Influence of lipoprotein (a) on inflammatory biomarkers in metabolic syndrome.

OBJECTIVE: To examine the relation between plasma lipoprotein (a) (Lp[a]) levels and oxidative stress biomarkers, serum cytokines, and atherosclerotic burden among individuals recently diagnosed as having metabolic syndrome (MS). METHODS: Eighty-four white patients with MS were classified according to two Lp(a) levels (normal Lp[a]: < 30 mg/dL or high Lp[a]: > 30 mg/dL) and were compared with 42 healthy controls. Oxidative stress biomarkers (oxidized low-density lipoprotein, antibodies to oxidized low-density lipoprotein, and nitric oxide metabolites) and proinflammatory cytokines (interleukin [IL]-2, IL-4, IL-5, IL-6, IL-10, IL-12P70, IL-13, and interferon-γ) were measured in plasma. Atherosclerotic significance was determined using carotid ultrasound and endothelial function by standardized protocols. RESULTS: Patients with MS had higher levels of serum cytokines, oxidative stress markers, and C-reactive protein, and greater atherosclerosis burden as compared with controls. Among the group members, 58 patients had normal Lp(a) levels and 26 had high Lp(a) levels. Cytokines and C-reactive protein levels were significantly higher in patients with high Lp(a) compared with those with normal Lp(a) (P < 0.01 for IL-2 and P < 0.001 for the others). Nitric oxide metabolites were significantly lower in patients with high Lp(a) as compared with those with normal Lp(a) (P < 0.05). No differences were found in oxidized low-density lipoprotein and atherosclerotic burden between the two groups of patients with MS with respect to Lp(a) levels. CONCLUSIONS: Elevated Lp(a) plasma levels are associated with higher proinflammatory markers in patients newly diagnosed as having MS.

A RIETE registry analysis of patients with upper extremity deep vein thrombosis and thoracic outlet syndrome.

BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) related to thoracic outlet syndrome (TOS) is rare, and the literature is limited to institutional case series. METHODS: We used data from the RIETE Registry to compare outcomes (recurrences, major bleeding and signs and symptoms of post-thrombotic [PTS] syndrome) in patients with UEDVT and TOS undergoing first rib resection vs. those not undergoing surgery. RESULTS: From March 2001 to March 2021, there were 4214 patients with UEDVT, of whom 209 (4.96%) had TOS. Of these, 55 (26%) underwent first rib resection. Patients with TOS were younger and less likely to have comorbidities than those without TOS. There were no differences between patients with TOS undergoing surgery and those who did not. During anticoagulation, patients with TOS had a non-statistically significant lower rate of VTE recurrences than those without TOS (hazard ratio [HR]: 0.46; 95%CI: 0.14-1.12) and a lower bleeding rate (HR: 0.16; 95%CI: 0.01-0.83). No patient with TOS developed pulmonary embolism or died. Patients with TOS undergoing surgery had fewer PTS symptoms (odds ratio [OR]: 0.21; 95%CI: 0.06-0.68) or signs (OR: 0.11; 95%CI: 0.02-0.42) after one year than patients who did not have surgery. At two years, the differences in symptoms (OR: 0.25; 95%CI: 0.06-0.94) and signs (OR: 0.04; 95%CI: 0.002-0.33) persisted. CONCLUSIONS: Patients with UEDVT and TOS were younger and had less comorbidities than those without. Surgical resection of the first rib was associated with a lower proportion of patients developing PTS one and two years later.

Alcohol consumption and outcome in stable outpatients with peripheral artery disease.

BACKGROUND: The influence of alcohol consumption on outcome in patients with peripheral artery disease (PAD) has not been thoroughly studied. METHODS: Factores de Riesgo y ENfermedad Arterial (FRENA) is an ongoing, multicenter, observational registry of consecutive stable outpatients with arterial disease. We compared the mortality rate and the incidence of subsequent ischemic events in patients with PAD, according to their alcohol habits. RESULTS: As of August 2010, 1073 patients with PAD were recruited, of whom 863 (80%) had intermittent claudication (Fontaine stage II), 102 (9.5%) had rest pain (Fontaine stage III), and 108 (10%) had ischemic skin lesions (Fontaine stage IV). In all, 422 patients (39%) consumed alcohol during the study period. Over a mean follow-up of 13 months, 150 patients (14%) developed subsequent ischemic events (myocardial infarction 28, stroke 30, disabling claudication/critical limb ischemia 100), and 70 patients (6.5%) died. The incidence of subsequent events was the same in both subgroups: 11.8 events per 100 patient-years (rate ratio: 1.00; 95% confidence interval [CI], 0.72-1.41), but the mortality rate was significantly lower in alcohol consumers than in non-consumers: 2.78 vs 6.58 deaths per 100 patient-years (rate ratio: 0.42; 95% CI, 0.23-0.74; P = .002). This better outcome was consistently found in patients with Fontaine stages II and III or IV, and persisted after multivariate adjustment (relative risk: 0.49; 95% CI, 0.28-0.88). CONCLUSIONS: In patients with PAD, moderate alcohol consumption was associated with lower cardiovascular mortality and overall mortality than abstention. These patients should be informed that low to moderate alcohol consumption may not be harmful to their health.

