Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the ...other. Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism, and evidence from randomized trials is lacking.
We randomly assigned 17,802 apparently healthy men and women with both low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to receive rosuvastatin, 20 mg per day, or placebo. We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis.
During a median follow-up period of 1.9 years (maximum, 5.0), symptomatic venous thromboembolism occurred in 94 participants: 34 in the rosuvastatin group and 60 in the placebo group. The rates of venous thromboembolism were 0.18 and 0.32 event per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio with rosuvastatin, 0.57; 95% confidence interval CI, 0.37 to 0.86; P=0.007); the corresponding rates for unprovoked venous thromboembolism (i.e., occurring in the absence of a known malignant condition, trauma, hospitalization, or surgery) were 0.10 and 0.17 (hazard ratio, 0.61; 95% CI, 0.35 to 1.09; P=0.09) and for provoked venous thromboembolism (i.e., occurring in patients with cancer or during or shortly after trauma, hospitalization, or surgery), 0.08 and 0.16 (hazard ratio, 0.52; 95% CI, 0.28 to 0.96; P=0.03). The rates of pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group (hazard ratio, 0.77; 95% CI, 0.41 to 1.45; P=0.42), whereas the rates of deep-vein thrombosis only were 0.09 and 0.20, respectively (hazard ratio, 0.45; 95% CI, 0.25 to 0.79; P=0.004). Consistent effects were observed in all the subgroups examined. No significant differences were seen between treatment groups in the rates of bleeding episodes.
In this trial of apparently healthy persons, rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism. (ClinicalTrials.gov number, NCT00239681.)
Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as ...cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.
We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes.
The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval CI, 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes.
In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.)
Summary Background Statins lower high-sensitivity C-reactive protein (hsCRP) and cholesterol concentrations, and hypothesis generating analyses suggest that clinical outcomes improve in patients ...given statins who achieve hsCRP concentrations less than 2 mg/L in addition to LDL cholesterol less than 1·8 mmol/L (<70 mg/dL). However, the benefit of lowering both LDL cholesterol and hsCRP after the start of statin therapy is controversial. We prospectively tested this hypothesis. Methods In an analysis of 15 548 initially healthy men and women participating in the JUPITER trial (87% of full cohort), we prospectively assessed the effects of rosuvastatin 20 mg versus placebo on rates of non-fatal myocardial infarction, non-fatal stroke, admission for unstable angina, arterial revascularisation, or cardiovascular death (prespecified endpoints) during a maximum follow-up of 5 years (median 1·9 years), according to on-treatment concentrations of LDL cholesterol (≥1·8 mmol/L or <1·8 mmol/L) and hsCRP (≥2 mg/L or <2 mg/L). We included all events occurring after randomisation. This trial is registered with ClinicalTrials.gov , number NCT00239681. Findings Compared with placebo, participants allocated to rosuvastatin who achieved LDL cholesterol less than 1·8 mmol/L had a 55% reduction in vascular events (event rate 1·11 vs 0·51 per 100 person-years; hazard ratio HR 0·45, 95% CI 0·34–0·60, p<0·0001), and those achieving hsCRP less than 2 mg/L a 62% reduction (event rate 0·42 per 100 person-years; HR 0·38, 95% CI 0·26–0·56, p<0·0001). Although LDL cholesterol and hsCRP reductions were only weakly correlated in individual patients ( r values <0·15), we recorded a 65% reduction in vascular events in participants allocated to rosuvastatin who achieved both LDL cholesterol less than 1·8 mmol/L and hsCRP less than 2 mg/L (event rate 0·38 per 100 person-years; adjusted HR 0·35, 95% CI 0·23–0·54), versus a 33% reduction in those who achieved one or neither target (event rate 0·74 per 100 person-years; HR 0·67, 95% CI 0·52–0·87) (p across treatment groups <0·0001). In participants who achieved LDL cholesterol less than 1·8 mmol/L and hsCRP less than 1 mg/L, we noted a 79% reduction (event rate 0·24 per 100 person-years; HR 0·21, 95% CI 0·09–0·52). Achieved hsCRP concentrations were predictive of event rates irrespective of the lipid endpoint used, including the apolipoprotein B to apolipoprotein AI ratio. Interpretation For people choosing to start pharmacological prophylaxis, reduction in both LDL cholesterol and hsCRP are indicators of successful treatment with rosuvastatin. Funding AstraZeneca.
