Eicosapentaenoic and docosahexaenoic acid supplementation and coronary artery calcium progression in patients with coronary artery disease: A secondary analysis of a randomized trial.

BACKGROUND AND AIMS: We previously reported that an omega-3 fatty acid index ≥4% with high-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) prevented progression of noncalcified plaque. Higher coronary artery calcium (CAC) scores and progression of CAC are associated with increased cardiovascular events and mortality. We examined the effect of EPA + DHA on CAC score. METHODS: A total of 242 patients with coronary artery disease (CAD) on statin therapy were randomized to 1.86 g EPA and 1.5 g DHA daily or none (control) for 30 months. The CAC score was measured at baseline and 30-months with non-contrast, cardiac computed tomography. RESULTS: Both EPA + DHA and control groups had significant progression in CAC scores over 30 months (median change:183.5 vs 221.0, respectively, p < 0.001) despite a 13.6% reduction in triglyceride level with EPA + DHA. No significant difference was observed between groups for the total group, by baseline CAC scores of <100, 100-399, 400-999 and ≥1000 or quartiles of achieved levels of EPA, DHA and the omega-3 fatty acid index. Similar rates of CAC progression were noted in those on high-intensity statin compared to low- and moderate-intensity statin. CONCLUSIONS: EPA and DHA added to statin resulted in similar CAC progression over 30 months regardless of baseline CAC categories, statin intensity and achieved levels of EPA, DHA and the omega-3 fatty acid index.

Frequency of Use and Outcomes of Colonoscopy in Individuals Older Than 75 Years.

Importance: The benefits from colorectal cancer (CRC) screening may take 10 to 15 years to accrue. Therefore, screening is recommended for older adults who are in good health. Objective: To determine the number of screening colonoscopies done in patients older than 75 years with a life expectancy of fewer than 10 years, diagnostic yield, and associated adverse events within 10 days and 30 days of the procedure. Design: This cross-sectional study with a nested cohort between January 2009 and January 2022 in an integrated health system assessed asymptomatic patients older than 75 years who underwent screening colonoscopy in the outpatient setting. Reports with incomplete data, any indication other than screening, patients who had a colonoscopy within the previous 5 years, and patients with a personal history of inflammatory bowel disease or CRC were excluded. Exposures: Life expectancy based on a prediction model from previous literature. Main Outcomes and Measures: The primary outcome was the percentage of screened patients who had limited (<10 years) life expectancy. Other outcomes included colonoscopy findings and adverse events that developed within 10 days and 30 days of the procedure. Results: A total of 7067 patients older than 75 years were included. The median (IQR) age was 78 (77-79) years, 3967 (56%) were women, and 5431 (77%) were White with an average of 2 comorbidities (taken from a select group of comorbidities). The proportion of colonoscopies performed on patients with a life expectancy of fewer than 10 years aged 76 to 80 years was 30% in both sexes and increased with age-82% of men and 61% of women aged 81 to 85 years (71% total), and 100% of patients beyond the age of 85 years. Adverse events requiring hospitalizations were common at 10 days (13.58 per 1000) and increased with age, particularly among patients older than 85 years. The detection of advanced neoplasia varied from 5.4% among patients aged 76 to 80 years to 6.2% in those aged 81 to 85 years and 9.5% among patients older than 85 years (P = .02). Of the total population, 15 patients (0.2%) had invasive adenocarcinoma; among patients with a life expectancy of fewer than 10 years, 1 of 9 was treated, whereas 4 of 6 patients with a life expectancy of greater than or equal to 10 years were treated. Conclusions and Relevance: In this cross-sectional study with a nested cohort, most screening colonoscopies performed in patients older than 75 years were in patients with limited life expectancy and associated with increased risk of complications. Colorectal cancer was exceedingly rare.

Supplemental calcium and vitamin D and long-term mortality in aortic stenosis.

OBJECTIVE: Calcium metabolism has long been implicated in aortic stenosis (AS). Studies assessing the long-term safety of oral calcium and/or vitamin D in AS are scarce yet imperative given the rising use among an elderly population prone to deficiency. We sought to identify the associations between supplemental calcium and vitamin D with mortality and progression of AS. METHODS: In this retrospective longitudinal study, patients aged ≥60 years with mild-moderate native AS were selected from the Cleveland Clinic Echocardiography Database from 2008 to 2016 and followed until 2018. Groups were stratified into no supplementation, supplementation with vitamin D alone and supplementation with calcium±vitamin D. The primary outcomes were mortality (all-cause, cardiovascular (CV) and non-CV) and aortic valve replacement (AVR), and the secondary outcome was AS progression by aortic valve area and peak/mean gradients. RESULTS: Of 2657 patients (mean age 74 years, 42% women) followed over a median duration of 69 months, 1292 (49%) did not supplement, 332 (12%) took vitamin D alone and 1033 (39%) supplemented with calcium±vitamin D. Calcium±vitamin D supplementation was associated with a significantly higher risk of all-cause mortality (absolute rate (AR)=43.0/1000 person-years; HR=1.31, 95% CI (1.07 to 1.62); p=0.009), CV mortality (AR=13.7/1000 person-years; HR=2.0, 95% CI (1.31 to 3.07); p=0.001) and AVR (AR=88.2/1000 person-years; HR=1.48, 95% CI (1.24 to 1.78); p<0.001). Any supplementation was not associated with longitudinal change in AS parameters in a linear mixed-effects model. CONCLUSIONS: Supplemental calcium with or without vitamin D is associated with lower survival and greater AVR in elderly patients with mild-moderate AS.

