% (IQR, 1.0% to 6.6%); 43.4% had subclinical atherosclerosis. A 1-SD higher LDL-C (23.4 mg/dL), TC (24.7 mg/dL), non–HDL-C (25.3 mg/dL), TC/HDL-C (0.75), and LDL-C/HDL-C (0.66) was associated with a higher prevalence of atherosclerosis of between 6% and 9% (P<.05). For every 1-SD higher LDL-C, non–HDL-C, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C (0.49), the 10-year incidence of CV events was significantly increased by 40%, 44%, 51%, 49%, and 39%, respectively. For every 1-SD lower HDL-C (13.5 mg/dL), CV risk was increased by 37%. Triglycerides had no association with either outcome.ConclusionExcept for TGs, all lipid variables were associated with atherosclerosis and future risk of CV disease among persons without dyslipidemia and with low risk factor burden.     

Smoking Is Associated With Reduced Risk of Autoimmune Diabetes in Adults Contrasting With Increased Risk in Overweight Men With Type 2 Diabetes: A 22-year follow-up of the HUNT study

OBJECTIVE

To investigate the association between smoking habits and risk of autoimmune diabetes in adults and of type 2 diabetes.

RESEARCH DESIGN AND METHODS

We used data from the three surveys of the Nord-Trøndelag Health Study, spanning 1984–2008 and including a cohort of 90,819 Norwegian men (48%) and women (52%) aged ≥20 years. Incident cases of diabetes were identified by questionnaire and classified as type 2 diabetes (n = 1,860) and autoimmune diabetes (n = 140) based on antibodies to glutamic decarboxylase (GADA) and age at onset of diabetes. Hazard ratios (HRs) adjusted for confounders were estimated by Cox proportional hazards regression models.

RESULTS

The risk of autoimmune diabetes was reduced by 48% (HR 0.52 [95% CI 0.30–0.89]) in current smokers and 58% in heavy smokers (0.42 [0.18–0.98]). The reduced risk was positively associated with number of pack-years. Heavy smoking was associated with lower levels of GADA (P = 0.001) and higher levels of C-peptide (964 vs. 886 pmol/L; P = 0.03). In contrast, smoking was associated with an increased risk of type 2 diabetes, restricted to overweight men (1.33 [1.10–1.61]). Attributable proportion due to an interaction between overweight and heavy smoking was estimated to 0.40 (95% CI 0.23–0.57).

CONCLUSIONS

In this epidemiological study, smoking is associated with a reduced risk of autoimmune diabetes, possibly linked to an inhibitory effect on the autoimmune process. An increased risk of type 2 diabetes was restricted to overweight men.Data on the influence of smoking on autoimmune diabetes are limited. A protective effect seems plausible because an anti-inflammatory effect of nicotine has been demonstrated both in vitro (1) and in vivo (2). Also, an inhibitory effect of nicotine on autoimmune diabetes has been documented in one animal study (3). In a previous study based on prospective data from the Norwegian Nord-Trøndelag Health Study (HUNT) 1984–1997, we found a reduced risk of latent autoimmune diabetes in adults (LADA) in smokers (4). Confirmatory and extended evidence for such an effect is, however, desirable.In contrast, smoking, in particular heavy smoking, is clearly associated with an increased risk of type 2 diabetes (5). The increased risk has been attributed to impaired insulin sensitivity (6), increased systematic inflammation (7), greater accumulation of abdominal adipose tissue (8), and/or adverse effects on pancreatic tissue and β-cell function (9). Overweight may modify the influence of smoking on type 2 diabetes; in one Japanese study, the association between smoking and type 2 diabetes was limited to overweight individuals (10), and findings from a Finnish study suggest that smoking is more detrimental in individuals with high BMI (11). Further studies on a possible interaction are, however, needed.The aim of this study was to extend our previous analyses of smoking in autoimmune diabetes in adults with regard to cases and follow-up time and also to include in-depth analysis of the established association of smoking with type 2 diabetes.     

