ContextThe association of triglycerides with incident cardiovascular disease remains controversial. Although triglyceride levels are typically obtained in the fasting state, postprandial hypertriglyceridemia may play an important role in atherosclerosis.ObjectiveTo determine the association of triglyceride levels (fasting vs nonfasting) and risk of future cardiovascular events.Design, Setting, and ParticipantsProspective study of 26 509 initially healthy US women (20 118 fasting and 6391 nonfasting) participating in the Women's Health Study, enrolled between November 1992 and July 1995 and undergoing follow-up for a median of 11.4 years. Triglyceride levels were measured in blood samples obtained at time of enrollment.Main Outcome MeasureHazard ratios for incident cardiovascular events (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, or cardiovascular death).ResultsAt baseline, triglyceride levels in fasting as well as nonfasting women correlated with traditional cardiac risk factors and markers of insulin resistance. During a median follow-up of 11.4 years, 1001 participants experienced an incident cardiovascular event (including 276 nonfatal myocardial infarctions, 265 ischemic strokes, 628 coronary revascularizations, and 163 cardiovascular deaths), for an overall rate of 3.46 cardiovascular events per 1000 person-years of follow-up. After adjusting for age, blood pressure, smoking, and use of hormone therapy, both fasting and nonfasting triglyceride levels predicted cardiovascular events. Among fasting participants, further adjustment for levels of total and high-density lipoprotein cholesterol and measures of insulin resistance weakened this association (fully adjusted hazard ratio [95% confidence interval] for increasing tertiles of triglyceride levels: 1 [reference], 1.21 [0.96-1.52], and 1.09 [0.85-1.41] [P = .90 for trend]). In contrast, nonfasting triglyceride levels maintained a strong independent relationship with cardiovascular events in fully adjusted models (hazard ratio [95% confidence interval] for increasing tertiles of levels: 1 [reference], 1.44 [0.90-2.29], and 1.98 [1.21-3.25] [P = .006 for trend]). In secondary analyses stratified by time since participants' last meal, triglyceride levels measured 2 to 4 hours postprandially had the strongest association with cardiovascular events (fully adjusted hazard ratio [95% confidence interval] for highest vs lowest tertiles of levels, 4.48 [1.98-10.15] [P<.001 for trend]), and this association progressively decreased with longer periods of fasting.ConclusionsIn this cohort of initially healthy women, nonfasting triglyceride levels were associated with incident cardiovascular events, independent of traditional cardiac risk factors, levels of other lipids, and markers of insulin resistance; by contrast, fasting triglyceride levels showed little independent relationship.

https://jamanetwork.com/journals/jama/articlepdf/208018/joc70074_309_316.pdf

Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women.

The key initiating process in atherogenesis is the subendothelial retention of apolipoprotein B-containing lipoproteins. Local biological responses to these retained lipoproteins, including a chronic and maladaptive macrophage- and T-cell-dominated inflammatory response, promote subsequent lesion development. The most effective therapy against atherothrombotic cardiovascular disease to date—low density lipoprotein-lowering drugs—is based on the principle that decreasing circulating apolipoprotein B lipoproteins decreases the probability that they will enter and be retained in the subendothelium. Ongoing improvements in this area include more aggressive lowering of low-density lipoprotein and other atherogenic lipoproteins in the plasma and initiation of low-density lipoprotein-lowering therapy at an earlier age in at-risk individuals. Potential future therapeutic approaches include attempts to block the interaction of apolipoprotein B lipoproteins with the specific subendothelial matrix molecules that mediate retention and to interfere with accessory molecules within the arterial wall that promote retention such as lipoprotein lipase, secretory sphingomyelinase, and secretory phospholipase A2. Although not the primary focus of this review, therapeutic strategies that target the proatherogenic responses to retained lipoproteins and that promote the removal of atherogenic components of retained lipoproteins also hold promise. The finding that certain human populations of individuals who maintain lifelong low plasma levels of apolipoprotein B lipoproteins have an 90% decreased risk of coronary artery disease gives hope that our further understanding of the pathogenesis of this leading killer could lead to its eradication. (Circulation. 2007;116:1832-1844.)

Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis: Update and Therapeutic Implications

Clearly, insulin resistance is not simply a problem of deficient glucose uptake in response to insulin, but a multifaceted syndrome that increases significantly the risk for cardiovascular disease. The links between insulin resistance and the associated dyslipidemia, hypertension, hypercoagulability, and atherosclerosis are numerous and complex. This complexity derives both from the almost certain multiple causes of the insulin resistance syndrome and from the interaction of genes predisposing to insulin resistance with other genes that have their own, independent impact on lipid metabolism, blood pressure regulation, coagulation, and artery wall biology. Nonetheless, I suggest that dysregulation of fatty acid metabolism plays a central role in the development of this phenotype. Thus, the association between insulin resistance and dyslipidemia is clearly initiated by increased FFA release from, or defective uptake of FFAs into, adipocytes. Recent studies linking fatty acids to endothelial dysfunction, together with the clear role of VLDL in the stimulation of PAI-1, further support the view that dysregulation of fatty acid metabolism sits close to the center of the pathophysiology of the insulin resistance syndrome, at least as it relates to risk for cardiovascular disease.

