Longitudinal blood glucose level and increased silent myocardial infarction: a pooled analysis of four cohort studies.

BACKGROUND: Fasting glucose (FG) demonstrates dynamic fluctuations over time and is associated with cardiovascular outcomes, yet current research is limited by small sample sizes and relies solely on baseline glycemic levels. Our research aims to investigate the longitudinal association between FG and silent myocardial infarction (SMI) and also delves into the nuanced aspect of dose response in a large pooled dataset of four cohort studies. METHODS: We analyzed data from 24,732 individuals from four prospective cohort studies who were free of myocardial infarction history at baseline. We calculated average FG and intra-individual FG variability (coefficient of variation), while SMI cases were identified using 12-lead ECG exams with the Minnesota codes and medical history. FG was measured for each subject during the study's follow-up period. We applied a Cox regression model with time-dependent variables to assess the association between FG and SMI with adjustment for age, gender, race, Study, smoking, longitudinal BMI, low-density lipoprotein level, blood pressure, and serum creatinine. RESULTS: The average mean age of the study population was 60.5 (sd: 10.3) years with median fasting glucose of 97.3 mg/dL at baseline. During an average of 9 years of follow-up, 357 SMI events were observed (incidence rate, 1.3 per 1000 person-years). The association between FG and SMI was linear and each 25 mg/dL increment in FG was associated with a 15% increase in the risk of SMI. This association remained significant after adjusting for the use of lipid-lowering medication, antihypertensive medication, antidiabetic medication, and insulin treatment (HR 1.08, 95% CI 1.01-1.16). Higher average FG (HR per 25 mg/dL increase: 1.17, 95% CI 1.08-1.26) and variability of FG (HR per 1 sd increase: 1.23, 95% CI 1.12-1.34) over visits were also correlated with increased SMI risk. CONCLUSIONS: Higher longitudinal FG and larger intra-individual variability in FG over time were associated in a dose-response manner with a higher SMI risk. These findings support the significance of routine cardiac screening for subjects with elevated FG, with and without diabetes.

The 4th Report of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy.

The 4th Report provides a brief review of publications focused on the electrocardiographic diagnosis of left ventricular hypertrophy published during the period of 2010 to 2016 by the members of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy. The Working Group recommended that ECG research and clinical attention be redirected from the estimation of LVM to the identification of electrical remodeling, to better understanding the sequence of events connecting electrical remodeling to outcomes. The need for a re-definition of terms and for a new paradigm is also stressed.

Prediabetes and the association with unrecognized myocardial infarction in the multi-ethnic study of atherosclerosis.

BACKGROUND: With one-quarter of initial myocardial infarctions (MI) being unrecognized MI (UMI), recognition is critical to minimize further cardiovascular risk. Diabetes mellitus is an established risk factor for UMI. If impaired fasting glucose (IFG) also increased the risk for UMI, it would represent a significant public health challenge due to the rapid worldwide increase in IFG prevalence. We compared participants with IFG to those with normal fasting glucose (NFG) to determine if IFG was associated with UMIs. METHODS: We performed cross-sectional analyses from the MESA, a population-based cohort study. There were 6,814 participants recruited during July 2000 to September 2002 from the general community at 6 field sites. After excluding those with diabetes mellitus or missing variables, 5,885 participants were included. At baseline, there were 4,955 participants with NFG and 930 participants with IFG. The main outcome was an UMI defined by the presence of pathological Q waves or minor Q waves with ST-T abnormalities on initial 12-lead electrocardiogram. Logistic regression was used to generate crude ORs and adjust for covariates. RESULTS: There was a higher prevalence of UMI in those with IFG compared with those with NFG [3.5% (n = 72) vs 1.4% (n = 30)]. After adjustment for multiple risk factors, there was a higher odds of an UMI among those with IFG compared with those with NFG [OR: 1.60 (95% CI: 1.0-2.5); P = .048]. CONCLUSIONS: Impaired fasting glucose is associated with unrecognized myocardial infarctions in a multi-ethnic population free of baseline cardiovascular disease.

Emerging risk factors as markers for carotid intima media thickness scores.

