Low-Density Lipoprotein Cholesterol Levels in Coronary Artery Disease Patients: Opportunities for Improvement.

Background: We sought to characterize the level of LDL-C control and identify opportunities for improvement and characteristics of patients who were undertreated. Methods: Study patients were from a large multihospital system, age <90, with documentation of at least two encounters with a CAD diagnosis or procedure before a first measured LDL-C level and a last recorded LDL-C measurement over a minimum six-month (median = 22 months, IQR = 15-26 months) follow-up from January 2017 to September 2019. Linear regression analysis for last recorded LDL-C level was used to analyze the effects of statin intensity and patient characteristics. Results: Among 15,111 eligible patients, mean age was 68.4 (SD = 10.8), 68.7% were male, and 79.4% were non-Hispanic White. At follow-up, 87.8% of patients were prescribed a statin, 9.7% were on ezetimibe, and 0.5% were on a PCSK9 inhibitor. Mean LDL-C at follow-up was 75.6 mg/dL and 45.5% of patients were on high-intensity treatment. Higher LDL-C values were associated with female sex, younger patients, non-Hispanic Black patients, high poverty or out of state zip code, Medicaid, or angina as the qualifying diagnosis. For 332 clinicians with >10 patients in the cohort, mean last recorded LDL-C values ranged from 47 to 102 mg/dL. Conclusions: There were important variations in LDL-C control between patients in our health system with the same indication for treatment. Variation in treatment among physicians is an area ripe for quality improvement interventions. This study may be easily reproduced by other medical centers and used for highlighting both patient and physician opportunities for improvement.

Inflammation, coronary plaque progression, and statin use: A secondary analysis of the Risk Stratification with Image Guidance of HMG CoA Reductase Inhibitor Therapy (RIGHT) study.

BACKGROUND: Statin treatment is a potent lipid-lowering therapy associated with decreased cardiovascular risk and mortality. Recent studies including the PARADIGM trial have demonstrated the impact of statins on promoting calcified coronary plaque. HYPOTHESIS: The degree of systemic inflammation impacts the amount of increase in coronary plaque calcification over 2 years of statin treatment. METHODS: A subgroup of 142 participants was analyzed from the Risk Stratification with Image Guidance of HMG CoA Reductase Inhibitor Therapy (RIGHT) study (NCT01212900), who were on statin treatment and underwent cardiac computed tomography angiography (CCTA) at baseline and 2-year follow-up. This cohort was stratified by baseline median levels of high-sensitivity hs-CRP and analyzed with linear regressions using Stata-17 (StataCorp). RESULTS: In the high versus low hs-CRP group, patients with higher baseline median hs-CRP had increased BMI (median [IQR]; 29 [27-31] vs. 27 [24-28]; p < .001), hypertension (59% vs. 41%; p = .03), and LDL-C levels (97 [77-113] vs. 87 [75-97] mg/dl; p = .01). After 2 years of statin treatment, the high hs-CRP group had significant increase in dense-calcified coronary burden versus the low hs-CRP group (1.27 vs. 0.32 mm2 [100×]; p = .02), beyond adjustment (ß = .2; p = .03). CONCLUSIONS: Statin treatment over 2 years associated with a significant increase in coronary calcification in patients with higher systemic inflammation, as measured by hs-CRP. These findings suggest that systemic inflammation plays a role in coronary calcification and further studies should be performed to better elucidate these findings.

Chronic inflammatory diseases and coronary heart disease: Insights from cardiovascular CT.

Epidemiological and clinical studies have demonstrated a consistent relationship between increased systemic inflammation and increased risk of cardiovascular events. In chronic inflammatory states, traditional risk factors only partially account for the development of coronary artery disease (CAD) but underestimate total cardiovascular risk likely due to the residual risk of inflammation. Computed coronary tomography angiography (CCTA) may aid in risk stratification by noninvasively capturing early CAD, identifying high risk plaque morphology and quantifying plaque at baseline and in response to treatment. In this review, we focus on reviewing studies on subclinical atherosclerosis by CCTA in individuals with chronic inflammatory conditions including rheumatoid arthritis (RA), systemic lupus erythematous (SLE), human immunodeficiency virus (HIV) infection and psoriasis. We start with a brief review on the role of inflammation in atherosclerosis, highlight the utility of using CCTA to delineate vessel wall and plaque characteristics and discuss combining CCTA with laboratory studies and emerging technologies to complement traditional risk stratification in chronic inflammatory states.