/pdf/insulin-resistance-and-cardiovascular-disease-jt4wug42jg.pdf

Insulin resistance and cardiovascular disease

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.

/pdf/triglyceride-rich-lipoproteins-and-high-density-lipoprotein-52yxf6d3zf.pdf

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis.

We isolated and characterized immunoreactive apolipoprotein B (apoB)-containing lipoproteins from human atherosclerotic plaque and plasma to determine whether very-low-density lipoprotein (VLDL) can enter and become incorporated into the atherosclerotic lesion and how plaque apoB-containing lipoproteins differ from apoB-containing lipoproteins isolated from plasma. Atherosclerotic plaques were obtained during aortic surgery and processed immediately. Lipoproteins were extracted from minced plaque in a buffered saline solution (extract A). In selected cases a second extraction was done after plaque was incubated with collagenase (extract B). Lipoproteins were then isolated from the extracts by anti-apoB immunosorption and separated into VLDL + intermediate-density lipoprotein (IDL) (d < 1.019 g/mL) and low-density lipoprotein (LDL) (1.019 < d < 1.070 g/mL) fractions by ultracentrifugation. The VLDL + IDL fractions from plaque contained more than one third of the total apoB-associated lipoprotein cholesterol in both extracts A and B. The lipid composition of VLDL + IDL in both extracts was related to that of plasma VLDL + IDL. By electron microscopy mean particle diameters of VLDL + IDL from extracts A and B were 9% and 23%, respectively, greater than VLDL + IDL diameters from plasma. Mean diameters of LDL from extracts A and B were 11% and 31% greater than LDL diameters from plasma. The apoE-apoB ratio of extract A VLDL + IDL was nearly twice that of plasma VLDL + IDL and severalfold higher than that of extract A LDL. Immunoblots of both VLDL + IDL and LDL from extract A demonstrated minimal fragmentation of apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

Triglyceride-rich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque.

BACKGROUND To examine the relation of plasma lipoproteins to the proliferative response after arterial injury in humans, we examined the plasma lipid, lipoprotein, and apoprotein levels of 20 patients with early recurrent stenosis caused by intimal hyperplasia after carotid endarterectomy. These were compared with 20 controls who had no evidence of recurrent stenosis by duplex ultrasound scanning. METHODS AND RESULTS By univariate analysis, the reoperated patients had higher levels of plasma cholesterol (251 versus 225 mg/dl, p less than 0.05), total triglycerides (173 versus 105 mg/dl, p less than 0.03), and low density lipoprotein (LDL) apoprotein B (99.8 versus 77.2 mg/dl, p less than 0.003). The ratio of cholesterol to apoprotein B in LDL was lower in patients with restenosis (p less than 0.04), suggesting LDL of smaller diameter. High density lipoprotein (HDL) cholesterol level was reduced (45 versus 55 mg/dl, p less than 0.01) in patients with restenosis. With statistical adjustment for the correlations between these variables by multivariate analysis, both LDL apoprotein B and HDL cholesterol were independent predictors of the risk of restenosis. Ten patients with restenosis but only two controls had one or two apolipoprotein E4 alleles. CONCLUSIONS Elevated lipid levels usually associated with an increased risk of atherosclerosis may predispose patients to an increased incidence of intimal hyperplasia after endarterectomy.

Relation of plasma lipid and apoprotein levels to progressive intimal hyperplasia after arterial endarterectomy.

To determine the rate of symptomatic venous thromboembolism (VTE) among patients undergoing arthroscopic knee procedures, risk factors associated with postoperative VTE, and current perioperative thromboprophylaxis prescription patterns associated with this population in the United States.Medical records for patients ≥18 years of age were queried from the Mariner database using Current Procedural Terminology codes for knee arthroscopy performed in the United States from 2010 to 2020 in this cross-sectional study. Patients who received thromboprophylaxis and those diagnosed with VTE, including deep-vein thrombosis or pulmonary embolism, within 90 days of surgery were identified using International Classification of Diseases and National Drug Codes. Two multivariable logistic regression models were used to identify VTE risk factors and likelihood of perioperative thromboprophylaxis. Covariates included procedure type, age, oral contraceptive pill (OCP) use, and medical comorbidities.A total of 718,289 patients met inclusion criteria and 7,618 patients (1.06%) experienced VTE, including deep-vein thrombosis (n = 6,394, 0.9%) and/or pulmonary embolism (n = 2,211, 0.3%). A total of 10,769 patients (1.5%) filled perioperative thromboprophylaxis, including aspirin (n = 5,353, 0.7%), low-molecular-weight heparin (n = 4,563, 0.6%), and oral factor Xa inhibitors (n = 947, 0.1%). Perioperative thromboprophylaxis was associated with decreased odds of experiencing VTE (adjusted odds ratio [aOR] 0.65, 95% confidence interval [CI] 0.51-0.80). Procedure types categorized as moderate-to-greater risk were associated with increased odds of VTE (aOR 1.42, 95% CI 1.34-1.50). OCP use (aOR 1.63, 95% CI 1.38-1.91), obesity (aOR 1.17, 95% CI 1.11-1.24), renal disease (aOR 1.33, 95% CI 1.18-1.50) and congestive heart failure (aOR 1.30, 95% CI 1.13-1.50) were associated with increased odds of VTE.While the overall rate of symptomatic VTE following knee arthroscopy remains low, procedure types that are more complex and generally require restrictive rehabilitation protocols, OCP use, obesity, renal disease, and congestive heart failure are associated with increased odds of postoperative VTE. Conversely, the use of perioperative thromboprophylaxis is associated with significantly lower VTE risk.III, retrospective comparative prognostic trial. 

