The impact of carbohydrate restriction-induced elevations in low-density lipoprotein cholesterol on progression of coronary atherosclerosis: the ketogenic diet trial study design.

BACKGROUND: Despite innovations in pharmacotherapy to lower lipoprotein cholesterol and apolipoprotein B, risk factors for atherosclerotic cardiovascular disease (ASCVD), ASCVD persists as the leading global cause of mortality. Elevations in low-density lipoprotein cholesterol (LDL-C) are a well-known risk factor and have been a main target in the treatment of ASCVD. The latest research suggests that ketogenic diets are effective at improving most non-LDL-C/apolipoprotein B cardiometabolic risk factors. However, ketogenic diets can induce large increases in LDL-C to >190 mg/dl in some individuals. Interestingly, these individuals are often otherwise lean and healthy. The influence of increased levels of LDL-C resulting from a carbohydrate-restricted ketogenic diet on the progression of atherosclerosis in otherwise metabolically healthy individuals is poorly understood. This observational study aims to assess and describe the progression of coronary atherosclerosis in this population within 12 months. METHODS: Hundred relatively lean individuals who adopted ketogenic diets and subsequently exhibited hypercholesterolemia with LDL-C to >190 mg/dl, in association with otherwise good metabolic health markers, were enrolled and observed over a period of 12 months. Participants underwent serial coronary computed tomography angiography scans to assess the progression of coronary atherosclerosis in a year. RESULTS: Data analysis shall begin following the conclusion of the trial with results to follow. CONCLUSION: Ketogenic diets have generated debate and raised concerns within the medical community, especially in the subset exhibiting immense elevations in LDL-C, who interestingly are lean and healthy. The relationship between elevated LDL-C and ASCVD progression in this population will provide better insight into the effects of diet-induced hypercholesterolemia.

Lack of effect of an in-line filter on cardiopulmonary exercise testing variables in healthy subjects.

PURPOSE: Pathogen transmission during cardio-pulmonary exercise testing (CPET) is caused by carrier aerosols generated during respiration. METHODS: Ten healthy volunteers (age range: 34 ± 15; 4 females) were recruited to see if the physiological reactions to ramp-incremental CPET on a cycle ergometer were affected using an in-line filter placed between the mouthpiece and the flow sensor. The tests were in random order with or without an in-line bacterial/viral spirometer filter. The work rate aligned, time interpolated 10 s bin data were compared throughout the exercise period. RESULTS: From rest to peak exercise, filter use increased only minute ventilation ([Formula: see text]E) (Δ[Formula: see text]E = 1.56 ± 0.70 L/min, P < 0.001) and tidal volume (VT) (ΔVT = 0.10 ± 0.11 L, P = 0.014). Over the entire test, the slope of the residuals for [Formula: see text]CO2 was positive (0.035 ± 0.041 (ΔL/L), P = 0.027). During a ramp-incremental CPET in healthy subjects, an in-line filter increased [Formula: see text]E and VT but not metabolic rate. CONCLUSION: In conclusion, using an in-line filter is feasible, does not affect appreciably the physiological variables, and may mitigate risk of aerosol dispersion during CPET.

Association between coronary artery calcium and thoracic spine bone mineral density: Multiethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Previously, osteoporosis and coronary artery disease were considered unrelated. However, beyond age, these two conditions appear to share common etiologies that are not yet fully understood. We examined the relationship between thoracic spine bone mineral density (BMD) and severity of coronary artery calcium (CAC) score. METHODS AND RESULTS: MESA is a prospective cohort study of 6814 men and women between the ages of 45 and 84 years, without clinical cardiovascular disease. This study included participants who underwent non-contrast chest CT scans to determine CAC score and thoracic spine BMD. The thoracic spine BMD was categorized into osteoporosis (defined as T score: ≤ -2.5), osteopenia (T-score between: -2.5 and -1) and normal BMD (T-score ≥ -1). There were 3392 subjects who had CAC >0 at baseline. The prevalence of CAC >0 was 36% in normal BMD group, 49% in the osteopenia and 68% in osteoporosis group. After adjusting for risk factors of atherosclerosis, in multivariate regression models we found a significant association between CAC and osteoporosis (OR: 1.40, 95% CI 1.16-1.69, p value < 0.0004). Furthermore, we stratified our results by gender and found a statistically significant association in both men and women. CONCLUSION: Results from this cross-sectional analysis of a large population based ethnically diverse cohort indicate a significant inverse relationship between thoracic BMD and CAC in both genders independent of other cardiovascular risk factors. Future studies need to explore the underlying pathophysiological mechanisms relating BMD and coronary artery calcification.

Obstructive coronary artery disease in symptomatic diabetics with zero coronary calcium score: are we missing something?