Subclinical Liver Disease Is Associated with Subclinical Atherosclerosis in Psoriasis: Results from Two Observational Studies.

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n = 76 psoriasis participants and 76 controls), nonalcoholic fatty liver disease, assessed by the sonographic hepatorenal index, was more prevalent in psoriasis than in controls (61% vs. 45%; P = 0.04). Participants with psoriasis with nonalcoholic fatty liver disease had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than participants with psoriasis without nonalcoholic fatty liver disease (61% vs. 23%; P = 0.006) and controls with nonalcoholic fatty liver disease (61% vs. 32%; P < 0.05). Sonographic hepatorenal index was a determinant of subclinical atherosclerosis in psoriasis (OR = 3.5; P = 0.01). In the United States cohort (n = 162 participants with psoriasis who underwent positron emission tomography and coronary computed tomography angiography), those with high hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake had higher noncalcified (1.3 [0.49 mm2] vs. 1.0 [0.40 mm2]), fibrofatty (0.23 [0.15 mm2] vs. 0.11 [0.087 mm2]), and lipid-rich necrotic core (4.3 [2.3 mm2] vs. 3.0 [1.7 mm2]) coronary burden (all P < 0.001). Hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake associated with noncalcified (ß = 0.28; P < 0.001), fibrofatty (ß = 0.49; P < 0.001), and lipid-rich necrotic core (ß = 0.28; P = 0.003) burden. These results show the downstream cardiovascular effects of subclinical liver disease in psoriasis.

Heightened splenic and bone marrow uptake of 18F-FDG PET/CT is associated with systemic inflammation and subclinical atherosclerosis by CCTA in psoriasis: An observational study.

BACKGROUND AND AIMS: Psoriasis is an immune-mediated inflammatory disease with increased risk of myocardial infarction. Preclinical studies in psoriasis models show an association between chronic inflammation and immune cell proliferation in the spleen and bone marrow (BM). We sought to test the hypothesis that splenic and BM 18F-fluorodeoxyglucose (18F-FDG) uptake is heightened in psoriasis and that higher uptake associates with systemic inflammation and subclinical atherosclerotic disease measures in this cohort. METHODS: Multimodality imaging and biomarker assays were performed in 240 participants (210 with psoriasis and 30 healthy). Splenic and BM uptake was obtained using 18F-FDG positron emission tomography/computed tomography (PET/CT). Coronary artery plaque characteristics including non-calcified burden (NCB) and lipid rich necrotic core (LRNC) were quantified using a dedicated software for CT angiography. All analyses were performed with StataIC 16 (Stata Corp., College Station, TX, USA). RESULTS: Splenic and BM 18F-FDG uptake was increased in psoriasis (vs. healthy volunteers) and significantly associated with proatherogenic lipids, immune cells and systemic inflammation. Higher splenic 18F-FDG uptake associated with higher total coronary burden (ß = 0.37; p<0.001), NCB (ß = 0.39; p<0.001), and LRNC (ß = 0.32; p<0.001) in fully adjusted models. Similar associations were seen for BM 18F-FDG uptake in adjusted models (ß = 0.38; ß = 0.41; ß = 0.24; respectively, all p<0.001). CONCLUSIONS: Heightened splenic and BM uptake of 18F-FDG is associated with proatherogenic lipids, immune cells, inflammatory markers and coronary artery disease. These findings provide insights into atherogenic mechanisms in psoriasis and suggest that immune cell proliferation in the spleen and BM is associated with subclinical atherosclerosis.

The relationship between systemic inflammation and increased left ventricular mass is partly mediated by noncalcified coronary artery disease burden in psoriasis.