Perioperative Thromboprophylaxis Is Associated With Lower Risk of Venous Thromboembolism After Knee Arthroscopy.

Objectives: Incidence of venous thromboembolism (VTE) after knee arthroscopy is reportedly low, but rates vary significantly across literature. Current guidelines recommend against routine perioperative thromboprophylaxis, but prescribing practices and VTE risk factors are poorly understood. Methods: Medical records for patients ≥18 years of age were queried from the Pearl Diver database using CPT codes for arthroscopic knee procedures. Patients with a previous diagnosis of VTE or hyper-coagulable disorder were excluded from analyses. Procedures were grouped by rehabilitation protocols, with restrictive procedures requiring a period of non-weightbearing or postoperative immobilization. Patients who received perioperative thromboprophylaxis were identified. Patients diagnosed with VTE, including pulmonary embolism and/or deep vein thrombosis, within 90 days of surgery were identified using International Classification of Diseases (ICD) codes. Multivariable logistic regression models were utilized to identify VTE risk factors and likelihood of thromboprophylaxis prescription. Covariates included age, restrictive rehabilitation protocols, oral contraceptive pill (OCP) use, and medical comorbidities. Results: A total of 718,289 patients underwent knee arthroscopy from 2011 to 2020. 10,769 patients (1.5%) received perioperative thromboprophylaxis, including aspirin (n=5,353, 0.7%), low molecular weight heparin (n=4,563, 0.6%) and factor Xa inhibitors (n=947, 0.1%). A total of 7,618 patients (1.1%) experienced VTE. Perioperative prophylaxis was associated with decreased odds of experiencing VTE (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] = 0.51 to 0.79) (Table 1). Restrictive procedure type was associated with increased odds of experiencing VTE (aOR =1.42, 95% CI = 1.34 to 1.50) and receiving prophylaxis (aOR=1.95, 95% CI = 1.87 to 2.05). OCP use (aOR = 1.63, 95% CI = 1.37 to 1.91), renal disease (aOR = 1.33, 95% CI = 1.18 to 1.50) and congestive heart failure (aOR = 1.30, 95% CI = 1.13 to 1.49) were associated with increased odds of VTE. Tobacco use was associated with increased odds of VTE (aOR = 1.12, 95% CI 1.03 to 1.22), but decreased odds of receiving perioperative prophylaxis (aOR = 0.84, 95% CI 0.78 to 0.91). Malignancy was associated with increased odds of receiving prophylaxis (aOR = 1.18, 95% CI 1.09 to 1.29) but not with increased odds of VTE. Conclusions: Procedures with restrictive rehabilitation protocols, OCP use, renal disease, and congestive heart failure are associated with increased odds of VTE following knee arthroscopy. Conversely, the use of perioperative thromboprophylaxis is associated with significantly lower odds of VTE. Risk factors for postoperative VTE are not always correlated with increased likelihood of receiving perioperative thromboprophylaxis. Patients with a tobacco use history may be an at-risk population that can be better selected for thromboprophylaxis when clinically appropriate. Table 1. Multivariable Logistic Model of VTE and Perioperative Thromboprophylaxis Odds

Poster 222: Venous Thromboembolism Risk factors and Prophylaxis Patterns in Knee Arthroscopy: A Large Database Study

Intra-articular ganglion cysts in the knee large enough to cause neurovascular claudication are rare entities only identified in singular case reports. The severity of claudication can cause debilitating symptoms and pain to previously highly functional and asymptomatic patients. Total knee arthroplasty has been described to treat these cysts in elderly patients with osteoarthritis, although this treatment pathway may not appeal to patients without antecedent pain and high activity levels. This surgical report will detail a reproducible method of arthroscopic decompression of posterior, intra-articular cysts to relieve vascular claudication by highlighting technical pearls in navigating posterior knee arthroscopy. 

http://www.arthroscopytechniques.org/article/S2212628722001529/pdf

N Colyvas

Papers

Triglyceride-rich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque.

Relation of plasma lipid and apoprotein levels to progressive intimal hyperplasia after arterial endarterectomy.

Perioperative Thromboprophylaxis Is Associated With Lower Risk of Venous Thromboembolism After Knee Arthroscopy.

Poster 222: Venous Thromboembolism Risk factors and Prophylaxis Patterns in Knee Arthroscopy: A Large Database Study

Arthroscopic Decompression of a Posterior Knee Cyst Causing Vascular Compression