Plant sterols and cardiovascular disease: a systematic review and meta-analysis†

The impact of increased serum concentrations of plant sterols on cardiovascular risk is unclear. We conducted a systematic review and meta-analysis aimed to investigate whether there is an association between serum concentrations of two common plant sterols (sitosterol, campesterol) and cardiovascular disease (CVD). We systematically searched the databases MEDLINE, EMBASE, and COCHRANE for studies published between January 1950 and April 2010 that reported either risk ratios (RR) of CVD in relation to serum sterol concentrations (either absolute or expressed as ratios relative to total cholesterol) or serum sterol concentrations in CVD cases and controls separately. We conducted two meta-analyses, one based on RR of CVD contrasting the upper vs. the lower third of the sterol distribution, and another based on standardized mean differences between CVD cases and controls. Summary estimates were derived by fixed and random effects meta-analysis techniques. We identified 17 studies using different designs (four case–control, five nested case–control, three cohort, five cross-sectional) involving 11 182 participants. Eight studies reported RR of CVD and 15 studies reported serum concentrations in CVD cases and controls. Funnel plots showed evidence for publication bias indicating small unpublished studies with non-significant findings. Neither of our meta-analyses suggested any relationship between serum concentrations of sitosterol and campesterol (both absolute concentrations and ratios to cholesterol) and risk of CVD. Our systematic review and meta-analysis did not reveal any evidence of an association between serum concentrations of plant sterols and risk of CVD

Abnormal aortic wall properties in women with Turner syndrome

Background Turner syndrome (TS) is associated with aortic dilatation and dissection, but the underlying process is unclear. The aim of this study was to investigate the elastic properties and composition of the aortic wall in women with TS. Methods In this cross-sectional study, 52 women with TS aged 35 ± 13 years (50% monosomy, 12 with bicuspid aortic valve [BAV] and 4 with coarctation) were investigated using carotid-femoral pulse wave velocity (CF-PWV) by echocardiography and ascending aortic distensibility (AAD) and aortic arch pulse wave velocity (AA-PWV) by magnetic resonance imaging (MRI). As control group, 13 women with BAV without TS and 48 healthy patients were included. Results Women with TS showed a higher AA-PWV (β = 1.08, confidence interval [CI]: 0.54–1.62) after correcting for age and comorbidities compared with controls. We found no significant difference in AAD and CF-PWV. In women with TS, the presence of BAV, coarctation of the aorta, or monosomy (45, X) was not associated with aortic stiffness. In addition, aortic tissue samples were investigated with routine and immunohistochemical stains in five additional women with TS who were operated. The tissue showed more compact smooth muscle cell layers with abnormal deposition and structure of elastin and diminished or absent expression of contractile proteins desmin, actin, and caldesmon, as well as the progesterone receptor. Conclusion Both aortic arch stiffness measurements on MRI and histomorphological changes point toward an inherent abnormal thoracic aortic wall in women with TS

Clusters of risk factors in metabolic syndrome and their influence on central blood pressure in a global study

The effect of metabolic syndrome (MetS) and clusters of its components on central blood pressure (CBP) has not been well characterized. We aimed to describe the effect of MetS and clusters of its components on CBP in a large population and to identify whether this effect differs in men and women. We studied 15,609 volunteers (43% women) from 10 cohorts worldwide who participated in the Metabolic syndrome and Artery REsearch Consortium. MetS was defined according to the NCEP-ATP III criteria (GHTBW, glucose, high-density lipoprotein cholesterol, triglyceride, blood pressure, waist circumference). CBP was measured noninvasively and acquired from pulse wave analysis by applanation tonometry. MetS was associated with a 50% greater odds of having higher CSBP. After controlling for age, male sex, non HDL cholesterol, diabetes mellitus, and mean arterial pressure, only specific clusters of MetS components were associated with a higher CSBP; and some of them were significant in women but not in men. We identified "risky clusters" of MetS variables associated with high CSBP. Future studies are needed to confirm they identify subjects at high risk of accelerated arterial aging and, thus, need more intensive clinical management

Evolocumab and clinical outcomes in patients with cardiovascular disease

BACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approxi - mately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 pa - tients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for un - stable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confi - dence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for base - line LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (includ - ing new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with athero - sclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets. (Funded by Amgen; FOURIER ClinicalTrials.gov number, NCT01764633.

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Peer reviewe

Impact of varying diastolic pressure fitting technique for the reservoir-wave model on wave intensity analysis

The reservoir-wave model assumes that the measured arterial pressure is made of two components: reservoir and excess. The effect of the reservoir volume should be excluded to quantify the effects of forward and backward traveling waves on blood pressure. Whilst the validity of the reservoir-wave concept is still debated, there is no consensus on the best fitting method for the calculation of the reservoir pressure waveform. Therefore, the aim of this parametric study is to examine the effects of varying the fitting technique on the calculation of reservoir and excess components of pressure and velocity waveforms. Common carotid pressure and flow velocity were measured using applanation tonometry and doppler ultrasound, respectively, in 1037 healthy humans collected randomly from the Asklepios population, aged 35 to 55 years old. Different fitting techniques to the diastolic decay of the measured arterial pressure were used to determine the asymptotic pressure decay, which in turn was used to determine the reservoir pressure waveform. The corresponding wave speed was determined using the PU-loop method, and wave intensity parameters were calculated and compared. Different fitting methods resulted in significant changes in the shape of the reservoir pressure waveform; however, its peak and time integral remained constant in this study. Although peak and integral of excess pressure, velocity components and wave intensity changed significantly with changing the diastolic decay fitting method, wave speed was not substantially modified. We conclude that wave speed, peak reservoir pressure and its time integral are independent of the diastolic pressure decay fitting techniques examined in this study. Therefore, these parameters are considered more reliable diagnostic indicators than excess pressure and velocity which are more sensitive to fitting techniques