Maternal Family History of Diabetes Is Associated With a Reduced Risk of Cardiovascular Disease in Women With Type 2 Diabetes: The Fremantle Diabetes Study

OBJECTIVE

To investigate whether parental family history of diabetes influences cardiovascular outcomes in type 2 diabetes.

RESEARCH DESIGN AND METHODS

We studied 1,294 type 2 diabetic patients (mean age 64.1 years, 51.2% female) recruited to a community-based cohort study from 1993 to 1996 and followed until mid-2006. A data linkage system assessed all-cause and cardiac mortality, incident myocardial infarction, and stroke. Cox proportional hazards modeling was used to determine the influence of maternal or paternal family history on these outcomes.

RESULTS

A maternal family history of diabetes was reported by 20.4% of the cohort, 8.3% reported paternal family history, and 2.0% reported both parents affected. Maternal and paternal family history was associated with earlier age of diabetes onset, and maternal family history was associated with worse glycemic control. For all patients, maternal family history was significantly associated with reduced risk of all-cause mortality and cardiac mortality. When analyzed by sex, maternal family history had no effect on male patients, whereas female patients with diabetic mothers had significantly reduced hazard ratios for death from all causes (0.63 [95% CI 0.41–0.96]; P = 0.033), for death from cardiac causes (0.32 [0.14–0.72]; P = 0.006), and for first myocardial infarction (0.45 [0.26–0.76]; P = 0.003). Paternal family history status was not associated with these outcomes.

CONCLUSIONS

A maternal family history of diabetes confers relative protection against cardiovascular disease in female patients but not in male patients with type 2 diabetes. Paternal family history is associated with risks equivalent to those without a family history of diabetes. Some of the clinical heterogeneity of type 2 diabetes is related to maternal transmission effects with differential impact on male and female patients.The complex etiology of type 2 diabetes involves both genetic components and environmental exposures. In type 2 diabetes, there is a well documented association between a family history of the disease and its development (1,2). Maternal and paternal family histories of diabetes are both associated with an earlier age of onset (2–4), and this effect is more marked when multiple family members are affected (5). In addition, intrauterine exposure to diabetes increases the risk of diabetes in offspring (6), which may help explain the reported excess maternal transmission (7,8).Patients with familial diabetes have relatively poor glycemic control, but few other clinical differences have been reported (4,5,9,10). An early age of onset and poor glycemic control would both be expected to have a negative impact on the development of chronic complications, but no such longitudinal data have been published. In the present study, we examined relationships among parental diabetes and important clinical outcomes in type 2 diabetes, including incident coronary heart disease (CHD) and all-cause and cardiac mortality in a large community-based sample of patients with type 2 diabetes. We hypothesized that familial diabetes would indicate worse clinical outcomes. We investigated potential relationships in male and female patients separately, given the known differences in CHD incidence between men and women with diabetes (11).     

Early-Adulthood Cardiovascular Disease Risk Factor Profiles Among Individuals With and Without Diabetes in the Framingham Heart Study

OBJECTIVE

Many studies of diabetes have examined risk factors at the time of diabetes diagnosis instead of considering the lifetime burden of adverse risk factor levels. We examined the 30-year cardiovascular disease (CVD) risk factor burden that participants have up to the time of diabetes diagnosis.

RESEARCH DESIGN AND METHODS

Among participants free of CVD, incident diabetes cases (fasting plasma glucose ≥126 mg/dL or treatment) occurring at examinations 2 through 8 (1979–2008) of the Framingham Heart Study Offspring cohort were age- and sex-matched 1:2 to controls. CVD risk factors (hypertension, high LDL cholesterol, low HDL cholesterol, high triglycerides, obesity) were measured at the time of diabetes diagnosis and at time points 10, 20, and 30 years prior. Conditional logistic regression was used to compare risk factor levels at each time point between diabetes cases and controls.