AIMS: Cardiovascular disease (CVD) remains the number one cause of mortality in the Western world. This study aims to determine which lifestyle factors are associated with mean carotid intima media thickness (IMT), a safe and reliable predictor of future CVD risk. METHODS AND RESULTS: A prospective cross-sectional analysis of 592 subjects. Measures were made of body composition, anthropometric measures, fitness, diet (measured with a 3-day food diary), laboratory results, and mean carotid IMT. Multivariate analyses show that higher mean IMT values are associated with increasing age (p < 0.0001), male gender (p = 0.0002), higher systolic blood pressure (BP; p = 0.0008), higher body mass index (BMI; p = 0.0005), and lower intake of zinc (p = 0.0001). Bivariate analyses controlling for age and gender, with and without statin use, showed that higher mean IMT scores were statistically associated with higher diastolic BP (p = 0.007), higher total cholesterol/high-density lipoprotein (HDL) ratio (p < 0.0001), higher triglyceride/HDL ratio (p = 0.0001), lower aerobic capacity measures (p = 0.0007), higher body fat percentage and waist circumference (p < 0.0001), higher fasting glucose level (p = 0.028), and lower intake of magnesium (p = 0.019), fish (p = 0.007), and fiber (p = 0.02). Other factors that were not associated with mean IMT include total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP); intake of saturated fat, potassium, calcium, sodium, or vitamin K; percentage of calories from protein, fat, or carbohydrate; measures of strength (assessed with push-up and sit-up testing); and reported exercise. CONCLUSIONS: Aerobic fitness and dietary intake of fiber, fish, magnesium, and zinc are inversely associated with carotid IMT scores. Of the traditional CVD risk factors, only systolic BP, fasting glucose, body composition, and total cholesterol/HDL ratio have a direct relationship with mean carotid IMT.

Electrocardiographic left ventricular strain pattern: everything old is new again.

Electrocardiographic left ventricular hypertrophy (LVH) has many faces with countless features. Beyond the classic measures of LVH, including QRS voltage and duration, the left ventricular (LV) strain pattern is an element whereby characteristic R-ST depression is followed by a concave ST segment that ends in an asymmetrically inverted T wave. The LV strain pattern generally appears in states of increased systemic blood pressure and must be differentiated from similar but not identical ST-T waves indicating ischemia. The LV strain pattern has been found in population studies to be associated with poor prognosis and increased risk of adverse cardiovascular outcomes. Regression of LV strain pattern parallels decline in systemic BP during clinical trials of anti-hypertensive therapies but does not indicate or serve as a surrogate for decrease in LV mass. Newer techniques in data collection and processing may allow the process of strain to be studied in more detail to determine the ways in which electrical remodeling of the left ventricle as characterized by LVH with 'repolarization abnormalities' indicates how CV risk might be managed by using LV strain pattern as an electrocardiographic biomarker.

Preventing new-onset heart failure: Intervening at stage A.

Heart failure (HF) prevention is an urgent public health need with national and global implications. Stage A HF patients do not show HF symptoms or structural heart disease but are at risk of HF development. There are no unique recommendations on detecting Stage A patients. Patients in Stage A are heterogeneous; many patients have different combinations of risk factors and, therefore, have markedly different absolute risks for HF. Comprehensive strategies to prevent HF at Stage A include intensive blood pressure lowering, adequate glycemic and lipid management, and heart-healthy behaviors (adopting Life's Essential 8). First and foremost, it is imperative to improve public awareness of HF risk factors and implement healthy lifestyle choices very early. In addition, recognize the HF risk-enhancing factors, which are nontraditional cardiovascular (CV) risk factors that identify individuals at high risk for HF (genetic susceptibility for HF, atrial fibrillation, chronic kidney disease, chronic liver disease, chronic inflammatory disease, sleep-disordered breathing, adverse pregnancy outcomes, radiation therapy, a history of cardiotoxic chemotherapy exposure, and COVID-19). Early use of biomarkers, imaging markers, and echocardiography (noninvasive measures of subclinical systolic and diastolic dysfunction) may enhance risk prediction among individuals without established CV disease and prevent chemotherapy-induced cardiomyopathy. Efforts are needed to address social determinants of HF risk for primordial HF prevention.Central illustrationPolicies developed by organizations such as the American Heart Association, American College of Cardiology, and the American Diabetes Association to reduce CV disease events must go beyond secondary prevention and encompass primordial and primary prevention.

