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Background and Aims:Olive oil consumption is associated with lower cardiovascular disease (CVD) risk. We recently demonstrated that frequent olive oil consumption was inversely associated with thrombin-induced platelet activation ex vivo. While various olive oil phenolic compounds, notably hydroxytyrosol, have been shown to reduce human platelet aggregation ex vivo, little is known about how olive oil affects platelet activation, a key mediator of atherothrombosis. Therefore, we sought to investigate whether hydroxytyrosol exposure affects platelet activation.Methods and Results:Ten healthy, non-smoking men and women (25.0±1.6 years) with normal body mass index (BMI 22.2±3.3 kg/m2) were recruited for ex vivoplatelet studies. Individuals on antiplatelet or anticoagulation medications or medications known to influence lipid levels were excluded. Subjects attended a single visit at NYU Langone where platelet-rich plasma (PRP) was isolated and incubated with three different concentrations of hydroxytyrosol or ethanol vehicle for 60 minutes at room temperature. PRP was then incubated with bovine thrombin for 5 minutes followed by anti-CD62P for 15 minutes in the dark. Platelet activation was determined by platelet surface expression of P-selectin, assessed via flow cytometry. Ex vivoexposure to hydroxytyrosol inhibited thrombin-induced platelet P-selectin expression in a dose-dependent manner (Figure).Conclusions:We demonstrate that hydroxytyrosol exposure reduces thrombin-induced platelet P-selectin expression in a dose-response fashion. The dose response seen in this ex vivoplatelet activation study is consistent with our clinical observation that more frequent olive oil intake was associated with reduced ex vivothrombin-induced P-selectin expression. This laboratory study suggests a putative mechanism underlying our clinical observation as well as the established inverse association of olive oil consumption with CVD.

Background:Randomized clinical trials (RCTs) investigating the impact of omega-3-fatty acid supplementation on cardiovascular events have largely shown no benefit. A recent RCT suggested benefit from an eicosapentaenoic acid (EPA)-only supplement. However, there is debate about the benign nature of the placebo in this trial.Methods:MEDLINE and EMBASE were searched through May, 2021 to identify RCTs that investigated cardiovascular outcomes with omega-3-fatty acid formulations (EPA, decosahexanoic acid (DHA) or the combination) versus placebo or standard care of controls. Outcomes of interest were cardiovascular death, myocardial infarction, stroke, coronary revascularization, and all-cause death.Results:Our analysis included 17 RCTs that enrolled a total of 141,009 patients randomized to EPA (n =13,655), EPA+DHA (n =56,908), mineral oil placebo (n =5,338), corn oil placebo (n =8,876), olive oil placebo (n =41,009) and controls (no placebo oil; n =15,223). Rates of cardiovascular death, myocardial infarction and stroke were significantly lower in those receiving EPA compared to those receiving mineral oil, but were not different from rates in those receiving other oils or standard of care controls. Rates of coronary revascularization were significantly lower in those receiving EPA than in those receiving either EPA+DHA, mineral oil, corn oil, or olive oil placebo, but not standard of care controls. All-cause death was similar among all groups.Conclusion:Our analyses demonstrate that although EPA supplementation lowers risk of coronary revascularization more than other oils, there is no benefit relative to standard of care. Further, EPA reduces the risk of cardiovascular events only in comparison to mineral oil and not when compared with other placebo oils or to standard of care. Any benefit of EPA-only supplementation in improving cardiovascular outcomes is not currently generalizable outside of select studies incorporating mineral oil placebo.

Background:Physical activity (PA) can protect against cardiovascular disease but it is not routinely assessed in clinical settings. The current PA recommendations are 150 minutes of moderate- or 75 minutes vigorous-intensity PA/week.Purpose:The purpose of this study was to implement physical activity screening as part of the electronic kiosk check-in process in an adult preventive cardiology clinic in an academic medical center and assess factors related to patients’ self-reported PA.Methods:The physical activity vital sign (PAVS) was embedded into the Epic electronic health record and includes 3 questions about the average days, minutes and intensity (light, moderate, vigorous) of PA per week. Analysis of patient records from a recent 60-day period included descriptive statistics, bivariate analyses and logistic regression to identify sociodemographic factors associated with not meeting current PA recommendations.Results:A total of 1,322 patients checked into the clinic using a kiosk. Patients were 42% female, 71% White, 62% married, had a mean age 64±15 years, 41% worked full-time and the majority (57%) were never smokers. The three most common primary diagnoses were hyperlipidemia (n=197), coronary artery disease (n=189), and hypertension (n=127). Of those patients, 72% (n=951) completed the PAVS questions:10% reported no PA; 55% reported some PA; and 35% reported achieving at least 150 minutes moderate or 75 minutes vigorous PA/week. In bivariate analyses (at recommended PA vs. not at recommended PA), factors associated with not achieving recommended levels of PA included sex (p<.001), race (p=.045), marital status (p<.001), and employment (p<.001). In the final logistic model, being female vs. male (OR=1.4, 95%CI: 0.99-1.8, p=.05), Black (OR=2.0, 95%CI: 1-3.7, p=.037) or ‘Other’ race (OR=1.5, 95%CI: 1-2.2, p=.04) vs. White, those reporting being partnered or in ‘other’ relationships vs. married (OR=.03, 95% CI: 0.14-0.55, p<.001), and those who were retired (OR=2, 95% CI: 1.4-2.8, p<.001) or unemployed (OR=2.2, 95%CI: 1.3-3.7, p=.002) vs. full-time workers were factors associated with not achieving recommended levels of PA.Conclusion:In a preventive cardiology clinic, only one-third reported achieving AHA recommended levels of PA. Our data support particular attention to PA counseling and prescription in female, Black, and retired or unemployed patients. Additionally, embedding the PAVS into a clinical electronic health system is a feasible and scalable intervention to collect data on this cardiovascular risk factor.