RESULTS

We identified 525 participants with new-onset diabetes who were matched to 1,049 controls (mean age, 60 years; 40% women). Compared with those without diabetes, individuals who eventually developed diabetes had higher levels of hypertension (odds ratio [OR], 2.2; P = 0.003), high LDL (OR, 1.5; P = 0.04), low HDL (OR, 2.1; P = 0.0001), high triglycerides (OR, 1.7; P = 0.04), and obesity (OR, 3.3; P < 0.0001) at time points 30 years before diabetes diagnosis. After further adjustment for BMI, the ORs for hypertension (OR, 1.9; P = 0.02) and low HDL (OR, 1.7; P = 0.01) remained statistically significant.

CONCLUSIONS

CVD risk factors are increased up to 30 years before diagnosis of diabetes. These findings highlight the importance of a life course approach to CVD risk factor identification among individuals at risk for diabetes.Many studies of diabetes have focused on cardiovascular disease (CVD) risk factors at the time of diabetes diagnosis. However, it is likely that CVD risk factors that accompany diabetes, including obesity, hypertension, and dyslipidemia, are increased decades before the clinical onset of diabetes. Two previous studies have suggested that individuals who develop diabetes may have increased CVD risk factor burden up to 15 years before their diabetes diagnosis, relative to those who do not have development of diabetes (1,2) However, one limitation of these studies is that 15 years before diabetes diagnosis may not be a long enough time range to capture the early middle-age period when risk factor intervention might be more feasible.A better understanding of the life-long risk factor burden that participants bear before the time of diabetes diagnosis can enable us to identify those at greatest risk for ultimate development of CVD. Thus, the objective of our study was to examine CVD risk factor burden during the time period of up to 30 years before diabetes diagnosis among individuals who did and did not develop diabetes.     

Central Pulse Pressure and Its Hemodynamic Determinants in Middle-Aged Adults With Impaired Fasting Glucose and Diabetes: The Asklepios study

OBJECTIVE

Pulse pressure (PP), a strong predictor of cardiovascular events in type 2 diabetes, is a composite measure affected by several hemodynamic factors. Little is known about the hemodynamic determinants of central PP in type 2 diabetes or whether abnormalities in central pulsatile hemodynamics are already present in individuals with impaired fasting glucose (IFG). In a population-based study, we aimed to compare central PP and its hemodynamic determinants among adults with normal fasting glucose (n = 1654), IFG (n = 240), and type 2 diabetes (n = 33).

RESEARCH DESIGN AND METHODS

We measured carotid pressure, left ventricular outflow, aortic root diameter, carotid artery flow, and distension in order to measure various structural and hemodynamic arterial parameters.

RESULTS

IFG was associated with a greater mean arterial pressure (MAP) but was not associated with intrinsic aortic stiffening or abnormal aortic pulsatile indices after adjustment for MAP. After adjustment for age, sex, and MAP, type 2 diabetes was associated with a higher aortic root characteristic impedance (Zc), aortic root elastance-thickness product (Eh), and aortic root pulse wave velocity (but not aortic root diameter), a greater carotid-femoral pulse wave velocity, and lower total arterial compliance and wave reflection magnitude. Carotid size, Zc, distensibility, or Eh did not significantly differ between the groups.