Relation of glycemic status with unrecognized MI and the subsequent risk of mortality: The Jackson Heart Study.

Background: Almost 1/3 to 1/2 of initial myocardial infarctions (MI) may be silent or unrecognized (UMI), which forecasts future clinical events. Further, limited data exist to describe the potential risk for UMI in African-Americans. The relationship of glucose status with UMI was examined in the Jackson Heart Study: a cohort of African-American individuals. Methods and results: At baseline, there were 5,073 participants with an initial 12-lead electrocardiogram (ECG) and fasting glucose measured. Of these participants, 106(2.1%) had a UMI, and 268(4.2%) had a recognized MI. This population consisted of 3,233 (63.7%) participants with normal fasting glucose (NFG), 533 (10.5%) with IFG, and 1,039 (20.4%) with DM. Logistic regression investigated the relationship between glucose status and UMI. Cox proportional hazard models determined the significance of all-cause mortality during follow-up by MI status. The sample was 65% female with a mean age of 55.3 ± 12.9 years. Over a mean follow-up of 10.4 years, there were 795 deaths. Relative to NFG, the crude odds ratio (OR) estimates for UMI at baseline with IFG and DM were 1.00(95% CI:0.48-2.14) and 3.22(2.15-4.81), respectively. With adjustment, DM continued to be significantly associated with UMI [2.30 (1.42-3.71)]. Overall, participants with a baseline UMI had an adjusted Hazard ratio (HR) of 2.00(1.39-2.78) of death compared to no prior MI. Compared to those with no MI, those with a recognizedMI had an adjusted HR of 1.70(1.31-2.17) for mortality. Conclusions: DM is associated with UMI in African-Americans. Further, a UMI carried similar risk of death compared to those with a recognized MI.

Highlights in ASCVD Primary Prevention for 2021.

This review examines key studies published in 2021 that are related to primary prevention of atherosclerotic cardiovascular disease (ASCVD). Major randomized clinical trials (RCTs) concerning traditional risk factors or ASCVD events, meta-analyses, and key observational studies related to primary prevention of ASCVD were considered. The review includes interventions for weight loss, cardiometabolic and renal disease, blood pressure control, diet, and the occurrence of cardiovascular disease events. A few studies considered both primary and secondary prevention populations. The review is not exhaustive. We did not include studies that focused on heart failure or clinical presentations that may be difficult to classify, such as acute or chronic ischemic cardiovascular disease without myocardial infarction. Our purpose was to highlight recent research that will help the reader stay abreast of the changing field of cardiovascular prevention.

Prevention of heart failure: a scientific statement from the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group.

The increase in heart failure (HF) rates throughout the developed and developing regions of the world poses enormous challenges for caregivers, researchers, and policymakers. Therefore, prevention of this global scourge deserves high priority. Identifying and preventing the well-recognized illnesses that lead to HF, including hypertension and coronary heart disease, should be paramount among the approaches to prevent HF. Aggressive implementation of evidence-based management of risk factors for coronary heart disease should be at the core of HF prevention strategies. Questions currently in need of attention include how to identify and treat patients with asymptomatic left ventricular systolic dysfunction (Stage B HF) and how to prevent its development. The relationship of chronic kidney disease to HF and control of chronic kidney disease in prevention of HF need further investigation. Currently, we have limited understanding of the pathophysiological basis of HF in patients with preserved left ventricular systolic function and management techniques to prevent it. New developments in the field of biomarker identification have opened possibilities for the early detection of individuals at risk for developing HF (Stage A HF). Patient groups meriting special interest include the elderly, women, and ethnic/racial minorities. Future research ought to focus on obtaining a much better knowledge of genetics and HF, especially both genetic risk factors for development of HF and genetic markers as tools to guide prevention. Lastly, a national awareness campaign should be created and implemented to increase public awareness of HF and the importance of its prevention. Heightened public awareness will provide a platform for advocacy to create national research programs and healthcare policies dedicated to the prevention of HF.

