Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations–State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist

Depression and anxiety in patients with suspected renal artery stenosis

Objective: To investigate the occurrence of depressive and anxiety disorders in patients remitted for endovascular treatment of renal artery stenosis (RAS), and whether symptoms of depression and anxiety can be reduced after the treatment of RAS with percutaneous transluminal renal angioplasty (PTRA).Methods Patients: Selected for renal angiography with pressure measurement in the renal arteries due to suspected RAS were invited to participate in the study. 37 patients agreed to answer a questionnaire. Eighteen patients also agreed to a clinical psychiatric examination including the International Neuropsychiatric Interview (M.I.N.I. 6.0) to be diagnosed according to the DSM-IV. Results: Twenty-one of the 37 patients completing the questionnaire were found to have a pressure gradient of ≥ 10 mmHg at angiography, indicating significant stenosis. Ten of the 18 examined patients met the criteria for current DSM-IV anxiety diagnosis and two patients had a current depression. Three of the 18 examined patients had previously made a suicide attempt. Conclusion: The results of this study suggest that patients with suspected RAS have a high psychiatric comorbidity, as 56% of the patients undergoing psychiatric examination met the DSM-IV criteria for a current anxiety disorder

Gender, autoantibodies, and obesity in newly diagnosed diabetic patients aged 40-75 years

OBJECTIVE - To evaluate the frequency of autoimmune markers (islet cell antibodies [ICA] and glutamic acid decarboxylase antibodies [GADA]) and clinical features in newly diagnosed people with diabetes aged 40-75 years. RESEARCH DESIGN AND METHODS - Two hundred fifty-nine consecutive patients (aged 40-75 years) with newly suspected diabetes diagnosed during a 2-year period were studied. The diagnosis of newly discovered diabetes was confirmed in 203 patients. Gender, BMI, HbA(1c), fasting C-peptide, ICA, and GADA were evaluated. The frequency of obesity was estimated using two different sets of criteria: 1) National Diabetes Data Group (NDDG) criteria, and 2) criteria based on a Swedish reference population. RESULTS - The annual incidence of diabetes was 106 per 100,000 people. The incidence of diabetes in those patients who were 40-54 years old was significantly higher in men than in women (odds ratio: 2.16; P = 0.001). ICA were detected in 16 of 203 patients (8%), whereas 17 of 203 patients (8%) were GADA+; 10 of 203 (5%) patients were positive for both ICA and GADA. Among the 203 diabetic patients, 19 (9.4%) were classified as having IDDM, giving an IDDM incidence of 10 per 100,000 people aged 40-75 years. The frequency of obesity in NIDDM was high but varied with its definition; the frequency of obesity was highest (P < 0.001) when NDDG criteria, and not Swedish reference values, were used (57 of 75 [76%] vs. 40 of 75 [53%] for women and 66 of 109 [61%] vs. 45 of 109 [41%] for men). CONCLUSIONS - A striking male preponderance was found among incident cases of diabetes in people aged 40-54 years. Autoimmune markers were detected in 10% of incident cases of diabetes in people aged 40-75 years. Using a conservative estimation, as many as 10 of 100,000 middle-aged and elderly subjects developed IDDM. The frequency of obesity in NIDDM was high but this was also the case in the reference population

Temporal trend of autonomic nerve function and HSP27, MIF and PAI-1 in type 1 diabetes

Aim: Diabetes mellitus type 1 (T1D) has numerous complications including autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their possible roles in effects of diabetes on the autonomic nervous system. Methods: Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were analyzed. Results: Autonomic nerve function deteriorated over time during the 20-year-period, but levels of HSP27, MIF, and PAI-1 were not associated with cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I-ratio. Conclusions: Neither the neuroprotective substance HSP27 nor the inflammatory substances, MIF and PAI-1 were associated with measures of cardiovascular autonomic nerve function, but a deterioration of such function was observed in relation to increasing HbA1c in T1D during a 20-year follow-up period. Improved glucose control might be associated with protection against autonomic neuropathy in T1D

Complement activation and plasma levels of C4b-binding protein in critical limb ischemia patients.

OBJECTIVE: Critical limb ischemia (CLI) is a peripheral arterial disease manifested by drastically diminished blood flow to the legs, pain at rest, nonhealing wounds, and gangrene caused by atherosclerosis. Significant tissue necrosis is associated with late stage CLI and the patients have a poor prognosis. Necrotic and apoptotic cells activate complement and bind complement inhibitor C4b-binding protein (C4BP). The major isoform of C4BP is composed of seven identical alpha-chains and one beta-chain, here termed C4BP(beta), whereas upon inflammation a normally less abundant isoform is upregulated that is exclusively composed of alpha-chains. Measuring the alpha-chains of C4BP includes both isoforms and is termed total C4BP (C4BP(tot)). The hypothesis of this study was that levels of complement activation and C4BP are predictive for the severity of the disease and that their measurement might be of clinical advantage. METHODS: This was a prospective, single-center study of 259 consecutive patients with CLI admitted to a secondary referral center for vascular diseases. Interventions included evaluation of soluble terminal complement complexes (C5b-9), C4BP(tot) and C4BP(beta), lipid levels, the inflammatory mediators tumor necrosis factor-alpha, interleukin-6, 8-iso-prostaglandin F(2alpha), high-sensitivity C-reactive protein, neopterin, plasma homocysteine, and plasma endothelin-1 in plasma as well as resistance to activated protein C and ankle blood pressure. All data were compared with an age-matched population based control group of 219 currently healthy individuals. RESULTS: The data are presented as mean +/- SEM/median. CLI patients showed systemic complement activation (1.17 +/- 0.06/1.13 AU/mL vs 0.69 +/- 0.07/0.59 AU/mL in healthy controls, P < .0001), which was even higher in patients with gangrene (1.33 +/- 0.11/1.28 AU/mL vs 1.1 +/- 0.08/1.0 AU/mL, P = .0264), who also showed increased C4BP levels (421 +/- 28.6/386 microg/mL vs 341 +/- 10.8/318 microg/mL for C4BP(tot), P = .0248; 374 +/- 25.4/332 microg/mL vs 305 +/- 9.5/285 microg/mL for C4BP(beta), P = .0581). C4BP plasma levels were significantly elevated in CLI patients in comparison to healthy controls (351 +/- 8.1/322 microg/mL vs 297 +/- 8.0/288 microg/mL for C4BP(tot), P = .0001; 314 +/- 7.0/287 microg/mL vs 265 +/- 7.0/263 microg/mL for C4BP(beta), P = .0004) and correlated to levels of interleukin-6 (P(tot/beta) = .0048/.0019), high-sensitivity C-reactive protein (P < .0001), leukocyte (P(tot/beta) = .0086/.0043) and platelet count (P = .0001), LDL/HDL ratio (P(tot) = .0151) and HDL (P(tot/beta) = .0047/.0177), but not to tumor necrosis factor-alpha. CONCLUSIONS: Increased complement activation and C4BP plasma levels are related to the degree of tissue necrosis and disease severity of critical limb ischemia. This knowledge in combination with the found correlations to other biomarkers is useful for understanding the pathophysiology of the disease

Thromboembolic Disease in Patients With Cancer and COVID-19:Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations–State-of-the-Art

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currently indicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARSCoV2 remains unclear. In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist

Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism

OBJECTIVES: The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. BACKGROUND: It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. METHODS: The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (n(e) = 4,572); venous thromboembolism (n(e) = 4,607); intracranial aneurysm (n(e) = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). RESULTS: LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 x 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). CONCLUSIONS: LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes