Citations

Cervical arthrography was performed on 13 patients with putative cervical facet symptoms. Under fluoroscopic control, injection of radiopaque dye, local anesthetic, and depot steroid into the affected joint capsule was performed without complication. Eleven of the 13 patients had partial to complete pain relief during the 2-week to 6-month followup period.

Abstract With aging, somatic mutations in hematopoietic stem and progenitor cells (HSPC) can give rise to clonal hematopoiesis of indeterminate potential (CHIP), a premalignant state associated with diverse age-related diseases. Here we report the largest multi-ancestry genome-wide analysis of CHIP to date (N = 1,018,305), including individuals of African (N = 85,978), Admixed American (N = 191,371), East Asian (N = 13,532), European (N = 694,015), and South Asian (N = 13,193) ancestry. Multi-ancestry meta-analyses identified 72 genome-wide significant loci, including 44 novel associations implicating genes such as AFF1 , ATF7IP , ATP8B4 , BCL2 , CEBPA , CYRIA , DNM2 , ELF1 , NKX2-3 , PIK3CB , PRDM16 , RPN1 , TERC , and TRIM4 . Notably, variants at MECOM and PHF20L1 showed opposite allelic effects between DNMT3A - and non- DNMT3A -driven CHIP, highlighting driver-specific germline influences. Implicated loci converge on pathways regulating telomere maintenance, cell-cycle control, hematopoietic transcription, DNA damage response and immune signaling. These findings support a model in which germline variation both expands the HSPC pool and biases clonal selection in a driver-dependent manner, providing a mechanistic basis for inter-individual heterogeneity in CHIP. Phenome-wide association analyses further linked CHIP to hematologic, neoplastic, and circulatory traits, with enrichment across hematopoietic and non-hematopoietic cell types. Together, this work expands the genomic and phenomic landscape of CHIP and reveals germline–somatic interactions that shape clonal evolution during aging.

Background: The 2013 ACC/AHA Cholesterol Guidelines departed from prior ATPIII guidelines, recommending statin treatment based on patients’ predicted 10-year ASCVD risk and de-emphasizing LDL-C targets. However, the degree to which these new guidelines have been adopted by clinicians in community practice is unknown. Methods: We surveyed 522 clinicians in 133 cardiology, primary care, and endocrinology practices participating in the Patient and Provider Assessment of Lipid Management (PALM) Registry. Clinicians were asked about their likelihood of prescribing statins in 4 hypothetical patient scenarios. Results: Among responders, 79% were physicians (60% cardiologists, 38% primary care or general practice, 2% endocrinology), 18% were advanced practice providers, and 3% trainees. When queried, 73% of providers reported primarily using the 2013 ACC/AHA Guidelines to guide lipid management. However, only half reported “often” or “always” calculating 10-year ASCVD risk to aid lipid management decisions for primary prevention. When presented with a high 10-year ASCVD risk patient (>15%) with a high LDL-C (150 mg/dL), 92% of providers recommended statins. Similarly, 83% of providers would use statins in a diabetic patient with a LDL-C of 140 mg/dL. Yet, only 37% reported they would prescribe a statin to an older adult (age 70) for whom guidelines recommend statin based on high 10-year ASCVD risk alone (10.1%). And up to 40% would prescribe a statin to a younger (age 40) with a low 10-year risk, but a high LDL (165 mg/dL) who would not otherwise meet criteria for statin therapy under the new guidelines. Cardiologists and non-cardiologists were similarly likely prescribe statins in most scenarios with the exception of to the younger patient with elevated LDL-C were cardiologists used statins more commonly (32% vs. 42%. OR 1.5, 95% CI 1.1-2.2, p=0.02). Conclusion: Initial survey results show that while most clinicians claim adoption of the 2013 ACC/AHA Guidelines, reported practices are not always adherent to these guidelines. Providers do not always calculate 10-year ASCVD risk to guide lipid management and many do not prescribe statins to patients eligible based on 10-year ASCVD risk.

Abstract BACKGROUND Dyslipoproteinemias can be classified by their distinct lipoprotein patterns, which helps determine atherosclerotic cardiovascular disease (ASCVD) risk and directs lipid management but this has required advanced laboratory testing. OBJECTIVE To develop a new algorithm for classifying lipoprotein disorders that only relies on the standard lipid panel. METHODS Lipid thresholds for defining the different lipoprotein phenotypes were derived for Non-High-Density Lipoprotein-Cholesterol (NonHDL-C) and Triglycerides (TG) to be concordant when possible with the current US Multi-Society guidelines for blood cholesterol management. RESULTS The new classification method categorizes patients into all the classical Fredrickson-like phenotypes except for Type III dysbetalipoproteinemia. In addition, a new hypolipidemic phenotype (Type VI) due to genetic mutations in apoB-metabolism is described. The validity of the new algorithm was confirmed by lipid analysis by NMR (N = 11,365) and by concordance with classification by agarose gel electrophoresis/beta-quantification (N = 5504). Furthermore, based on the Atherosclerosis Risk in Communities (ARIC) cohort (N = 14742), the lipoprotein phenotypes differ in their association with ASCVD (TypeV > IIb > IVb > IIa > IVa > normolipidemic) and can be used prognostically as risk enhancer conditions in the management of patients. CONCLUSIONS We describe a clinically useful lipoprotein phenotyping system that is only dependent upon the standard lipid panel. It, therefore, can be easily implemented for increasing compliance with current guidelines and for improving the care of patients at risk for ASCVD.