Prospective assessment of the occurrence of anemia in patients with heart failure: results from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry.

BACKGROUND: Although a potentially important pathophysiologic factor in heart failure, the prevalence and predictors of anemia have not been well studied in unselected patients with heart failure. METHODS: The Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry prospectively studied the prevalence of anemia and the relationship of hemoglobin to health-related quality of life and outcomes among patients with heart failure. A random selection algorithm was used to reduce bias during enrollment of patients seen in specialty clinics or clinics of community cardiologists with experience in heart failure. In this initial report, data on prevalence and correlates of anemia were analyzed in 1,076 of the 1,082 registry patients who had clinical characteristics and hemoglobin determined by finger-stick at baseline. RESULTS: Overall (n = 1,082), the registry patients were 41% female and 73% white with a mean age (+/-SD) of 64 +/- 14 years (68 +/- 13 years in community and 57 +/- 14 years in specialty sites, P < .001). Among the 1,076 patients in the prevalence analysis, mean hemoglobin was 13.3 +/- 2.1 g/dL (median 13.2 g/dL); and anemia (defined by World Health Organization criteria) was present in 34%. Age identified patients at risk for anemia, with 40% of patients >70 years affected. CONCLUSIONS: Initial results from the STAMINA-HFP Registry suggest that anemia is a common comorbidity in unselected outpatients with heart failure. Given the strong association of anemia with adverse outcomes in heart failure, this study supports further investigation concerning the importance of anemia as a therapeutic target in this condition.

Abnormal Fasting Glucose Increases Risk of Unrecognized Myocardial Infarctions in an Elderly Cohort.

OBJECTIVES: To investigate glucose levels as a risk factor for unrecognized myocardial infarctions (UMIs). DESIGN: Cohort SETTING: Cardiovascular Health Study. PARTICIPANTS: Individuals aged 65 and older with fasting glucose measurements (N=4,355; normal fasting glucose (NFG), n = 2,041; impaired fasting glucose (IFG), n = 1,706; DM: n = 608; 40% male, 84% white, mean age 72.4 ± 5.6). MEASUREMENTS: The relationship between glucose levels and UMI was examined. Participants with prior coronary heart disease (CHD) or UMI on initial electrocardiography were excluded. Using Minnesota codes, UMI was identified according to the presence of pathological Q-waves or minor Q-waves with ST-T abnormalities. Crude and adjusted hazard ratios (HRs) were calculated. Analyses were adjusted for age, sex, body mass index (BMI), hypertension, antihypertensive and lipid-lowering medication use, total cholesterol, high-density lipoprotein cholesterol, and smoking status. RESULTS: Over a mean follow-up of 6 years, there were 459 incident UMIs (NFG, n=202; IFG, n=183; DM, n=74). Participants with IFG were slightly more likely than those with NFG to experience a UMI (hazard ratio (HR)=1.11, 95% confidence interval (CI)=0.91-1.36, p = .30), and those with DM were more likely than those with NFG to experience a UMI (HR=1.65, 95% CI=1.25-2.13, p < .001). After adjustment HR for UMI in IFG those with IFG were no more likely than those with NFG to experience a UMI (HR=1.01, 95% CI=0.82-1.24, p = .93), whereas those with DM were more likely than those with NFG to experience a UMI (HR=1.37, 95% CI=1.02-1.81, p = .03). The 2-hour oral glucose tolerance test was not statistically significantly associated with UMI. CONCLUSION: Fasting glucose status, particularly in the diabetic range, forecasted UMI during 6 years of follow-up in elderly adults. Further studies are needed to clarify the level of glucose at which risk is greater. J Am Geriatr Soc 67:43-49, 2019.

Racial/ethnic disparities in mortality related to congenital heart defects among children and adults in the United States.

