Burden and predictors of statin use in primary and secondary prevention of atherosclerotic vascular disease in the US: from the National Health and Nutrition Examination Survey 2017-2020.

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 <20%) with ≥1 ASCVD risk enhancer and secondary prevention group: established ASCVD. Atherosclerotic cardiovascular disease risk was estimated using pooled cohort equations. We estimated 70 million eligible individuals (2.3 million with LDL-C ≥ 190 mg/dL; 9.4 million with ASCVD ≥ 20%; 15 million with diabetes and age 40-75years; 20 million with intermediate ASCVD risk and ≥1 risk enhancers; and 24.6 million with established ASCVD), about 30 million were on statin therapy. The proportion of individuals not on statin therapy was highest in the isolated LDL-C ≥ 190 mg/dL group (92.8%) and those with intermediate ASCVD risk plus enhancers (74.6%) followed by 59.4% with high ASCVD risk, 54.8% with diabetes, and 41.5% of those with established ASCVD groups. Increasing age and those with health insurance were more likely to be on statin therapy in both the primary and secondary prevention categories. Individuals without a routine place of care were less likely to be on statin therapy. A total of 385 000 (high-intensity statin) and 647 000 (moderate-intensity statin) ASCVD events could be prevented if all statin-eligible individuals were treated (and adherent) for primary prevention over a 10-year period. 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.

A case off TTP temporally associated with cocaine use: Implications for treatment of suspected DITMA.

Thrombotic microangiopathies are rare diseases associated with significant morbidity and mortality. The treatment of thrombotic thrombocytopenic purpura (TTP) and drug-induced thrombotic microangiopathy (DITMA) remains a diagnostic dilemma as they present similarly but respond differently to standard treatment with plasma exchange. TTP is a deficiency of a disintegrin and metalloprotease with thrombospondin type 1 motif 13 resulting in von Willebrand factor aggregates. DITMA is due to vascular and platelet toxicity. Our case contradicts a notion in current literature that suggests supportive therapy when there is high suspicion for DITMA. We present what appears to be the second published case of cocaine temporally associated with TTP. Our case responded to therapy. We propose this case should influence weighing the risks and benefits of treatment of suspected DITMA and reinforces current official guidelines that suggest treating cases of suspected DITMA as TTP until the diagnosis is confirmed.

Longitudinal strain in Friedreich Ataxia: a potential marker for early left ventricular dysfunction.

BACKGROUND: Friedreich's ataxia (FRDA) is a neurodegenerative disorder resulting from deficiency of frataxin, characterized by cardiac hypertrophy associated with heart failure and sudden cardiac death. However, the relationship between remodeling and novel measures of cardiac function such as strain, and the time-dependent changes in these measures are poorly defined. METHODS AND RESULTS: We compared echocardiographic parameters of cardiac size, hypertrophy, and function in 50 FRDA patients with 50 normal controls and quantified the following measures of cardiac remodeling and function: left ventricular (LV) volumes, mass, relative wall thickness (RWT), ejection fraction (EF), and myocardial strain. Linear regression analysis was used to identify significant differences in echocardiographic parameters in FRDA compared with normal subjects. In analyses adjusted for age, sex, and body surface area, significant differences were observed between parameters of remodeling (LV mass, RWT, and volumes) and function in FRDA patients compared with controls. In particular, longitudinal strain was significantly decreased in FRDA patients compared with controls (-12.4% vs. -16.0%, P < 0.001), despite similar and normal left ventricular ejection fraction (LVEF). Over 3 years of follow-up, there was no change in strain, LV size, LV mass, or LVEF among FRDA patients. CONCLUSION: Longitudinal strain is reduced in FRDA despite normal LVEF, indicative of subclinical cardiac dysfunction. Given late declines in LVEF in FRDA, longitudinal strain may provide an earlier index of myocardial dysfunction in FRDA.

Elevation of serum cardiac troponin I in a cross-sectional cohort of asymptomatic subjects with Friedreich ataxia.

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.

Management and therapy for cardiomyopathy in Friedreich's ataxia.

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.

Cross-sectional analysis of electrocardiograms in a large heterogeneous cohort of Friedreich ataxia subjects.

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.

Friedreich ataxia clinical outcome measures: natural history evaluation in 410 participants.

Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia, dysarthria, and areflexia. The authors report the progress of a large international noninterventional cohort (n = 410), tracking the natural history of disease progression using the neurologic examination-based Friedreich Ataxia Rating Scale. The authors analyzed the rate of progression with cross-sectional analysis and longitudinal analysis over a 2-year period. The Friedreich Ataxia Rating Scale captured disease progression when used at 1 and 2 years following initial evaluation, with a lower ratio of standard deviation of change to mean change over 2 years of evaluation. However, modeling of disease progression identified substantial ceiling effects in the Friedreich Ataxia Rating Scale, suggesting this measure is most useful in subjects before maximal deficit is approached.

FXN methylation predicts expression and clinical outcome 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.

Analysis of echocardiograms in a large heterogeneous cohort of patients with friedreich ataxia.

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 (r <0.35). 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.