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Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality. It is important to distinguish between pre-existing (chronic) hypertension and gestational hypertension, developing after 20 weeks of gestation and usually resolving within 6 weeks postpartum. There is a consensus that systolic blood pressure ≥ 170 or diastolic blood pressure ≥ 110 mmHg is an emergency and hospitalization is indicated. The selection of the antihypertensive drug and its route of administration depend on the expected time of delivery. The current European guidelines recommend initiating drug treatment in pregnant women with persistent elevation of blood pressure ≥ 150/95 mmHg and at values > 140/90 mmHg in women with gestational hypertension (with or without proteinuria), with pre-existing hypertension with the superimposition of gestational hypertension, and with hypertension with subclinical organ damage or symptoms at any time during pregnancy. Methyldopa, labetalol, and calcium antagonists (the most data are available for nifedipine) are the drugs of choice. The results of the CHIPS and CHAP studies are likely to reduce the threshold for initiating treatment. Women with a history of hypertensive disorders in pregnancy, particularly those with pre-eclampsia, are at high risk of developing cardiovascular disease later in life. Obstetric history should become a part of the cardiovascular risk assessment in women.

Patients with myocardial infarction and a high-sensitivity CRP level of 2 mg or more per liter were assigned to one of three canakinumab doses or placebo. The 150-mg dose, but not the 50-mg or 300-mg dose, led to a lower incidence of recurrent cardiovascular events.

Stiffening of large arteries, clinically manifesting as increased aortic pulse wave velocity (PWV), is an inevitable outcome of aging. Among other mechanisms, impaired glucose metabolism plays an important role, leading to the deposition of advanced glycation end products (AGEs). This process is counterbalanced by the circulating soluble receptor for AGEs (sRAGE). We investigated the association between arterial stiffness on one side and multiple circulating biomarkers and the degree of skin deposition of AGEs on the other. In a cross-sectional design, 867 participants based on a general population sample (Czech post-MONICA studies) were examined. PWV was measured by SphygmoCor device (AtCor Medical Ltd.), while skin AGEs were measured using a dedicated autofluorescence method (AGE Reader mu ). To quantify the circulating status of AGEs, carboxymethyl lysine (CML) and sRAGE concentrations were assessed by ELISA, along with conventional glucose metabolism indicators. When analyzing the whole sample using multiple linear or logistic regression models and after adjustment for potential covariates, a significant association with PWV was found for fasting glycemia, HbA1c, sRAGE, skin AGEs, and the skin AGE-to-sRAGE ratio. Among these parameters, stepwise models identified the strongest association for the skin AGEs and AGE-to-sRAGE ratio, and this was also true when diabetic subjects were excluded. In contrast, neither CML nor its ratio relative to sRAGE showed any association with arterial stiffness. In conclusion, skin AGEs along with their ratio relative to sRAGE were closely associated with arterial stiffness and is a better indicator of the current status of deposited AGEs than other relevant factors.

Circulating levels of soluble receptor for advanced glycation end-products (sRAGE) have been suggested to have a protective role in neutralizing advanced glycation end-products (AGEs) and their pathological effects on vessel walls. We aimed to investigate the association between the circulating concentration of sRAGE and the dynamics of arterial wall stiffening as a manifestation of vascular aging in the general population. In a prospective cohort study, we longitudinally followed 530 general-population-based subjects (subsample of Czech post-MONICA study). Aortic pulse wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE were assessed at baseline by ELISA (R&D Systems). The average ∆PWV/year significantly decreased across the sRAGE quintiles (p = 0.048), and a drop by one sRAGE quintile was associated with an ~21% increase in the relative risk of accelerated age-dependent stiffening (∆PWV/year ≥ 0.2 m/s). Subjects in the bottom quintile of sRAGE (<889.74 pg/mL) had a fully adjusted odds ratio of accelerated stiffening of 1.72 (95% CI: 1.06–2.79), p = 0.028, while those with high sRAGE concentrations (≥1695.2 pg/mL) showed the opposite effect [odds ratio 0.55 (95% CI: 0.33–0.90), p = 0.017]. In conclusion, the circulating status of sRAGE independently influenced the individual progression of arterial stiffness over time. This finding strongly supports the hypothesis that high sRAGE has a protective role against vascular aging.

Aims/hypothesisType 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk.MethodsWe developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study.ResultsThe model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10−21 and p = 9.6 × 10−31, respectively) and a 4.4-fold (p = 6.8 × 10−33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years.Conclusions/interpretationThis novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy.