CONCLUSIONS

Type 2 diabetes, but not IFG, is associated with greater large artery stiffness, without abnormalities in aortic root diameter or carotid stiffness. Subjects with type 2 diabetes demonstrate a decreased reflection magnitude, which may indicate an increased penetration of pulsatile energy to distal vascular beds.Cardiovascular disease is a leading cause of death in adults with type 2 diabetes. Pulse pressure (PP) is a strong predictor of cardiovascular events (1–3) and independently accounts for an important proportion of such events in patients with type 2 diabetes (3). Increased PP has also been associated with microalbuminuria in type 2 diabetes (1), consistent with a role for pressure pulsatility in microvascular target organ damage, as suggested by hemodynamic principles (4,5). Whether nondiabetic subjects with impaired fasting glucose (IFG) demonstrate pulsatile hemodynamic abnormalities is unknown. IFG is far more prevalent than type 2 diabetes, is associated with an increased risk of cardiovascular mortality, and contributes to a large number of cardiovascular deaths in the general population (6). A small study demonstrated that subjects with IFG demonstrated greater aortic PP measured in the catheterization laboratory than those with normal fasting glucose (FG) (7), but it is currently unclear whether an elevated PP (or abnormalities in its hemodynamic determinants) occur in association with IFG in unselected samples from the general population.PP is a composite hemodynamic measure affected by several factors. Early in systole, the aortic root offers an impedance to blood flow that results in an increase in pulsatile pressure. The aortic property that determines the amount of pressure increase for any given left ventricular flow output during early systole is the proximal aortic characteristic impedance (Zc). Provided a given proximal aortic relative geometry (wall thickness/lumen ratio), aortic Zc is linearly related to the inverse of aortic luminal cross-sectional area and to the square root of the elastic modulus (stiffness) of the proximal aortic wall material. Aortic PP is also affected by wave reflections arising from the periphery, which generally arrive to the aorta in midsystole and augment mid- to late systolic pressure. The magnitude of wave reflections is influenced by the impedance mismatch between the central and peripheral arteries, whereas for any given distance to the reflection sites, the timing of arrival of wave reflections to the proximal aorta is influenced by aortic pulse wave velocity (PWV). Aortic PWV, in turn, is affected by wall stiffness and, provided any given relative geometry (lumen diameter to wall thickness ratio), is not affected by absolute aortic dimension. In addition to the factors mentioned above, PP is influenced by the total compliance of the arterial tree (TAC), which is influenced by arterial size, geometry and wall stiffness. Given the multiple determinants of PP, it follows that multiple potential abnormalities in arterial structure and hemodynamic function may lead to an increased PP in type 2 diabetes. Given the impact of PP on cardiovascular risk in type 2 diabetes, a better understanding of such determinants is important. A previous study demonstrated a greater proximal aortic Zc among 17 patients with type 1 diabetes mellitus compared with nondiabetic control subjects (8), but to our knowledge, the hemodynamic determinants of PP in type 2 diabetes have not been systematically investigated. Clearly, there is a need to: 1) understand the determinants of increased PP in type 2 diabetes and its potential impact on the pulsatility transmission to target organs and 2) assess whether abnormalities in pulsatile hemodynamic function are already present in subjects with IFG.In this study, we aimed to comprehensively assess and compare parameters of arterial structure and pulsatile hemodynamic function among middle-aged adults with type 2 diabetes, IFG, and normal FG in the general population.     

Sustained Benefit of Continuous Glucose Monitoring on A1C, Glucose Profiles, and Hypoglycemia in Adults With Type 1 Diabetes

OBJECTIVE

To evaluate long-term effects of continuous glucose monitoring (CGM) in intensively treated adults with type 1 diabetes.

RESEARCH DESIGN AND METHODS

We studied 83 of 86 individuals ≥25 years of age with type 1 diabetes who used CGM as part of a 6-month randomized clinical trial in a subsequent 6-month extension study.

RESULTS

After 12 months, median CGM use was 6.8 days per week. Mean change in A1C level from baseline to 12 months was −0.4 ± 0.6% (P < 0.001) in subjects with baseline A1C ≥7.0%. A1C remained stable at 6.4% in those with baseline A1C <7.0%. The incidence rate of severe hypoglycemia was 21.8 and 7.1 events per 100 person-years in the first and last 6 months, respectively. Time per day with glucose levels in the range of 71–180 mg/dl increased significantly (P = 0.02) from baseline to 12 months.

CONCLUSIONS

In intensively treated adults with type 1 diabetes, CGM use and benefit can be sustained for 12 months.In a 6-month randomized trial of intensively treated individuals with type 1 diabetes and baseline A1C ≥7.0%, adults ≥25 years of age benefited from use of continuous glucose monitoring (CGM) compared with adults using conventional blood glucose monitoring (1). In a contemporaneous parallel study of individuals with type 1 diabetes who had A1C levels <7.0%, those in the CGM group had a reduction in biochemical hypoglycemia compared with those in the control group while maintaining A1C levels in the target range (2). This report describes the 12-month follow-up of adult subjects in the two randomized trials'' CGM groups.     