Effects of age on the risk of dying from pulmonary embolism or bleeding during treatment of deep vein thrombosis.

BACKGROUND: The risk of patients dying of pulmonary embolism (PE) or bleeding during the treatment of deep vein thrombosis (DVT), and whether these risks are influenced by patient age, has not been thoroughly studied. METHODS: We used data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) to assess the risk of fatal PE and fatal bleeding in 16,199 patients with lower limb DVT (without symptomatic PE at the time of inclusion) during the 3 months after diagnosis, with patients categorized according to age. RESULTS: During the 3 months of anticoagulant treatment, there were 31 fatal PEs (0.19%) and 83 fatal hemorrhages (0.51%). During the first 7 days of therapy, the frequency of fatal PEs was similar to that of fatal bleeding (12 vs 14 deaths, respectively; odds ratio [OR], 0.86; 95% confidence interval [CI], 0.39-1.87). However, from days 8 to 90, the frequency of fatal bleeding was greater than that of fatal PE (69 vs 19 deaths; OR, 3.64; 95% CI, 2.22-6.20). The higher frequency of fatal bleeding compared with fatal PE from days 8 to 90 appeared to be confined to patients who were aged ≥ 60 years. Multivariate analysis showed that patient age was independently associated with an increased risk of death from bleeding during the first 3 months: every 10 years the OR increased by 1.37 (95% CI, 1.12-1.67). CONCLUSIONS: During the first week of treatment, the risk of fatal bleeding and fatal PE were similar. Then, particularly in patients who were aged ≥ 60 years, the risk of dying from bleeding exceeded the risk of dying from PE.

Concomitant use of proton pump inhibitors and clopidogrel in patients with coronary, cerebrovascular, or peripheral artery disease in the factores de Riesgo y ENfermedad Arterial (FRENA) registry.

BACKGROUND: Among patients receiving clopidogrel for coronary artery disease, concomitant therapy with proton pump inhibitors (PPIs) has been associated with an increased risk for recurrent coronary events. PATIENTS AND METHODS: Factores de Riesgo y ENfermedad Arterial (FRENA) is an ongoing, multicenter, observational registry of consecutive outpatients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. We retrospectively examined the influence of concomitant use of PPIs on outcome in patients receiving clopidogrel. RESULTS: As of March 2009, 1222 patients were using clopidogrel: 595 had coronary artery disease, 329 cerebrovascular disease, and 298 had peripheral artery disease. Of these, 519 (42%) were concomitantly using PPIs. Over a mean follow-up of 15 months, 131 patients (11%) had 139 subsequent ischemic events: myocardial infarction 44, ischemic stroke 40, and critical limb ischemia 55. Seventeen of them (13%) died within 15 days of the subsequent event. PPI users had a higher incidence of myocardial infarction (rate ratio, 2.5; 95% confidence interval [CI], 1.3-4.8), ischemic stroke (rate ratio, 1.9; 95% CI, 1.03-3.7), and a nonsignificantly higher rate of critical limb ischemia (rate ratio, 1.6; 95% CI, 0.95-2.8) than nonusers. On multivariate analysis, concomitant use of clopidogrel and PPIs was independently associated with an increased risk for subsequent ischemic events both in the whole series of patients (hazard ratio, 1.8; 95% CI, 1.1-2.7) and in those with cerebrovascular disease or peripheral artery disease (hazard ratio, 1.5; 95% CI, 1.01-2.4). CONCLUSIONS: In patients with established arterial disease, concomitant use of PPIs and clopidogrel was associated with a nearly doubling of the incidence of subsequent myocardial infarction or ischemic stroke. This higher incidence persisted after multivariate adjustment.

Evaluation of the SAMe-TT2R2 score to predict the quality of anticoagulation control in patients with venous thromboembolism treated with vitamin K antagonists: Findings from the RIETE registry.