BACKGROUND: Prevalence and severity of coronary artery disease (CAD) in symptomatic patients with zero coronary artery calcium score (CACS) are unclear, particularly in regard to the diabetic population, which represents, per se, a subgroup at increased cardiovascular risk. The aim of this study was to investigate the prevalence and severity of CAD by coronary computed tomography angiography (CCTA) in a symptomatic diabetic cohort with zero CACS. METHODS: All consecutive symptomatic diabetics referred for CAD suspicion were included in this study. All subjects underwent a noncontrast coronary artery calcium scan followed by CCTA. CACS was quantified using the Agatston method. CAD was defined as a total plaque score (TPS) greater than zero. Obstructive and severe obstructive CAD were defined respectively as luminal stenosis >50% and >70% in at least one coronary segment. RESULTS: We identified 1722 symptomatic diabetics (mean age 62.5 ± 12.9 years, 62% men). One hundred and eleven subjects had zero CACS and TPS >0 (mean age was 49.5 ± 14.8, 58% women, 56% Hispanics). Sixty-five patients (58.5%) had one-vessel disease, followed by 30 (27%) with two-vessel disease and 14 (12.6%) with ≥ three-vessel disease. Obstructive CAD was found in 11 subjects and, among these, three were categorized as severe obstructive CAD. CONCLUSION: In symptomatic diabetic patients with zero CACS, CAD, including obstructive disease, can still occur and is predominant in middle-aged adults, women and Hispanics. In symptomatic diabetics CCTA is a critical step for accurate risk stratification even when CACS would have placed some of these individuals in a lower-risk category.

Coronary computed tomography angiography evaluation of plaque morphology and its relationship to HDL and total cholesterol to HDL ratio.

BACKGROUND: While population studies have demonstrated that high density lipoprotein cholesterol (HDL-C) and the ratio of total cholesterol to HDL (TC/HDL) improve cardiovascular risk prediction, the mechanism by which these parameters protect the cardiovascular system remains uncertain. OBJECTIVE: To investigate the relationship between the HDL-C level and the total cholesterol to HDL (TC/HDL) ratio with the morphology of coronary artery plaque as determined by coronary computed tomography angiography (CCTA). METHODS: This is a cross-sectional study involving 190 subjects with stable coronary artery disease. Semi-automated plaque analysis software was utilized to quantify plaque and plaque volumes are presented as total atheroma volume normalized (TAVnorm). Multivariate regression models were used to evaluate the association of HDL-C and TC/HDL ratio with coronary plaque volumes. RESULTS: Of the 190 subjects the average (SD) age was 58.9 (9.8) years, with 63% being male. After adjustment for cardiovascular risk factors, HDL- C (>40 mg/dl) is inversely associated with fibrous (p = 0.003), fibrous fatty (p = 0.007), low attenuation plaque (LAP) (p = 0.007), total non-calcified plaque (TNCP) (p = 0.002) and total plaque (TP)(p = 0.004) volume. Furthermore, the TC/HDL ratio (> 4.0) is associated with fibrous (p = 0.047) and total non-calcified plaque (p = 0.039), but not with fibrofatty, LAP, dense calcified plaque, or TP volume. CONCLUSION: There is a strong association between low HDL-C levels and increasing TC/HDL ratio with certain types of coronary plaque characteristics, independent of traditional risk factors. The findings of this study suggest mechanistic evidence supporting the protective role of HDL-C and the TC/HDL ratio's clinical relevance in coronary artery disease management.

Assessment of left main coronary artery disease: a comparison between invasive and noninvasive.

Left main coronary artery disease has significant therapeutic as well as prognostic implications. The presence of left main coronary artery stenosis is strongly associated with poor short- and long-term prognoses. Accurate identification of left main stenosis is extremely important since it would be the main factor to guide management. There are several modalities used to determine the presence of atherosclerosis and the degree of stenosis in a left main coronary artery. Newer modalities allow for an accurate evaluation of left main stenosis and atherosclerosis. In this review, we go through different invasive and noninvasive modalities to diagnose left main stenosis, shedding more light into coronary computed tomography angiography, and its accuracy in this specific diagnosis.

Relationship between genomic risk scores (GRS) and coronary artery calcium (CAC) score: A pilot study.