Phytosterol (PS) consumption is associated with lower total and LDL-cholesterol (LDL-c) concentrations, but its impact on cardiovascular risk is unclear. This study assessed the effect of usual ...intake of PS on markers of subclinical atherosclerosis in the Longitudinal Study of Adult Health (ELSA-Brasil).
This cross-sectional study included 2560 participants of ELSA-Brasil, aged 48 (43–54) years, with available food frequency questionnaires (FFQ), coronary artery calcium (CAC) scores, carotid intima media thickness (cIMT), and carotid-femoral pulse wave velocity (cf-PWV), at baseline. Several logistic and linear regression models were used, and significance level was set at a P < 0.05. Mean values (SD) for PS consumption were 256 (198) mg/day, CAC 22.78 (110.54) Agatston Units, cf-PWV 9.07 (1.60) m/s and cIMT 0.57 (0.12) mm. PS consumption in Q4 was associated with lower total- and LDL-c levels, and with higher percentiles of cf-PWV (P < 0.001). Proportion of subjects in Q4 of PS consumption was 1.5 times higher among individuals in cf-PWV Q4, than in Q1 (P = 0.002, for comparisons among quartiles). There was a trend (P = 0.003) for higher cf-PWV with higher PS intake. In crude logistic and linear regressions, PS intake was associated with cf-PWV. In the adjusted models, these associations disappeared. No associations were found between PS and cIMT or CAC.
In this large and apparently healthy cross-sectional sample from ELSA-Brasil, usual PS consumption was associated with lower total- and LDL-cholesterol, but not with markers of subclinical atherosclerosis.
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•Phytosterol (PS) consumption is associated with lower total and LDL-cholesterol (LDL-c).•To date, the impact of usual consumption of PS on atherosclerosis is unclear.•In this large cross-sectional study higher PS consumption was not associated with subclinical atherosclerosis.
Background Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of ...combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles. Methods Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions. Results Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size. Conclusions The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374.
Monocytes circulate in the blood and migrate to inflammatory tissues, but their functions can be either detrimental or beneficial, depending on their phenotypes. In humans, classical monocytes are ...inflammatory cluster of differentiation (CD)14
CD16
CCR2
cells originated from the bone marrow or spleen reservoirs and comprise ≥92% of monocytes. Intermediate monocytes (CD14
CD16
CCR2
) are involved in the production of anti-inflammatory cytokines such as interleukin (IL)-10, reactive oxygen species (ROS), and proinflammatory mediators such as tumor necrosis factor-α (TNF-α) and IL-1β). Nonclassical monocytes (CD14
CD16
CCR2
) are patrolling cells involved in tissue repair and debris removal from the vasculature. Many studies in both humans and animals have shown the importance of monocyte chemoattractant protein-1 (MCP-1) and its receptor chemokine receptor of MCP-1 (CCR2) in pathologies, such as atherosclerosis and myocardial infarction (MI). This review presents the importance of these monocyte subsets in cardiovascular diseases (CVDs), and sheds light on new strategies for the blocking of the MCP-1/CCR2 axis as a therapeutic goal for treating vascular disorders.
