Long-term cardiovascular risks and the impact of statin treatment on socioeconomic inequalities: a microsimulation model.

BACKGROUND: UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist. AIM: To present a new CVD model, and project health outcomes and the impact of guideline-recommended statin treatment across quintiles of socioeconomic deprivation in the UK. DESIGN AND SETTING: A lifetime microsimulation model was developed using 117 896 participants in 16 statin trials, 501 854 UK Biobank (UKB) participants, and quality-of-life data from national health surveys. METHOD: A CVD microsimulation model was developed using risk equations for myocardial infarction, stroke, coronary revascularisation, cancer, and vascular and non-vascular death, estimated using trial data. The authors calibrated and further developed this model in the UKB cohort, including further characteristics and a diabetes risk equation, and validated the model in UKB and Whitehall II cohorts. The model was used to predict CVD incidence, life expectancy, quality-adjusted life years (QALYs), and the impact of UK guideline-recommended statin treatment across socioeconomic deprivation quintiles. RESULTS: Age, sex, socioeconomic deprivation, smoking, hypertension, diabetes, and cardiovascular events were key CVD risk determinants. Model-predicted event rates corresponded well to observed rates across participant categories. The model projected strong gradients in remaining life expectancy, with 4-5-year (5-8 QALYs) gaps between the least and most socioeconomically deprived quintiles. Guideline-recommended statin treatment was projected to increase QALYs, with larger gains in quintiles of higher deprivation. CONCLUSION: The study demonstrated the potential of guideline-recommended statin treatment to reduce socioeconomic inequalities. This CVD model is a novel resource for individualised long-term projections of health outcomes of CVD treatments.

Low-Dose Methotrexate for the Prevention of Atherosclerotic Events.

BACKGROUND: Inflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1ß, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition with low-dose methotrexate might provide similar benefit. METHODS: We conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo in 4786 patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome. All participants received 1 mg of folate daily. The primary end point at the onset of the trial was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Near the conclusion of the trial, but before unblinding, hospitalization for unstable angina that led to urgent revascularization was added to the primary end point. RESULTS: The trial was stopped after a median follow-up of 2.3 years. Methotrexate did not result in lower interleukin-1ß, interleukin-6, or C-reactive protein levels than placebo. The final primary end point occurred in 201 patients in the methotrexate group and in 207 in the placebo group (incidence rate, 4.13 vs. 4.31 per 100 person-years; hazard ratio, 0.96; 95% confidence interval [CI], 0.79 to 1.16). The original primary end point occurred in 170 patients in the methotrexate group and in 167 in the placebo group (incidence rate, 3.46 vs. 3.43 per 100 person-years; hazard ratio, 1.01; 95% CI, 0.82 to 1.25). Methotrexate was associated with elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non-basal-cell skin cancers than placebo. CONCLUSIONS: Among patients with stable atherosclerosis, low-dose methotrexate did not reduce levels of interleukin-1ß, interleukin-6, or C-reactive protein and did not result in fewer cardiovascular events than placebo. (Funded by the National Heart, Lung, and Blood Institute; CIRT ClinicalTrials.gov number, NCT01594333.).

Fundamentals for an Osteopathic Obesity Designed Study: The Effects of Education on Osteopathic Medical Students' Attitudes Regarding Obesity.

CONTEXT: Obesity is a major health concern in the United States, and its prevalence continues to rise. Although it is a common health issue, many people, including health care professionals, are biased against people with obesity. OBJECTIVE: To determine whether a comprehensive obesity curriculum presented to students in medical school can positively influence their attitudes toward obesity. METHODS: The study was designed around a comprehensive educational obesity curriculum at Touro University College of Osteopathic Medicine-CA, involving the classes of 2013 through 2018. A survey to assess student attitudes toward obesity was distributed to first-year students before the curriculum, directly after completion, and each year after until graduation (graduating classes of 2015 through 2018). Second- and third-year medical students in 2011 (graduating classes of 2014 and 2013), who did not complete the curriculum, were given an examination to establish baseline values and served as the control group. The obesity curriculum consisted of lectures delivered during the first and second year of medical school and case study simulations during the third year. Knowledge gained from the curriculum was assessed with a multiple-choice examination, and bias was assessed using the Fat Phobia Scale. RESULTS: A total of 718 first- through fourth-year students were included. Students who completed the first year of the obesity curriculum (n=528) showed significantly greater medical knowledge regarding obesity-related epidemiology, pathogenesis, biochemistry, pathophysiology, and metabolic factors; nutrition, diet, physical activity, self-control, and behavior modification; pharmacologic and nonpharmacologic interventions; and associated chronic disorders, based on their multiple-choice examination scores compared with the control group. The examination scores indicated significant increases in medical knowledge compared with the precurriculum cohort after the curriculum (OMS I students: 130 [72.4%]; 133 [92.6%]; 133 [91.1%]; 132 [89.0%]; vs control: 105 [47.2%]; 134 [52.6%], respectively [P<.01]). In all 4 years observed, there was a significant reduction in bias among first-year medical students after obesity curriculum (before: 3.65, 3.76, 3.57, 3.61, and after: 3.47, 3.38, 3.34, 3.37, respectively) (P<.05). The reduction in bias was also significantly sustained throughout the fourth year. CONCLUSION: A comprehensive obesity curriculum throughout medical school resulted in an improvement in students' attitudes toward and knowledge of obesity.