Patients with severe PAD undergoing lower extremity revascularization (LER) remain at increased risk for future cardiovascular events beyond the early post-operative period. Identifying those who are at elevated risk for major adverse cardiovascular events (MACE) is of critical importance. We recently showed that LDL aggregates increase MMP7 secretion from foam cells. Further, in patients with CAD, the presence of aggregation-prone LDL is predictive of future cardiovascular death independent of conventional risk factors. Whether LDL aggregation is predictive of future events in PAD is unknown. 239 patients undergoing LER were prospectively enrolled, studied preoperatively, and followed for future events. MACE were adjudicated by a blinded, independent clinical event adjudication committee. LDL was isolated from pre-operative blood samples by sequential ultracentrifugation. LDL aggregation was induced by human recombinant acidic sphingomyelinase and aggregate size was measured by dynamic light scattering for four hours. LDL aggregation was increased in PAD subjects (72.1 ? 11.1 years, 32.6% female, 62.3% white) compared to 20 age, sex and race-matched controls (p<0.001; median aggregate size at 1 hour ? 1600 and 380 nm, respectively). LDL-C did not correlate with LDL aggregation (r=-0.03). Over median follow-up of 18 months, 63/239 subjects experienced MACE. Pre-operative LDL-C did not differ in those subjects who did and did not experience MACE (71?28 vs 70?23 mg/dL), whereas LDL aggregation was increased in those experiencing MACE (p=0.01). Specifically, patients in the highest tertile of LDL aggregation experienced nearly double the event rate (38%) of the lower two tertiles (20.6%, p=0.009). Pre-operative LDL aggregation remained predictive of MACE (p=0.02) after correcting for age, sex, ethnicity, BMI, smoking, hypertension, hyperlipidemia, diabetes, CAD, prior MI, statin use, and LDL-C. Our data suggest that LDL aggregation is an independent marker of risk for MACE in patients undergoing LER. In combination with prior data in CAD patients, the potential of LDL aggregation as a useful clinical risk marker is emerging. Prospective outcome studies of interventions to reduce LDL aggregation in patients at high risk of MACE are warranted.

Lipoprotein insulin resistance (LPIR) is a composite biomarker representative of atherogenic dyslipidemia characteristic of early insulin resistance. Clinically, it is elevated in obesity and may provide information not captured in HbA1c and HOMA-IR. Although bariatric surgery is the most effective intervention for severe obesity, reduces diabetes incidence, and resolves the metabolic syndrome, the effect of bariatric surgery on LPIR is untested. We sought to assess the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on LPIR in severely obese, non-diabetic women.Anthropometric measures and blood sampling were performed preoperatively and at six, and 12 months postoperatively. LPIR was measured by NMR spectroscopy.Among 53 women (RYGB, n=22; SG, n=31), mean age was 32?7 years and BMI 44.1?6.4 kg/m2. LPIR was reduced by 35?4% and 46?4% at six and 12 months after surgery, respectively, with no difference by surgical procedure. 27 of 53 subjects met IDF criteria for the metabolic syndrome prior to surgery and exhibited higher HOMA-IR, HbA1c, nonHDL-C and LPIR preoperatively. Twenty-five of 27 subjects experienced resolution of the metabolic syndrome diagnosis postoperatively. Concordantly, the preoperative differences in HOMA-IR, HbA1c and nonHDL-C between those with and without metabolic syndrome resolved at six and 12 months. In contrast, subjects with the metabolic syndrome prior to surgery show persistent elevated LPIR scores at six and 12 months post-operatively, suggestive of potentially unappreciated residual dyslipidemic risk.We are the first to show improvement in insulin resistance, as measured by LPIR, following bariatric surgery. We also show that this measure discriminates those with a preoperative metabolic syndrome diagnosis at up to one year post-operatively. Larger prospective studies are needed to determine the additive value of LPIR in characterizing cardiometabolic risk in severely obese patients.