BACKGROUND: The time in therapeutic range (TTR) of patients with venous thromboembolism (VTE) treated with vitamin K antagonists (VKA) is usually below recommended, leading to higher frequency of vascular events, bleeding and mortality. The SAMe-TT2R2 prediction score discriminates those patients with high or low probability of obtaining poor INR control and its use is recommended in patients with atrial fibrillation. Its usefulness has been evaluated in patients with VTE, with conflicting results. METHOD: We included consecutive patients enrolled in Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective multicenter VTE registry, treated with VKA for >90 days and a minimum of 3 INR determinations. We analyzed the relationship between the SAMe-TT2R2 score and TTR, determined by the Rosendaal method and by the percentage of INR determinations (after excluding the first month). A ROC curve was calculated considering a cut-off point of TTR ≥65% for good anticoagulation control. RESULTS: 3893 patients were included and classified in high (1411 patients) or low (2482 patients) probability of obtaining poor INR control according to the total score obtained (0-1 points versus 2 points, respectively). TTR, calculated by direct method and Rosendaal method, was 51.2 (±23.4) and 55.4 (±25.9) in the high probability group; and 54.4 (±23.0) and 58.2 (±25.6) in the low probability group, respectively (p < 0.001 for both comparisons). The outcomes were similar between groups. The predictive capacity of the SAMe-TT2R2 score showed an area under the ROC curve of 0.54 (CI 95% 0.52-0.56) and 0.53 (CI 95% 0.51-0.55). CONCLUSIONS: In patients with VTE treated with VKA, the SAMe-TT2R2 score discriminated those patients with high probability of obtaining poor INR control, but with a low predictive capacity. Further studies are required to assess the usefulness of the score in clinical decision-making.

Body mass index and outcome in patients with coronary, cerebrovascular, or peripheral artery disease: findings from the FRENA registry.

BACKGROUND: The relationship between body mass index (BMI) and mortality in patients with established arterial disease remains controversial. METHODS: FRENA is an ongoing, observational registry of consecutive outpatients with coronary artery disease (CAD), cerebrovascular disease, or peripheral artery disease (PAD). We examined the prognostic importance of accepted BMI categories on outcome among patients in the FRENA registry. RESULTS: In April 2008, 2274 patients (mean age, 66 years) had been enrolled, of whom 14 (0.6%) were underweight; 533 (23%) normal; 1051 (46%) overweight; and 676 (30%) were obese. Over a mean follow-up of 14 months, the incidence of major cardiovascular events (myocardial infarction, ischemic stroke, or critical limb ischemia) per 100 patient-years was: 7.1 [95% confidence interval (CI): 0.4-35]; 11 (95% CI: 8.4-14); 6.9 (95% CI: 5.6-8.5); and 8.5 (95% CI: 6.6-11), respectively. Their cardiovascular mortality was: 7.1 (95% CI: 0.4-35); 4.1 (95% CI: 5.9-11); 1.3 (95% CI: 0.9-2.3); and 1.5 (95% CI: 1.4-3.5), respectively. On multivariate analysis, the hazard ratio for cardiovascular mortality was: 2.2 (95% CI: 0.3-17); 1.0 (reference); 0.37 (95% CI: 0.20-0.69); and 0.37 (95% CI: 0.18-0.73), respectively. Survival benefit was only found in patients with CAD or PAD. Weight loss had little influence on outcome. CONCLUSION: Patients with CAD or PAD (not those with cerebrovascular disease) have an inverse correlation between BMI and cardiovascular mortality, even after adjusting for confounding variables.

Recurrence of venous thromboembolism in patients with recent gestational deep vein thrombosis or pulmonary embolism: Findings from the RIETE Registry.

INTRODUCTION: The aim of this study was to investigate the recurrence rate of venous thromboembolism (VTE) and the prevalence of major bleeding or death in patients with previous VTE in pregnancy and puerperium. Risk factors for VTE recurrence were also assessed. MATERIALS AND METHODS: We evaluated a cohort of patients enrolled in the international, multicenter, prospective Registro Informatizado de la Enfermedad Trombo-Embólica (RIETE) registry with objectively confirmed VTE. RESULTS: In the registry, 607 women were presenting with VTE that occurred during pregnancy or puerperium. The 2-year VTE recurrence rate was 3.3% (CI: 95 1.5-5.0%) and the recurrent VTE incidence rate was 2.28events/100 patients-year. Among the 16 cases of VTE recurrence 11 cases appeared during drug treatment while only five cases were diagnosed after therapy discontinuation. No significant difference was found in treatment duration among these two subgroups of VTE recurrence cases and women without recurrence. Furthermore, the use of thrombolytics and inferior vena cava filter in initial treatment was associated to an increased risk of VTE recurrence. CONCLUSIONS: The current study provides new insights on VTE recurrence rate in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) that occurred in pregnancy or postpartum period. These findings can contribute to risk assessment of thrombotic burden, thereby allowing for better decision making regarding antithrombotic management in this clinical setting.