The "New Deadly Quartet" for cardiovascular disease in the 21st century: obesity, metabolic syndrome, inflammation and climate change: how does statin therapy fit into this equation?

Despite population-based improvements in cardiovascular risk factors, such as blood pressure, cholesterol and smoking, cardiovascular disease still remains the number-one cause of mortality in the United States. In 1989, Kaplan coined the term "Deadly Quartet" to represent a combination of risk factors that included upper body obesity, glucose intolerance, hypertriglyceridemia and hypertension [Kaplan in Arch Int Med 7:1514-1520, 1989]. In 2002, the third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP III) essentially added low HDL-C criteria and renamed this the "metabolic syndrome." [The National Cholesterol Education Program (NCEP) in JAMA 285:2486-2497, 2001] However, often forgotten was that a pro-inflammatory state and pro-thrombotic state were also considered components of the syndrome, albeit the panel did not find enough evidence at the time to recommend routine screening for these risk factors [The National Cholesterol Education Program (NCEP) in JAMA 285:2486-2497, 2001]. Now over a decade later, it may be time to reconsider this deadly quartet by reevaluating the roles of obesity and subclinical inflammation as they relate to the metabolic syndrome. To complete this new quartet, the addition of increased exposure to elevated levels of particulate matter in the atmosphere may help elucidate why this cardiovascular pandemic continues, despite our concerted efforts. In this article, we will summarize the evidence, focusing on how statin therapy may further impact this new version of the "deadly quartet".

Overweight and obesity: the pathogenesis of cardiometabolic risk.

Obesity, particularly abdominal adiposity, is increasingly recognized as a cause of elevated cardiometabolic risk--the risk of developing type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). The predominate mechanisms appear to involve the promotion of insulin resistance, driven largely by excess free fatty acids secreted by an expanded adipose tissue mass, and the development of an inflammatory milieu due to increased secretion of inflammatory cytokines and adipokines from adipose tissue. Key proinflammatory cytokines secreted by adipocytes include tumor necrosis factor-alpha, interleukin-6, leptin, resistin, and plasminogen activator inhibitor-1. All have been variously associated with hyperinsulemia, hyperglycemia, insulin resistance, diabetes, and endothelial dysfunction, as well as plaque development, progression, and rupture. Adiponectin, another important adipocyte, has protective cardiometabolic actions; however, adiponectin levels decline with increasing obesity. Understanding the role of obesity in the pathogenesis of cardiometabolic risk is crucial for the development of treatment strategies that will provide maximum benefit for patients with, or at risk for, type 2 DM and CVD.

Hemodynamic effects of osteopathic manipulative treatment immediately after coronary artery bypass graft surgery.

CONTEXT: Coronary artery bypass graft (CABG) surgery is a common procedure for patients with coronary artery disease. The physiologic effects of postoperative osteopathic manipulative treatment (OMT) following CABG have not been documented previously. OBJECTIVE: To determine the effects of OMT on cardiac hemodynamics post-CABG surgery. DESIGN: Pilot prospective clinical study (N=29). SETTING AND PATIENTS: Treatment subjects (n=10) undergoing CABG surgery were recruited for postoperative OMT. The primary assessment compared, pre-OMT versus post-OMT, measurements of thoracic impedance, mixed venous oxygen saturation (SvO2), and cardiac index. Records of control subjects (n=19) who underwent CABG surgery--but who did not receive OMT--were assessed for SvO2 and cardiac index at 1 hour and 2 hours postsurgery. INTERVENTION: Immediately following CABG surgery (< or = 2 h), OMT was provided to subjects to alleviate anatomic dysfunction of the rib cage caused by median sternotomy and to improve respiratory function. This adjunctive treatment occurred while subjects were completely anesthetized. RESULTS: A post-OMT increase in thoracic impedance (P < or = .02) in OMT subjects demonstrated that central blood volume was reduced after OMT, suggesting an improved peripheral circulation. Mixed venous oxygen saturation also increased (P < or = .005) after OMT. These increases were accompanied by an improvement in cardiac index (P < or = .01). Comparisons of postoperative measurements in OMT subjects versus those in control subjects revealed statistically significant differences for SvO2 (P < or = .005) and cardiac index (P < or = .02) between the two groups. CONCLUSION: The observed changes in cardiac function and perfusion indicated that OMT had a beneficial effect on the recovery of patients after CABG surgery. The authors conclude that OMT has immediate, beneficial hemodynamic effects after CABG surgery when administered while the patient is sedated and pharmacologically paralyzed.