OBJECTIVE: Increased left ventricular (LV) mass is an important precursor to heart failure. Inflammation plays an important role in increasing LV mass. However, the contribution of subclinical coronary artery disease (CAD) to the inflammation-LV mass relationship is unknown. In subjects with psoriasis, a chronic inflammatory skin disease, we evaluated if systemic inflammation assessed by plasma glycoprotein A (GlycA) associated with LV mass measured on coronary CT angiography (CCTA). Additionally, we analyzed whether this relationship was mediated by early CAD assessed as noncalcified coronary burden (NCB). METHODS: We performed an observational longitudinal study of 213 subjects with psoriasis free of known cardiovascular disease, 189 of whom were followed over one year. All participants had GlycA measurements by nuclear magnetic resonance spectroscopy and LV mass and NCB quantified by CCTA. RESULTS: The cohort had a mean age of 50.3 (±12.9) years and 59% were male. There was moderate psoriasis severity and low cardiovascular risk. LV mass increased by GlycA tertiles [1st tertile:24.6 g/m2.7(3.8), 2nd tertile:25.5 g/m2.7(3.8), 3rd tertile:27.7 g/m2.7(5.5), p<0.001]. Both GlycA (ß=0.24, p = 0.001) and NCB (ß=0.50, p<0.001) associated with LV mass in models adjusted for age, sex, hypertension, hypertension therapy, lipid therapy, biologic therapy for psoriasis, waist:hip ratio, psoriasis disease duration and severity. In multivariable-adjusted mediation analyses, NCB accounted for 32% of the GlycA-LV mass relationship. Finally, over one year, change in NCB independently associated with change in LV mass (ß=0.25, p = 0.002). CONCLUSIONS: Both systemic inflammation and coronary artery NCB were associated with LV mass beyond cardiovascular risk factors in psoriasis. Furthermore, a substantial proportion of the inflammatory-LV mass relationship was mediated by NCB. These findings underscore the possible contribution of early coronary artery disease to the relationship between systemic inflammation and LV mass.

Abdominal subcutaneous adipose tissue negatively associates with subclinical coronary artery disease in men with psoriasis.

OBJECTIVE: Understand the relationship between abdominal subcutaneous adipose tissue (ASAT) and coronary atherosclerosis defined as noncalcified and lipid-rich necrotic core burden in psoriasis. METHODS: We performed a cross-sectional study of 232 participants (92 women) with psoriasis and without known cardiovascular disease. Participants underwent coronary computed tomography angiography to characterize coronary atherosclerosis burden and low dose abdominal computed tomography to quantify subcutaneous and visceral adipose tissue. Fat depot volumes were first adjusted for each participant's BMI (ASATadjBMI). RESULTS: In women, there was a positive correlation between ASATadjBMI and systemic inflammation as assessed by hs-C-reactive protein (r=0.30; p=.004) and GlycA (r=0.29; p=.007) as well as total cholesterol (r=0.24; p=.02) and low-density lipoprotein cholesterol (r=0.22; p=.04). In men, ASATadjBMI correlated with hs-C-reactive protein (r=0.18; p=.04) and insulin resistance (r=0.17; p=.04). In models fully adjusted for traditional cardiovascular risk factors, ASATadjBMI negatively associated with noncalcified and lipid-rich necrotic core burden in men (ß= -0.17; p=.03, ß= -0.20; p=.03, respectively), but not women (ß= -0.06; p=.57, ß= 0.09; p=.49, respectively) with psoriasis. CONCLUSIONS: For a given BMI, ASAT negatively associated with coronary atherosclerosis burden in male participants with psoriasis. The observed sex-specific effects warrant further study of ASAT in states of chronic inflammation.

Psoriasis and Cardiometabolic Diseases: The Impact of Inflammation on Vascular Health.

Psoriasis is a common chronic inflammatory condition associated with a higher risk of cardiovascular disease. Psoriasis confers a dose-dependent increase in risk for the metabolic syndrome and its components. The metabolic syndrome and its components have been associated with higher coronary atherosclerosis in psoriasis and cardiovascular events in the general population. In this review, we discuss the role of inflammation and psoriasis in cardiometabolic diseases with a focus on the metabolic syndrome and its components. We highlight the relationship between psoriasis and important cardiovascular risk factors encompassed by obesity, dyslipidemia, insulin resistance and hypertension. Furthermore, we briefly highlight literature on anti-inflammatory therapies and their impact on the components of the metabolic syndrome as well as directly quantified coronary atherosclerosis burden.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.

The application of molecular imaging to advance translational research in chronic inflammation.