Purpose of ReviewMany aspects of reproduction have been associated with increased blood pressure and impaired glucose metabolism that reveals a subsequent increased risk of cardiovascular disease. The aim of this review is to assess reproductive life factors associated with an increased risk of hypertension and cardiovascular disease, e.g., early life programming, sexual, and reproductive health in men and women.Recent FindingsImpaired fetal growth, with low birth weight adjusted for gestational age, has been found associated with hypertension in adulthood. Erectile dysfunction, currently considered an early diagnostic marker of cardiovascular disease preceding the manifestation of coronary artery disease by several years, frequently coexisting with hypertension, could also be exacerbated by some antihypertensive drugs. Male hypogonadism or subfertility are associated with increased cardiovascular risk. Hypertensive disorders in pregnancy including preeclampsia represent a major cause of maternal, fetal and neonatal morbidity, and mortality. The risk of developing preeclampsia can be substantially reduced in women at its high or moderate risk with a low dose of acetylsalicylic acid initiated from 12 weeks of gestation. An increased risk of hypertension in women following invasive-assisted reproductive technologies has been newly observed. Blood pressure elevation has been noticed following contraceptive pill use, around the menopause and in postmenopausal age. Furthermore, drug treatment of hypertension has to be considered as a factor with a potential impact on reproduction (e.g., due to teratogenic drug effects).SummaryIn summary, a deeper understanding of reproductive life effects on hypertension and metabolic abnormalities may improve prediction of future cardiovascular disease.

It has been suggested that accumulation of advanced glycation end products (AGEs) is involved in several pathophysiological processes in the vessel wall. We hypothesized that low levels of the soluble receptor for AGEs (sRAGE) might be associated with increased arterial stiffness, a manifestation of vascular ageing in the general population. Using a cross-sectional design, we analyzed 1077 subjects from the Czech post-MONICA study. The aortic pulse wave velocity (aPWV) was measured using a Sphygmocor device. sRAGE concentrations were assessed in frozen samples using enzyme-linked immunosorbent assay methods (R&D Systems). aPWV significantly (P<0.0001) increased across the sRAGE quartiles. An aPWV of 1 m s(-1) was associated with a 37% increase in the risk of low sRAGE (<918 pg ml(-1), bottom quartile; P-value=0.018). In a categorized manner, subjects in the bottom sRAGE quartile had an odds ratio of an increased aPWV (⩾9.3 m s(-1)), adjusted for all potential confounders of 2.05 (95% confidence interval: 1.26-3.32; P=0.004), but this was only the case for non-diabetic hypertensive patients. In contrast, a low sRAGE was rejected as an independent predictor of an increased aPWV in normotensive or diabetic subjects using similar regression models. In conclusion, low circulating sRAGE was independently associated with increased arterial stiffness in a general population-based sample, but this was only observed in hypertensive non-diabetic patients.

Epidemiologic studies consistently report a U-shaped curve relationship between the amount of alcohol consumption and cardiovascular disease, with consumption of ≥ three alcoholic drinks being associated with an increased risk. However, the cardioprotective effect of light and moderate alcohol consumption has been recently questioned. In the absence of a randomized trial confirming the cardioprotective effect of light or moderate alcohol consumption, an alternative method to prove the causality is Mendelian randomization using a genetic variant serving as a proxy for alcohol consumption. A Mendelian randomization analysis by Holmes et al. suggests that a reduction in alcohol intake is beneficial for cardiovascular health also in light to moderate drinkers. In a recent analysis of 83 prospective studies, alcohol consumption was roughly linearly associated with a higher risk of stroke, coronary heart disease excluding myocardial infarction, heart failure and risk of death from aortic aneurysm dissection. By contrast, increased alcohol consumption was associated with a lower risk of myocardial infarction. \"Low-risk\" alcohol consumption recommended by the National Institute of Public Health, Czech Republic, should not exceed 16 g of 100% ethanol/day for women and 24 g/day for men; at least two days a week should be alcohol free, and the dose of ethanol during binge drinking should not exceed 40 g. In practice, this means one standard drink daily for five days at most and two standard drinks at most when binge drinking. These amounts should be considered the highest acceptable limits, but alcohol consumption in general should be discouraged.

IntroductionStudy aimed to determine the occurrence of 5 thrombosis-related single-nucleotide polymorphisms (SNPs) in patients with venous thromboembolism (VTE) (n = 2630) and a control group (n = 2637) in the Czech population.MethodsThe following gene SNPs were detected in both groups: Leiden (rs6025), (rs1799963), , fibrinogen gamma' (rs2066865), (rs2289252) and (rs8176719). Statistical analysis was performed using SAS statistical software with population genetics tools.ResultsHeterozygotes for Leiden were associated with a 5.58-fold and homozygotes Leiden with a 33.46-fold increased risk of VTE. At SNP rs1799963 ( , prothrombin), only heterozygotes had a significant 3.9-fold increased risk of VTE. The findings at SNP rs2066865 (fibrinogen gamma', ) showed a 1.37-fold increased risk of VTE for heterozygotes and a 1.77-fold increased risk of VTE for homozygotes. There is also a significant 1.42-fold increase risk of VTE in the heterozygotes and a 1.80-fold increase risk of VTE in the homozygotes of the SNP rs 2289252 ( ). Further higher increases in the risk of VTE in both variants were found in patients with VTE at rs8176719 ( , non-O). It corresponds to a 2.2-fold increase in the risk of VTE in heterozygotes and a 3.5-fold increase in the risk of VTE in homozygotes.ConclusionBesides Leiden and prothrombin mutation, the study suggests that the gene polymorphisms of (rs2066865), (rs2289252) and (rs8176719) play a role as an independent heritable risk factor for VTE in the Czech population.