Legacy Effect of Intensive Blood Glucose Control on Cardiovascular Outcomes in Patients With Type 2 Diabetes and Very High Risk or Secondary Prevention of Cardiovascular Disease: A Meta-analysis of Randomized Controlled Trials

Purpose

We performed a meta-analysis to investigate the legacy effect of >5 years of intensive blood glucose lowering on cardiovascular outcomes in patients with type 2 diabetes and very high risk or secondary prevention of cardiovascular disease (CVD).

Sex Differences in Coronary Artery Calcium and Mortality From Coronary Heart Disease,Cardiovascular Disease,and All Causes in Adults With Diabetes: The Coronary Calcium Consortium

OBJECTIVEWhile diabetes has been previously noted to be a stronger risk factor for cardiovascular disease (CVD) in women compared with men, whether this is still the case is not clear. Coronary artery calcium (CAC) predicts coronary heart disease (CHD) and CVD in people with diabetes; however, its sex-specific impact is less defined. We compared the relation of CAC in women versus men with diabetes for total, CVD, and CHD mortality.RESEARCH DESIGN AND METHODSWe studied adults with diabetes from a large registry of patients with CAC scanning with mortality follow-up over 11.5 years. Cox regression examined the relation of CAC with mortality end points.RESULTSAmong 4,503 adults with diabetes (32.5% women) aged 21–93 years, 61.2% of women and 80.4% of men had CAC >0. Total, CVD, and CHD mortality rates were directly related to CAC; women had higher total and CVD death rates than men when CAC >100. Age- and risk factor–adjusted hazard ratios (HRs) per log unit CAC were higher among women versus men for total mortality (1.28 vs. 1.18) (interaction P = 0.01) and CVD mortality (1.47 vs. 1.27) (interaction P = 0.04) but were similar for CHD mortality (1.48 and 1.48). For CVD mortality, HRs with CAC scores of 101–400 and >400 were 3.67 and 6.27, respectively, for women and 1.63 and 3.48, respectively, for men (interaction P = 0.04). For total mortality, HRs were 2.56 and 4.05 for women, respectively, and 1.88 and 2.66 for men, respectively (interaction P = 0.01).CONCLUSIONSCAC predicts CHD, CVD, and all-cause mortality in patients with diabetes; however, greater CAC predicts CVD and total mortality more strongly in women.     

Sex Differences in All-Cause and Cardiovascular Mortality,Hospitalization for Individuals With and Without Diabetes,and Patients With Diabetes Diagnosed Early and Late

OBJECTIVE

To compare risk of all-cause mortality, cardiovascular disease (CVD) mortality, acute myocardial infarction (AMI) mortality, stroke mortality, and hospitalizations for males and females with and without diabetes and those with diabetes diagnosed early and late.

RESEARCH DESIGN AND METHODS

We conducted a population-based retrospective cohort study including 73,783 individuals aged 25 years or older in Newfoundland and Labrador, Canada (15,152 with diabetes; 9,517 with late diagnoses).

RESULTS

Males and females with diabetes had an increased risk of all-cause mortality, CVD mortality, AMI mortality, and CVD hospitalizations compared with individuals without diabetes, and the risk was stronger in females than in males. For females, risks of all-cause mortality (hazard ratio [HR] 1.85 [95% CI 1.74–1.96]) and CVD hospitalizations (2.57 [2.24–2.94]) were significantly higher compared with their male counterparts (1.59 [1.51–1.69] and 1.92 [1.72–2.14]). Females with diabetes diagnosed late had an increased risk of CVD mortality (6.54 [4.80–8.91]) and CVD hospitalizations (5.22 [4.31–6.33]) compared with females without diabetes, and both were significantly higher compared with their male counterparts (3.44 [2.47–4.79]) and (3.33 [2.80–3.95]).