BACKGROUND: Coronary artery disease (CAD) genomic risk scores (GRS), as FDR202, GRS46K, 1.7M, and MetaGRS, help in assessing cardiovascular related morbidity and mortality. Interventions to adhere to a healthy lifestyle as a means of prevention based on the GRS have a potential to greatly reduce incident CAD event rates. We performed a prospective observational study to see the relationship between GRS and coronary artery calcium (CAC) scoring in individuals who are at risk. METHODS: 104 subjects with mean age 55.1 ± 8.8 years were enrolled and consented and all the participants underwent CAC scoring. 55 (53%) were male. CAC score was measured using the Agatston method. Spearman correlation analysis assessed relationships between GRS scores and CAC scores, in the entire sample and in subjects with CAC score greater than zero. Multivariable linear regression analyzed associations while adjusting potential confounding variables. RESULTS: Mean ± SD CAC score of the study population was 49.0 ± 130. A significant negative correlation was noted between FDR202 Prevalence and total CAC Score in 39 subjects with CAC >0, r = -0.35, p = 0.02. Multivariable analysis shows a significant association between FDR202 prevalence and log adjusted CAC score in subjects with CAC >0 while adjusting age, gender, hypertension and hyperlipidemia (ß = -0.2, SE = 0.1, p = 0.04). No significant correlations were found between GRS46K, 1.7M, and MetaGRS with CAC score. CONCLUSION: Additional research is necessary in a larger population to evaluate the potential role of GRS for the detection of CAD. This allows the individuals to adopt a healthy lifestyle modification to minimize the cardiovascular risk and delays the onset of most diseases of old age to prolong the life.

Coronary artery plaque progression and cardiovascular risk scores in men with and without HIV-infection.

OBJECTIVE: The aim of this study was to assess the association of cardiovascular disease (CVD) risk scores and coronary artery plaque (CAP) progression in HIV-infected participants. METHODS: We studied men with and without HIV-infection enrolled in the Multicenter AIDS Cohort Study (MACS) CVD study. CAP at baseline and follow-up was assessed with cardiac computed tomography angiography (CCTA). We examined the association between baseline risk scores including pooled cohort equation (PCE), Framingham risk score (FRS), and Data collect of Adverse effects of anti-HIV drugs equation (D:A:D) and CAP progression. RESULTS: We studied 495 men (211 HIV-uninfected, 284 HIV-infected). The adjusted odds ratio (aOR) of total plaque volume (TPV) and noncalcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 9.4 [95% confidence interval (95% CI) 2.4-12.1, P < 0.001)] and 7.7 (95% CI 3.1-19.1, P < 0.001) times greater, respectively, among HIV-uninfected men in the PCE atherosclerotic cardiovascular disease (ASCVD) high vs. low-risk category. Among HIV-infected men, the association for TPV and NCPV progression for the same PCE risk categories, odds ratio (OR) 2.8 (95% CI 1.4-5.8, P < 0.01) and OR 2.4 (95% CI 1.2-4.8, P < 0.05), respectively (P values for interaction by HIV = 0.02 and 0.08, respectively). Similar results were seen for the FRS risk scores. Among HIV-uninfected men, PCE high risk category identified the highest proportion of men with plaque progression in the highest tertile, although in HIV-infected men, high-risk category by D:A:D identified the greatest percentage of men with plaque progression albeit with lower specificity than FRS and PCE. CONCLUSION: PCE and FRS categories predict CAP progression better in HIV-uninfected than in HIV-infected men. Improved CVD risk scores are needed to identify high-risk HIV-infected men for more aggressive CVD risk prevention strategies.

COVID-19 IgG/IgM antibody testing in Los Angeles County, California.

Evidence suggests that asymptomatic and mild SARS-CoV-2 infections comprise > 95% of all cases. Developing a test that indicates past infection and possible immunity against the virus is important. We administered 244 antibody tests to three groups of high-risk population. The test consisted of an IgG component and an IgM component. The overall IgM/IgG positivity for patients with none, mild, moderate, and severe symptoms were 21.1%, 21.8%, 14.2%, and 26.9%, respectively. Those with moderate or severe symptoms were no more or less likely to have positive antibody tests than those with no or mild symptoms.

Association of Aspirin and Other Nonsteroidal Anti-inflammatory Drugs With Vertebral Trabecular Bone: Data From Multiethnic Study of Atherosclerosis, a Population-Based Multicenter Cohort Study.

OBJECTIVE: The objective of this article was to study the association of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with bone mineral density (BMD). METHODS: Spine BMD was evaluated in a subset of 2028 participants from the Multiethnic Study of Atherosclerosis cohort who were NSAID users (including aspirin) and underwent both lumbar and thoracic imaging. Multiethnic Study of Atherosclerosis is a prospective cohort study that includes 4 ethnic groups (white, Asian, African American, and Hispanic). Trabecular BMD was evaluated by quantitative computed tomography based on cardiac computed tomography images, which were obtained during coronary calcium scans. The analyses were cross sectional using baseline examination data for exposure and outcomes. RESULTS: After adjustment for potential confounders including age, sex, race, and traditional cardiovascular risk factors, a small association between trabecular BMD and baseline use of COX-2-selective NSAID was observed. COX-2-selective NSAID use was associated with 7.4 mg/cm (95% confidence interval [CI], 1.6-13.3; P = 0. 013) higher trabecular BMD in thoracic spine and 10.6 mg/cm higher at lumbar spine (95% CI, 5.1-16.1; P < 0.001). Among regular aspirin users, there was no association between drug use and trabecular BMD. Considering all spine fractures together, the prevalence ratio of fractures among aspirin users was 1.0 (95% CI, 0.6-1.6) and 1.1 (95% CI, 0.5-2.3) among COX-2-selective NSAID users. CONCLUSIONS: Regular use of aspirin has no significant association with trabecular BMD in either the thoracic or lumbar spine and no association with fracture prevalence. COX-2-selective NSAIDs may have modest positive association with BMD, but the mechanisms were not assessed and the observational study design makes residual confounding a possible alternate explanation. Potential pathological mechanisms warrant further longitudinal exploration.