Over the past several decades, molecular imaging techniques to assess cellular processes in vivo have been integral in advancing our understanding of disease pathogenesis. 18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) imaging in particular has shaped the field of atherosclerosis research by highlighting the importance of underlying inflammatory processes that are responsible for driving disease progression. The ability to assess physiology using molecular imaging, combining it with anatomic delineation using cardiac coronary angiography (CCTA) and magnetic resonance imaging (MRI) and lab-based techniques, provides a powerful combination to advance both research and ultimately clinical care. In this review, we demonstrate how molecular imaging studies, specifically using 18-FDG PET, have revealed that early vascular disease is a systemic process with multiple, concurrent biological mechanisms using inflammatory diseases as a basis to understand early atherosclerotic mechanisms in humans.

Predicting Obstructive Sleep Apnea Status With the Reflux Symptom Index in a Sleep Study Population.

OBJECTIVES/HYPOTHESIS: Otolaryngologic symptoms of obstructive sleep apnea (OSA) and their diagnostic utility are not well studied. We aimed to elucidate the prevalence of otolaryngologic symptoms among patients being evaluated for OSA. Given findings that the Reflux Symptom Index (RSI) was strongly associated with OSA status, we evaluated the diagnostic utility of the RSI for predicting OSA status. STUDY DESIGN: Cross-sectional. METHODS: We recruited 101 adults presenting for ambulatory polysomnograms to the Northwestern Sleep Disorders Center from July 2017 to July 2018. The Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Leicester Cough Questionnaire (LCQ), RSI, Gastroesophageal Reflux Disease Questionnaire, Sino-Nasal Outcome Test-22, Nasal Obstruction Symptom Evaluation, Eustachian Tube Dysfunction Questionnaire 7, and Headache Impact Test were administered. Polysomnogram results were subsequently obtained. Patients with OSA (apnea-hypopnea index ≥ 5) and without OSA were compared. RESULTS: Of the 101 participants, 98 had valid sleep study results. Of those, 72 were diagnosed with OSA and 26 were not. The two groups differed significantly in age and body mass index (BMI). Of the questionnaires, only the RSI and LCQ means differed significantly, with worse symptoms in the OSA group (P = .003 and .014, respectively). Upon univariate regression, age, BMI, and RSI were associated with OSA status. Using regression coefficients, a clinical score of 2 (RSI) + 1.5 (BMI) + age yielded a diagnostic model (C-statistic = 0.807, P < .001). A threshold score of 104.21 was 76.4% sensitive and 73.1% specific. CONCLUSIONS: Patients with OSA have worse symptoms of laryngopharyngeal reflux as measured by the RSI. The addition of the RSI to the recognized factors of age and BMI improves diagnostic utility for OSA. LEVEL OF EVIDENCE: 2 Laryngoscope, 2020.

Measuring the health utility of chronic eustachian tube dysfunction.

OBJECTIVE: To assess the health utility of chronic Eustachian tube dysfunction (ETD). METHODS: This is a prospective study of 53 patients with chronic ETD recruited from a tertiary clinic from April 2017 to July 2018. The 7-Item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) was administered, and health utility was evaluated using the EuroQol-5 Dimensions-3 Level Instrument (EQ-5D-3L), the visual analogue scale (VAS), time tradeoff (TTO), and standard gamble (SG). Participants were grouped into medical or procedural management groups. One-week follow-up included repeated health utility measures and ETDQ-7. RESULTS: Fifty-three patients were included in the final analysis. Of those, 34 were managed medically, and 19 received myringotomies ± PE tubes. The mean baseline ETDQ-7 was 4.26 ± 1.31; whereas health utility measures were different depending on the method utilized: EQ-5D-3L 0.90 ± 0.11; VAS 0.76 ± 0.21; TTO 0.85 ± 0.23; and SG 0.94 ± 0.11 (P < .001). There was a significant change in ETDQ-7 (P = .001) and TTO (P = .011) scores posttreatment. On the ETDQ-7, question 2 (pain in the ears) was significantly associated with VAS (P = .032), and question 4 (ear symptoms during a cold or sinusitis) was significantly associated with TTO (P = .006). CONCLUSION: Chronic ETD has a significant burden on quality of life, with a health utility similar to gastroesophageal reflux disease and moderate asthma. Although treatment-related changes are measurable using disease-specific quality-of-life measures, only TTO was significantly changed after treatment. Health utility seemed to depend on the method of measurement but provided a benchmark for evaluating cost-effectiveness of innovations to manage ETD. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:E39-E44, 2020.