Anemia and Outcome in Outpatients With Peripheral Artery Disease.

The influence of anemia on outcome in stable outpatients with peripheral artery disease (PAD) has not been consistently investigated. We used data from the Factores de Riesgo y ENfermedad Arterial (FRENA) Registry to compare ischemic events and mortality rates in stable outpatients with symptomatic PAD and anemia. Of 1663 patients with PAD, 208 (12.5%) had anemia. Over 18 months, patients with anemia had a higher rate of myocardial infarction (MI; rate ratio [RR]: 2.10; 95% confidence interval [CI]: 1.04-3.99), limb amputation (RR: 2.98; 95%CI: 1.70-5.05), and higher mortality (RR: 3.58; 95%CI: 2.39-5.28) than those without anemia. The rates of ischemic stroke (RR: 0.75; 95%CI: 0.23-1.93) and major bleeding (RR: 0.93; 95%CI: 0.15-3.51) were similar. On multivariable analysis, anemia was associated with an increased risk to die (hazard ratio [HR]: 2.32; 95%CI: 1.53-3.50) but not to develop MI (HR: 1.49; 95%CI: 0.73-3.05) or to have limb amputation (HR: 1.49; 95%CI: 0.86-2.59). In stable outpatients with PAD, anemia was associated with increased mortality but not with an increased rate of subsequent ischemic events or major bleeding.

Thrombophilia testing in patients with venous thromboembolism. Findings from the RIETE registry.

BACKGROUND: There is scarce information on the management habits with regard to thrombophilia testing in patients with venous thromboembolism (VTE). PATIENTS AND METHODS: RIETE is an ongoing registry of consecutive patients with symptomatic VTE. Aimed to estimate the extent to which thrombophilia test ordering patterns are consistent with the recommendations by a 2005 international consensus statement, we retrospectively compared the clinical characteristics of all patients tested for thrombophilia and those who were not tested. RESULTS: Of 21367 patients enrolled, 4494 (21%) were tested for thrombophilia: 1456 (32%) tested positive, 3038 (68%) negative. The most common abnormalities were: Factor V Leiden (N=376), antiphospholipid syndrome (N=289), and prothrombin G20210A (N=263). Overall, 12740 (60%) patients met one or more criteria of the consensus statement: 7894 (37%) had a first episode of idiopathic VTE; 4013 (19%) were aged <50 years; 133 (0.6%) were pregnant women; 758 (3.5%) were using estrogens; 3375 (16%) had recurrent VTE. Of them, 3618 (28%) underwent thrombophilia tests, 34% of whom tested positive. The percentage of patients testing positive was significantly higher in those aged <50 years, with no differences between idiopathic or secondary, first episode or recurrent VTE. Finally, 876 (10%) of the 8627 (40%) patients meeting no criteria were tested. Of these, 208 (24%) tested positive. CONCLUSIONS: Twenty-eight percent of patients meeting one or more criteria for thrombophilia testing, and 10% of those with no criteria were actually tested. Thus, a substantial proportion of thrombophilia ordering is not consistent with the recommendations made by the consensus statement.

Pulmonary embolism in patients with chronic obstructive pulmonary disease or congestive heart failure.

BACKGROUND: The diagnosis of pulmonary embolism (PE) is often unreliable in patients with chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF). SUBJECTS AND METHODS: Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) is an ongoing registry of consecutive patients with acute venous thromboembolism. In this study, the clinical characteristics, laboratory findings, and clinical outcomes of all enrolled patients with acute PE, with or without underlying cardiopulmonary diseases, were compared and contrasted. In addition, the performance of 2 clinical models for the diagnosis of PE was retrospectively evaluated. RESULTS: As of January 2005, 4444 patients with symptomatic PE have been enrolled in RIETE. Of those, 632 patients (14%) had COPD and 422 (9.5%) had CHF. Significant differences were found in clinical presentation and 3-month outcomes among the 3 groups. With the Geneva model, there was a lower percentage of PE patients with COPD (relative risk [RR] 0.82; 95% confidence interval [CI], 0.66-1.02) or CHF (RR 0.73; 95% CI, 0.56-0.95) who fell into the low pretest probability category, compared with patients with neither. Besides, the percentage of patients with high probability of PE was similar among the 3 patient groups. The frequency of COPD (61%) and CHF (72%) patients with a high pretest probability for PE increased when using the Pisa score, but the percentage of COPD patients into the high probability group was lower (RR 0.60; 95% CI, 0.51-0.71). CONCLUSIONS: Significant differences exist in PE patients with and without underlying cardiopulmonary diseases. The performance of the 2 clinical prediction models varied according to the presence or absence of underlying COPD or CHF.