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Aims To assess the current state of statin use, factors associated with non-use, and estimate the burden of potentially preventable atherosclerotic cardiovascular diseases (ASCVD) events. Methods and results Using nationally representative data from the 2017 to 2020 National Health and Nutrition Examination Survey, statin use was assessed in primary prevention groups: high ASCVD risk ≥ 20%, LDL-cholesterol (LDL-C) ≥ 190 mg/dL, diabetes aged 40–75 years, intermediate ASCVD risk (7.5 to Conclusion Statin use for primary and secondary prevention of ASCVD remains suboptimal. Bridging the therapeutic gap can prevent ∼1 million ASCVD events over the subsequent 10 years for the primary prevention group. Social determinants of health such as access to care and healthcare coverage were associated with less statin treatment. Novel interventions to improve statin prescription and adherence are needed.

Objectives To evaluate the relationship between disease features in Friedreich ataxia and aberrant glucose metabolism. Methods Fasting glucose, fasting insulin and random HbA1C were obtained in 158 patients with Friedreich ataxia. Regression analysis evaluated glucose, insulin, and homeostatic model assessment (HOMA) of insulin resistance (IR) and beta-cell function (s) in relation to age, BMI, sex, and genetic severity. Categorical glucose values were analyzed in relation to other FRDA-associated disease characteristics. Results In the FRDA cohort, age and GAA repeat length predicted fasting glucose and HbA1c levels (accounting for sex and BMI), while insulin and HOMA-IR were not predicted by these parameters. Within the cohort, average BMI was consistently lower than the national average by age and was marginally associated with insulin levels and HOMA-IR. Within juvenile subjects, insulin and HOMA-IR were predicted by age. Controlling for age and genetic severity, diabetes-related measures were not independent predictors of any quantitative measure of disease severity in FRDA. Glucose handling properties were also predicted by the presence of a point mutation, with 40% of individuals heterozygous for point mutations having diabetes, compared to 4.3% of subjects who carried two expanded GAA repeats. Interpretation In FRDA, aberrant glucose metabolism is linked to increasing age, longer GAA repeat length on the shorter allele, frataxin point mutations, and increasing BMI. The effect of age to some degree may be mediated through changes in BMI, with increasing age associated with increases in BMI, and with HOMA-IR and insulin increases in children.

Electrocardiographic (ECG) findings in Friedreich ataxia and their relation to disease characteristics have not been well described. In this retrospective cross-sectional study, the authors reviewed baseline ECGs from 239 children and adults with Friedreich ataxia. ECG abnormalities—assessed in relation to participant age, sex, shorter guanine-adenine-adenine triplet repeat length, age of disease onset, and functional disability score—were found in 90% of subjects, including nonspecific ST-T wave changes (53%), right axis deviation (32%), left ventricular hypertrophy (19%), and right ventricular hypertrophy (13%). Female sex and shorter guanine-adenine-adenine repeat lengths were associated with a normal ECG ( P = .004 and P = .003). Males and those of younger age were more likely to show ventricular hypertrophy ( P = .006 and P = .026 for left ventricular hypertrophy and P < .001 and P = .001 for right). Neurologic status as measured by the functional disability score did not predict ECG abnormalities.

The autosomal-recessive disorder Friedreich's ataxia is characterized by progressive ataxia, often in association with cardiomyopathy. The most frequent cause of death is cardiac dysfunction, reflecting congestive heart failure, ventricular arrhythmias and cardio-embolic stroke. With the discovery of the underlying genetic mutation, a variety of novel therapies are now progressing into clinical trials. Consequently, it is crucial to understand the features of cardiomyopathy in this disease and how new treatments may improve cardiac function. The present artcle reviews the molecular basis of the disease, the clinical features of cardiomyopathy in Friedreich's ataxia and the upcoming therapies.