Diabetes mellitus is a global epidemic, characterised as a heterogeneous group of metabolic disorders associated with high risk of CVD. Green banana biomass, which is composed of resistant starches ...(RS) and cannot be hydrolysed by amylases, delays gastric emptying and modulates insulin sensitivity, thus contributing to improve metabolic disorders. The aim of the present study was to investigate the effects of consumption of RS from green banana biomass on body composition, fasting plasma glucose, glycated Hb (HbA1c) and homeostasis model assessment of insulin resistance in subjects with pre-diabetes or type 2 diabetes on top of treatment. Middle-aged subjects (n 113) of both sexes with pre-diabetes (HbA1c: 5·7-6·4 %) or diabetes (HbA1c ≥ 6·5 %) were randomised to receive nutritional support plus green banana biomass (40 g) (RS: approximately 4·5 g, G1, n 62) or diet alone (G2, n 51) for 24 weeks. Body composition, biochemical analyses and dietary intake were evaluated at the beginning and end of the study. In the experimental group (G1), consumption of RS was associated with reduction in HbA1c (P = 0·0001), fasting glucose (P = 0·021), diastolic blood pressure (P = 0·010), body weight (P = 0·002), BMI (P = 0·006), waist and hip circumferences (P < 0·01), fat mass percentage (P = 0·001) and increase in lean mass percentage (P = 0·011). In controls (G2), reductions were observed in waist and hip circumferences (P < 0·01), HbA1c (P = 0·002) and high-density lipoprotein-cholesterol (P = 0·020). In pre-diabetes or diabetes, non-significant differences were observed in the percentage reduction in HbA1c and fasting glucose in exploratory analyses. Our results indicate that the consumption of bioactive starches is a good dietary strategy to improve metabolic control and body composition.
There is little research in the efficacy and safety of a pharmaco-invasive strategy (PIS) in patients ≥75 years versus <75 years of age. We aimed to evaluate and compare the influence of advanced age ...on the risk of death and major adverse cardiac events (MACE) in patients undergoing PIS.
Between January 2010 and November 2016, 14 municipal emergency rooms in São Paulo, Brazil, used full-dose tenecteplase to treat patients with STEMI as part of a pharmaco-invasive strategy for a local network implementation.
A total of 1852 patients undergoing PIS were evaluated, of which 160 (9%) were ≥75 years of age. Compared to patients <75 years, those ≥75 years were more often female, had lower body mass index, higher rates of hypertension; higher incidence of hypothyroidism, chronic renal failure, prior stroke, and diabetes. Compared to patients <75 years of age, in-hospital MACE and mortality were higher in patients with ≥75 years (6.5% versus 19.4%; p<0.001; and 4.0% versus 18.2%; p<0.001, respectively). Patients ≥75 years had higher rates of in-hospital major bleeding (2.7% versus 5.6%; p=0.04) and higher incidence of cardiogenic shock (7.0% versus 19.6%; p<0.001). By multivariable analysis, age ≥75 years was independent predictor of MACE (OR 3.57, 95% CI 1.72 to 7.42, p=0.001) and death (OR 2.07, 95% CI 1.12-3.82, p=0.020).
In patients with ST-segment elevation myocardial infarction undergoing PIS, age ≥75 years was an independent factor that entailed a 3.5-fold higher MACE and 2-fold higher mortality rate compared to patients <75 years of age.
Objectives The aim of this study was to evaluate the effect of statin treatment in primary prevention of cardiovascular events in different race/ethnic groups. Background Clinical trial evidence ...about the efficacy of statins in the primary prevention of cardiovascular events among nonwhites is uncertain. Methods JUPITER trial, a randomized, double-blind, placebo-controlled evaluation of rosuvastatin 20 mg in the primary prevention of myocardial infarction (MI), stroke, arterial revascularization, hospitalization for unstable angina, and cardiovascular death included 12,683 whites and 5,117 nonwhites with low-density lipoprotein levels <130 mg/dL and high-sensitivity C-reactive protein levels ≥2.0 mg/L. Results Random allocation to rosuvastatin resulted in a 45% reduction in the primary end point among whites (hazard ratio HR 0.55, 95% CI 0.43-0.69) and a 37% reduction among nonwhites (HR 0.63, 95% CI 0.41-0.99). Blacks (HR 0.65, 95% CI 0.35-1.22) and Hispanics (HR 0.58, 95% CI 0.25-1.39) had similar risk reductions. Among nonwhites in the placebo group, the stroke rate exceeded the MI rate (0.44 vs 0.20 per 100 person-years); an opposite pattern was observed among whites (0.31 vs 0.42 per 100 person-years). Nonwhites had higher death rates than whites (2.25 vs 0.93 per 100 person-years); however, all-cause mortality was similar at 20% with rosuvastatin treatment in both participant groups. Conclusions When used in primary prevention among individuals with low-density lipoprotein <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L, rosuvastatin significantly reduced first MI, stroke, arterial revascularization, hospitalization for unstable angina, and cardiovascular death among whites and nonwhites.
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