20-Year trend of high prevalence of zero coronary artery calcium in beach cities of Southern California: A blue zone?

BACKGROUND: Blue zones are longevity hotspots around the world characterized by highest concentrations of healthy centenarians. Certified blue zone communities are designed by implementation of environmental and policy changes that promote healthy behaviors. OBJECTIVE: To examine the trends of prevalence of zero CAC, a marker of ideal cardiovascular and overall health status and burden of cardiovascular risk factors in Beach Cities/certified blue zones of Southern California and rest of California. METHODS: This is a population-based cohort study of persons aged 50 years or older in California, who underwent CAC screening between 2000 and 2019. A total of 3864 participants from Beach Cities of Southern California were identified by Zip Codes and compared with 35,537 participants from rest of California. We compared trends of prevalence of zero CAC and cardiovascular risk factors between the two groups, in 5-year intervals. RESULTS: Among 39,401 participants (mean age, 58.1 years; 36% women), 13,374 (34%) had zero CAC. The prevalence of CAC â€‹= â€‹0 was significantly higher in Beach Cities compared to the rest of California (p â€‹< â€‹0.001). Across the study period, the prevalence of cardiac risk factors including obesity, smoking, diabetes and hypertension remain significantly lower in Beach Cities. (p â€‹< â€‹0.001). CONCLUSIONS: This study, shows for the first time, that higher prevalence of zero CAC in Beach Cities of California, adds validity to excellent prognosis and longevity in these areas. The impact of policy implementation and environmental changes on lifestyle patterns, cardiovascular health and healthy ageing needs to be evaluated.

Low short-term and long-term cardiovascular and all-cause mortality in absence of coronary artery calcium: A 22-year follow-up observational study from large cohort.

OBJECTIVES: We sought to evaluate the gender-specific predictive value of coronary artery calcium (CAC) score on all-cause mortality and cardiovascular disease (CVD) mortality in individuals with and without diabetes mellitus (DM). BACKGROUND: CAC score is a robust predictor of CVD and all-cause mortality during long-term follow-up in large cohorts in adults with DM. However, less is known about its sex-specific impact on all-cause mortality in DM. METHODS: We evaluated 25,563 asymptomatic participants with no known history of coronary artery disease (CAD) who underwent clinically indicated CAC. 1999 (7.8%) individuals had diabetes. CAC was characterized as an Agatston score of 0, 1-99, 100-300, and ≫300. We evaluated the association between CAC and all-cause mortality and CVD mortality. RESULTS: Overall, 1345 individuals died (5.3%) from all causes during a mean follow-up of 14.7 ±â€¯3.8 years. CAC score was 0 in 57.5% females and 34.4% of males without DM, while 36.6% females and 20.3% males with DM had CAC-0. The frequency of CAC ≫ 300 was 18% and 36% in females and males with DM, respectively. CAC score of zero was associated with low all-cause mortality event rate in females and males with diabetes (1.7 and 2.5 events per 1000 person-years, respectively). Cardiovascular mortality per 1000 person years was ≪1 in females and males with CAC score of 0 irrespective of their diabetes. Adjusted multivariable analysis, compared to CAC-0, HR for all-cause mortality associated with CAC 1-99, 100-299 and ≫300 were 1.74(95% CI 0.65, 4.63, P-0.20), 5.54(95% CI 2.16, 14.22, P ≪ 0.001) and 5.75(95% CI 2.30, 14.37, P ≪ 0.001) in females with DM respectively; in males with DM HR associated with CAC 1-99, 100-299 and ≫300 were 1.87(95% CI 0.95, 3.66, P-0.06), 2.15(95% CI 1.05, 4.38, P-0.035) and 2.60(95% CI 1.34, 5.0, P-0.004), respectively. CONCLUSION: Presence of subclinical atherosclerosis varies among individuals with DM. The absence of CAC was associated with very low cardiovascular as well as all-cause mortality events in all subgroups during long term follow-up.