Although Friedreich ataxia (FA) is associated with cardiomyopathy, the severity and evolution of cardiac disease is poorly understood. To identify factors predicting cardiomyopathy in FA, we assessed echocardiograms from a large heterogenous cohort and their relation to disease traits. The most recent echocardiograms from 173 subjects with FA were analyzed in a core laboratory to determine their relation to disease duration, subject age, age of onset, functional disability score, and GAA repeat length. Mean age of the cohort was 19.7 years, mean age of disease onset was 10.6 years, and mean shorter GAA length was 681 repeats. Echocardiograms collectively illustrated systolic dysfunction, diastolic dysfunction, and hypertrophy. Measurements of hypertrophy correlated moderately with each other (r = 0.39 to 0.79) but not with measurements of diastolic dysfunction (r0.35). Diastolic measurements correlated poorly with each other, although 26% of the cohort had multiple diastolic abnormalities. The most common diastolic dysfunction classification was pseudonormalization. Classification of diastolic dysfunction was predicted by GAA repeat length but not by age or gender. Ejection fraction was below normal in 20% of the cohort. In linear regression analysis, increasing age predicted decreasing ejection fraction. Functional disability score, a measurement of neurologic ability, did not predict any echocardiographic measurements. In conclusion, hypertrophy and diastolic and systolic dysfunctions occur in FA and are substantially independent; diastolic dysfunction is the most common abnormality with most patients having an assigned diastolic dysfunction class of pseudonormalization.

Background Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia of all four limbs, dysarthria, areflexia, and cardiomyopathy. At present, baseline values of cardiac troponin I are unknown among Friedreich ataxia subjects. Methods In this study, we evaluated baseline plasma cardiac troponin I levels among a cross-sectional cohort of 49 pediatric and adult Friedreich ataxia subjects without active arrhythmia, chest pain or features of acute coronary syndrome at the time of sampling. We also reviewed baseline electrocardiograms from 45 of these subjects. Results Troponin I values were elevated above the 99th percentile population cutoff in 46.9% of all subjects, with 16.3% of asymptomatic subjects having levels typically seen during an acute myocardial infarction. In logistic regression models, younger age and an earlier disease onset predicted higher serum cardiac troponin I values. Only weak correlations were seen between cardiac troponin I values and echocardiogram parameters, including ejection fraction. Additionally, 82.2% of subjects also had abnormal baseline electrocardiograms. Conclusion The present study demonstrates that both abnormal electrocardiograms and elevated serum cardiac troponin I values may be common baseline characteristics seen in Friedreich ataxia subjects. Further longitudinal studies will allow for a better understanding of the cause and prognostic implications of elevated levels, as well as the clinical utility of serum cardiac troponin I testing in Friedreich ataxia.

Objective: Friedreich ataxia (FA) is the most common ataxia and results from an expanded GAA repeat in the first intron of FXN. This leads to epigenetic modifications and reduced frataxin. We investigated the relationships between genetic, epigenetic, and clinical parameters in a large case–control study of FA. Methods: Clinical data and samples were obtained from individuals with FA during annual visits to our dedicated FA clinic. GAA expansions were evaluated by polymerase chain reaction (PCR) and restriction endonuclease digest. DNA methylation was measured using bisulfite-based EpiTYPER MassARRAY (Sequenom, San Diego, CA). FXN expression was determined using real-time reverse transcriptase PCR. Significant correlations between the different parameters were examined using the nonparametric Spearman rank correlation coefficient, as well as univariate and multivariate regression modeling. Results: Characteristic DNA methylation was identified upstream and downstream of the expansion, and validated in an independent FA cohort. Univariate and multivariate analyses showed significant inverse correlations between upstream methylation and FXN expression, and variation in downstream methylation and age of onset. FXN expression also inversely correlated with the Friedreich Ataxia Rating Scale score, an indicator of disease severity. Interpretation: These novel findings provide compelling evidence for the link between the GAA expansion, the DNA methylation profile, FXN expression, and clinical outcome in FA. Epigenetic profiling of FXN could be used to gain greater insight into disease onset and progression, but also as a biomarker to learn more about specific treatment responses and pharmacological mechanism(s). This work also highlights the potential for developing therapies aimed at increasing frataxin levels to treat this debilitating disease. ANN NEUROL 2012