CONCLUSIONS

Females with diabetes have a greater risk of mortality than males with diabetes. CVD has a greater impact on females with diabetes than males, especially when diagnosed at a later stage. Different management strategies should be considered for males and females and those with early and late diagnoses of diabetes.Diabetes has become a health problem of increasing significance in the past two decades. The number of individuals with diabetes will reach 366 million in 2011 and will increase to 552 million by 2030 (1). In Canada, the age-standardized incidence and prevalence of diabetes have been increasing in recent years (2).A challenge with type 2 diabetes is the late diagnosis of the disease because many individuals who meet the criteria are often asymptomatic. Approximately 183 million people, or half of those who have diabetes, are unaware they have the disease (1). Furthermore, type 2 diabetes can be present for 9 to 12 years before being diagnosed and, as a result, complications are often present at the time of diagnosis (3). Insulin resistance and β-cell dysfunction are largely responsible for the development of diabetes and its related complications, and both are present very early in the natural history of diabetes (4). However, the potential does exist to prevent or at least delay the onset of type 2 diabetes because several randomized control trials have shown that both lifestyle and pharmacologic interventions in adults are effective (5–8). In addition to preventing diabetes, it is also possible to reduce diabetes-related complications through intensive blood glucose control. Results from the UK Prospective Diabetes Study (UKPDS) have shown that intensive blood glucose control reduces diabetes-related complications (6–9). Early detection of type 2 diabetes is critical because effective and active management is essential for those with newly diagnosed diabetes who have not developed complications.Cardiovascular disease (CVD) is the most common comorbidity associated with diabetes, and with 50% of those with diabetes dying of CVD it is the most common cause of death (1). Acute myocardial infarction (AMI) and stroke are other common comorbidities associated with diabetes. Individuals with diabetes have an increased risk of all-cause mortality and morbidity related to CVD, AMI, and stroke compared with individuals without diabetes (9–12). Although studies consistently have found that individuals with diabetes have a higher risk of mortality and hospitalizations compared with those without diabetes, results have been inconsistent when comparing males and females. Most studies have found that females with diabetes have a greater risk of mortality and hospitalizations than males with diabetes (9,10,12–17). Two previous meta-analyses found that diabetes is a stronger risk factor for CVD mortality in females than in males; however, studies that did not adjust for major CVD risk factors were included in these meta-analyses (18,19). A meta-analysis conducted by Kanaya et al. (20), which included studies that controlled for CVD risk factors, found that the risks associated with diabetes for coronary heart disease mortality, nonfatal myocardial infarction, and CVD were higher among females than males. However, the differences were not statistically significant.Newfoundland and Labrador has the highest age-standardized prevalence of diabetes in Canada (2), and the age-standardized mortality and hospitalization rates for CVD, AMI, and stroke are some of the highest in the country (21,22). A better understanding of mortality and hospitalizations associated with diabetes for males and females is important to support diabetes prevention and management. Therefore, the objectives of this study were to compare the risk of all-cause, CVD, AMI, and stroke mortality and hospitalizations for males and females with and without diabetes and those with early and late diagnoses of diabetes.     

Postchallenge Glucose, A1C, and Fasting Glucose as Predictors of Type 2 Diabetes and Cardiovascular Disease: A 10-year prospective cohort study

OBJECTIVE

A1C has been proposed as a new indicator for high risk of type 2 diabetes. The long-term predictive power and comparability of elevated A1C with the currently used high-risk indicators remain unclear. We assessed A1C, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) as predictors of type 2 diabetes and cardiovascular disease (CVD) at 10 years.

RESEARCH DESIGN AND METHODS

This prospective population-based study of 593 inhabitants from northern Finland, born in 1935, was conducted between 1996 and 2008. An oral glucose tolerance test (OGTT) was conducted at baseline and follow-up, and A1C was determined at baseline. Those with a history of diabetes were excluded from the study. Elevated A1C was defined as 5.7–6.4%. Incident type 2 diabetes was confirmed by two OGTTs. Cardiovascular outcome was measured as incident CVD or CVD mortality. Multivariate log-binomial regression models were used to predict diabetes, CVD, and CVD mortality at 10 years. Receiver operating characteristic curves compared predictive values of A1C, IGT, and IFG.