Background: Prior ATPIII lipid guidelines recommended statin therapy for patients with clinical ASCVD to achieve low density lipoprotein cholesterol (LDL-C) targets, while the 2013 ACC/AHA lipid guidelines recommend high-intensity statin therapy for all ASCVD patients. How closely these recommendations are followed in routine clinical practice is unknown. Methods: We evaluated statin use, intensity, and LDL-C values in 1,483 patients with ASCVD (coronary heart disease, cerebrovascular disease, and peripheral arterial disease) enrolled and seen serially at 62 geographically dispersed US cardiology and primary care clinics in the Patient and Provider Assessment of Lipid Management (PALM) Registry between May - September 2015. Factors associated with high intensity statin use (atorvastatin ≥40 mg or rosuvastatin ≥20 mg daily) and LDL-C <70 mg/dL were evaluated in multivariable logistic regression. Results: Of 1,483 ASCVD patients, 86.2% were on a statin, but only 31.4% were on a high-intensity statin. Overall, 64.0% had an LDL-C <100 mg/dL, but only 29.0% had an LDL-C <70 mg/dL. Factors associated with high-intensity statin use in multivariable regression were younger age (OR 0.74 per 10 year increase, p<0.001, 95% CI 0.66-0.83), male sex (OR 1.69, p<0.001, 95% CI, 1.32-2.16), cerebrovascular disease (OR 1.55, p=0.008, 95% CI 1.12-2.13), coronary heart disease (OR 2.42, p<0.001, 95% CI 1.67-3.50), and being seen by a cardiologist (OR 1.35, p =0.04, 95% CI 1.01-1.81). Factors associated with an increased likelihood of LDL-C<70 were male sex (OR 1.55, p=0.001, 95% CI 1.20-2.01), white (OR 1.62, p=0.03, 95% CI 1.04-2.5-, diabetes (OR 1.64, p<0.001, 95% CI 1.29-2.09) and being seen by a cardiologist (OR 1.94, p<0.001, 95% CI 1.41-2.67). Discussion: Substantial gaps in care remain for secondary prevention of ASCVD despite simplified recommendations. While the majority of patients with ASCVD in community practice are on a statin, only one-third are on high intensity statins and over two-thirds have LDL ≥70 mg/dL.

Introduction: Statin dose guidelines for PAD patients are based on coronary artery disease and stroke data. The aim of our study was to determine the effect of statin dose (based on 2013 ACC/AHA guidelines) on PAD outcomes of amputation and mortality. Methods: Patients with PAD in the Veterans Affairs database were identified from 2003-2014. The exposure was highest statin dose usage (none, low-moderate and high intensity) around diagnosis of PAD (within 1 year). The outcomes were risk of incident amputation (below knee or above knee) and mortality at 1, 3 and 5 years. The effect of statin dose on the two outcomes was also analyzed using Cox proportional hazards modeling to adjust for covariates. Results: In 208,275 patients with PAD [Males: 98.1%; Mean age: 67.4 yrs (SD 9.9)], 17,643 amputations and 99,951 deaths occurred in a median follow up of 5.2 years. Almost a quarter (27.7%) of patients were not on a statin while 30.4% were on simvastatin 80 mg (no longer recommended due to drug toxicity). The risk of incident amputation declined significantly at the high intensity statin dose as seen in Table 1. In Cox models adjusting for age, gender, race, comorbidities, cholesterol levels and creatinine, the high intensity statins were associated with lower amputation risk and mortality as compared to no statin [HR 0.67; 95% CI (0.63, 0.72) and HR 0.71; 95% CI (0.68, 0.73), respectively]. Low-moderate-dose statins also had significant but smaller reductions in risk of amputation and mortality [HR amputation 0.78 (0.75, 0.82), HR death 0.78 (0.77, 0.80)]. Conclusion: This is one of the largest population based studies to examine the effect of statins on long-term PAD outcomes and the first to explore the dose-dependent effect of statins on amputation and mortality. High intensity statins are associated with a significant reduction in limb loss and mortality in PAD patients followed by a smaller risk reduction by low-moderate intensity statins as compared to no statin therapy.