BACKGROUND: Congenital heart defects (CHD) are the most common birth defect and are a major cause of childhood illness and death. Recent progress in management of persons with CHD may have decreased CHD-related mortality. METHODS: Year 2000 US death records were used to determine CHD-related mortality by age, sex, and race/ethnicity in children and adults. CHD-related mortality was defined as all deaths with any mention of CHD on the death certificate. Age-, sex-, and racial/ethnic-specific population counts were obtained from the 2000 US Census and used as denominators in mortality rates. RESULTS: In 2000 there were 5441 (.23%) CHD-related deaths and CHDs were mentioned 6121 times as the underlying or contributing cause of death. In 68.4% of CHD-related deaths, CHD was the underlying cause of death. Non-Hispanic Black males had greater risk of CHD-related death than did non-Hispanic White males (RR 1.25, 95% CI 1.08-1.45). Both Hispanic males and females had lower rates of CHD-related deaths than did non-Hispanic Whites (RR .72, 95% CI .60-.85; RR .52, 95% CI .42-.65, respectively). "Unspecified congenital malformation of the heart" was the most common cause of death overall; however, "malformation of the coronary vessels" was most often a cause of death for non-Hispanic Blacks and children aged 10-19 years. CONCLUSIONS: Racial/ethnic differences in CHD-related mortality exist in the United States. Management of CHD, access to adequate care, and misclassification in cause of death reporting on death records may explain the observed differences.

Diabetes-induced bradycardia is an intrinsic metabolic defect reversed by carnitine.

Rats with streptozotocin-induced diabetes (STZ-D) have reduced serum carnitine levels and bradycardia. Heart rates (HRs) of 24nondiabetic rats (NRs) and 24 STZ-D rats were compared. L-carnitine (C) was added to the drinking water of rats (12 STZ-D+C) to raise their serum carnitine level. The intrinsic HR for each animal was determined after parasympathetic and sympathetic blockade. The HRs of STZ-D rats (278+/-15 beats per minute) were less than those of NRs (348+/-8 beats per minute) (P<.01). STZ-D rats had low serum carnitine compared with control and STZ-D+C rats. The difference in HR of STZ-D rats and NRs continued after blockade, indicating that the bradycardia ofdiabetes is intrinsic to the heart. The metabolic milieu reflected in the rats' urinary organic acid profiles differed between the control and STZ-D rats. The HR of STZ-D+C rats (326+/-5 beats per minute) did not differ from those of NRs. Increasing either the insulin dose or the serum free carnitine reduced urinary organic acids, but normal HRs were associated only with elevated serum carnitine levels. When glucose is compromised as a myocardial energy source (diabetes mellitus), we propose that elevated levels of serum carnitine may increase myocardial fatty acid metabolism sufficiently to correct the bradycardia of STZ-D rats.

Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats.

BACKGROUND: Streptozotocin-induced diabetes (STZ-D) in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement. AIM: The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats. METHODS: Wistar rats (48) were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24) were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA) were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks. RESULTS: The heart rates for the STZ-D rats (290 +/- 19 bpm) were less than control rats (324 +/- 20 bpm) (p < 0.05). After 4 weeks of oral carnitine supplementation, the serum carnitine and heart rates of the STZ-D rats returned to normal. Dobutamine stress increased the heart rates of all study animals, but the increase in STZ-D rats (141 +/- 8 bpm) was greater than controls (79 +/- 8 bpm) (p < 0.05). The heart rates of STZ-D rats given oral carnitine, however, were no different than controls (94 +/- 9 bpm). The left ventricular mass/body weight ratio (LVM/BW) in the diabetic animals (2.7 +/- 0.5) was greater than control animals (2.2 +/- 0.3) (p < 0.05) after 18 weeks of diabetes. In contrast, the LVM/BW (2.3 +/- .2) of the STZ-D animals receiving supplemental carnitine was the same as the control animals at 18 weeks. CONCLUSION: Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.

Cardiac tamponade complicating trimodal therapy for malignant mesothelioma.

Trimodal therapy, which includes extrapleural pneumonectomy as the cytoreductive procedure followed by combination chemoradiotherapy, is becoming the standard of care in the treatment of malignant mesothelioma. We report here a case of hypotension secondary to tension hydrothorax in which echocardiography and hemodynamic monitoring demonstrated evidence of tamponade physiology. Thoracentesis was lifesaving.