Vitamin K2-a neglected player in cardiovascular health: a narrative review.

Vitamin K2 serves an important role in cardiovascular health through regulation of calcium homeostasis. Its effects on the cardiovascular system are mediated through activation of the anti-calcific protein known as matrix Gla protein. In its inactive form, this protein is associated with various markers of cardiovascular disease including increased arterial stiffness, vascular and valvular calcification, insulin resistance and heart failure indices which ultimately increase cardiovascular mortality. Supplementation of vitamin K2 has been strongly associated with improved cardiovascular outcomes through its modification of systemic calcification and arterial stiffness. Although its direct effects on delaying the progression of vascular and valvular calcification is currently the subject of multiple randomised clinical trials, prior reports suggest potential improved survival among cardiac patients with vitamin K2 supplementation. Strengthened by its affordability and Food and Drug Adminstration (FDA)-proven safety, vitamin K2 supplementation is a viable and promising option to improve cardiovascular outcomes.

Vitamin K2 supplementation and arterial stiffness among renal transplant recipients-a single-arm, single-center clinical trial.

Subclinical vitamin K deficiency is prevalent among renal transplant recipients and is associated with an increased risk of cardiovascular disease. However, the association between vitamin K supplementation and improvement of arterial stiffness has not been explored in the renal transplant population. The KING trial (vitamin K2 In reNal Graft) is a single-arm study that evaluated the association between the change in vitamin K status and indices of arterial stiffness following 8 weeks of menaquinone-7 (vitamin K2) supplementation (360 µg once daily) among renal transplant recipients (n = 60). Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Subclinical vitamin K deficiency was defined as plasma concentration of dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.At baseline, 53.3% of the study subjects had subclinical vitamin K deficiency. Supplementation was associated with a 14.2% reduction in mean cfPWV at 8 weeks (cfPWV pre-vitamin K2 = 9.8 ± 2.2 m/s vs. cfPWV post-vitamin K2 = 8.4 ± 1.5 m/s; P < .001). Mean dp-ucMGP concentrations were also significantly reduced by 55.1% following menaquinone-7 supplementation with a reduction in the prevalence of subclinical deficiency by 40% (P = .001). When controlled for age, durations of hemodialysis and transplantation, and the change in 24-hour mean arterial pressure, the improvement in arterial stiffness was independently associated with the reduction in dp-ucMGP concentration (P = .014).Among renal transplant recipients with stable graft function, vitamin K2 supplementation was associated with improvement in subclinical vitamin K deficiency and arterial stiffness. (Clinicaltrials.gov: NCT02517580).

ß-2-himachalen-6-ol: A novel anticancer sesquiterpene unique to the Lebanese wild carrot.

Daucus carota ssp. carota, also known as wild carrot, is a commonly used herb in Lebanese folk medicine to treat several ailments including cancer. Previous studies in our laboratories showed that the Daucus carota oil extract (DCOE) and subsequent fractions exhibit antioxidant, anti-inflammatory and anti-cancer activities. In this study, we report the isolation and identification of the major compound responsible for the anti-cancer activity of DCOE along with the mechanism of action involved. GC-MS and NMR spectroscopy revealed the identity of the major compound as ß-2-himachalen-6-ol, a novel sesquiterpene unique to the Lebanese wild carrot. ß-2-Himachalen-6-ol demonstrated potent anti-cancer activity against B16F-10, Caco-2, MB-MDA-231, A549 and SF-268 cancer cells (IC50 13-4µg/ml; 58-18µM), with SF-268 cells being the most sensitive. The sesquiterpene was shown to induce cell death through apoptosis (flow cytometry), decrease 2D cell motility (wound healing assay) and 3D invasion, as well as increase cell adhesion in SF-268 cells. Additionally, ß-2-himachalen-6-ol showed very low toxicity in mice with an LD50>6000mg/kg body weight. In conclusion, the present data demonstrate that ß-2-himachalen-6-ol is a potential multi-mechanistic chemotherapeutic drug with high potency and safety.

Efficient and cost-effective alternative treatment for recurrent urinary tract infections and interstitial cystitis in women: a two-case report.

Urinary tract infections (UTIs) are among the most common bacterial infections affecting women. UTIs are primarily caused by Escherichia coli, which increases the likelihood of a recurrent infection. We encountered two cases of recurrent UTIs (rUTIs) with a positive E. coli culture, not improving with antibiotics due to the development of antibiotic resistance. An alternative therapeutic regimen based on parsley and garlic, L-arginine, probiotics, and cranberry tablets has been given. This regimen showed a significant health improvement and symptoms relief without recurrence for more than 12 months. In conclusion, the case supports the concept of using alternative medicine in treating rUTI and as a prophylaxis or in patients who had developed antibiotic resistance.