RESULTS

Incidence of diabetes during the follow-up was 17.1%. Two of three of the cases of newly diagnosed diabetes were predicted by a raise in ≥1 of the markers. Elevated A1C, IGT, or IFG preceded diabetes in 32.8, 40.6, and 21.9%, respectively. CVD was predicted by an intermediate and diabetic range of 2-h glucose but only by diabetic A1C levels in women.

CONCLUSIONS

A1C predicted 10-year risk of type 2 diabetes at a range of A1C 5.7–6.4% but CVD only in women at A1C ≥6.5%.Early detection of high risk for type 2 diabetes is fundamental for prevention of diabetes and associated cardiovascular complications. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are currently used for diagnosis of high-risk glucose levels below the diabetic range. The International Expert Committee proposed A1C ≥6.5% as a diagnostic tool for diabetes in 2009 (1) and in January 2010 an intermediate range of A1C 5.7–6.4% (elevated A1C) was proposed by the American Diabetes Association (ADA) to detect individuals at high risk for developing type 2 diabetes (2).To date, however, limited data exist to support the use of A1C in predicting type 2 diabetes (3–8). Importantly, the long-term predictive power of elevated A1C as defined above has not yet been investigated. Previous data on the association between A1C and incident type 2 diabetes in unselected populations have relied on self-reporting, fasting glucose measurements, and use of antidiabetes medication to determine the outcomes. An oral glucose tolerance test (OGTT) has not been used to determine the outcome (3–8).Deterioration of glucose homeostasis reflects a continuum of glycemia, some of which is reversible if detected early (9,10). Importantly, the risk of cardiovascular disease is increased already before glycemia reaches the levels of diabetes, and 2-h glucose appears to be a better predictor of cardiovascular disease (CVD) than fasting glucose (11). Recently, A1C was shown to be a better predictor of CVD than fasting glucose (12).Data directly comparing 2-h glucose and A1C as long-term predictors of new-onset cardiovascular disease are scarce, and results are controversial (13,14). Therefore, we compared A1C, 2-h glucose, and fasting glucose as predictors of type 2 diabetes, CVD, and CVD mortality during a prospective population-based study with a 10-year follow-up.     

Effects of Randomization to Intensive Glucose Control on Adverse Events,Cardiovascular Disease,and Mortality in Older Versus Younger Adults in the ACCORD Trial

OBJECTIVE

We explore the effect of randomized treatment, comparing intensive to standard glucose-lowering strategies on major cardiovascular outcomes, death, and severe adverse events in older versus younger participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

RESEARCH DESIGN AND METHODS

Participants with type 2 diabetes (n = 10,251) with a mean age of 62 years, a median duration of diabetes of 10 years, and a median A1C of 8.1% (65 mmol/mol) were randomized to treatment strategies targeting either A1C <6.0% (42 mmol/mol) or 7.0–7.9% (53–63 mmol/mol) and followed for a mean of 3.7 years. Outcomes were analyzed within subgroups defined by baseline age (<65 vs. ≥65 years).

RESULTS

Older and younger ACCORD participants achieved similar intensive-arm A1C levels and between-arm A1C differences. Within the older subgroup, similar hazards of the cardiovascular primary outcome and total mortality were observed in the two arms. While there was no intervention effect on cardiovascular mortality in the older subgroup, there was an increased risk in the intensive arm for the younger subgroup (older hazard ratio [HR] = 0.97; younger HR = 1.71; P = 0.03). Regardless of intervention arm, the older subgroup experienced higher annualized rates of severe hypoglycemia (4.45% intensive and 1.36% standard) than the younger subgroup (2.45% intensive and 0.80% standard).

CONCLUSIONS

Intensive glucose lowering increased the risk of cardiovascular disease and total mortality in younger participants, whereas it had a neutral effect in older participants. The intensive to standard relative risk of severe hypoglycemia was similar in both age subgroups, with higher absolute rates in older participants within both treatment arms.