Hypertension and Reproduction Nilsson, Peter M.; Viigimaa, Margus; Giwercman, Aleksander ...
Current hypertension reports,
03/2020, Letnik:
22, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Purpose of Review
Many 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 Findings
Impaired 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).
Summary
In summary, a deeper understanding of reproductive life effects on hypertension and metabolic abnormalities may improve prediction of future cardiovascular disease.
It was found that glucose in the range of concentrations 12.5–100 mM stimulated Cu
2+
–mediated free radical peroxidation of low-density lipoproteins (LDL) from human blood plasma. Considering the ...kinetic parameters of LDL peroxidation we proposed that intensification of this process may be caused by formation of free radical intermediates of glucose auto-oxidation. Addition of SOD to the medium inhibited LDL oxidation, indicating the formation of superoxide anion-radicals under autoxidation of glucose. Similarly, SOD inhibited free radical peroxidation of liposomes from egg lecithin in the presence of glucose that confirms the generation of superoxide radicals under co-oxidation of unsaturated lipids and glucose. Normalization of glucose level in the blood of patients with type 2 diabetes mellitus during therapy was accompanied by a significant decrease in LDL oxidation in vivo (the decrease in primary and secondary lipoperoxidation products). The formation of superoxide anion-radicals was observed during interaction of aminoacid
l
-lysine with a product of glucose oxidative metabolism–methylglyoxal, but not with a product of lipoperoxidation malonyldialdehyde. In accordance with the foregoing the administration of sugar-lowering drug metformin, which binds and utilizes methylglyoxal, caused a stronger inhibition of LDL peroxidation in the blood of patients with diabetes mellitus, probably due to decrease in methylglyoxal-dependent generation of superoxide anion-radicals. Based on the results we set out the hypothesis about autocatalytic mechanism of free radical reactions involving natural dicarbonyls and suppose the common molecular mechanism of vascular wall injury in atherosclerosis and diabetes.
Aldosterone, through its actions on Mineralcorticosteroid Receptors (MR), controls fluid and electrolyte balance, but also exerts various direct deleterious actions on the vasculature. A number of ...aldosterone antagonists have been manufactured to reverse these effects.
A comprehensive review of the underlying mechanisms of the actions of aldosterone and its antagonists in cardiovascular disease.
The relevant studies indexed in PubMed, Scopus and Google Scholar databases, published from 2003 to May 2018 were identified and reported.
Aldosterone binds to MR, activating them as intracellular transcription factors. Moreover, aldosterone, through its actions on MR, as well as on another not fully explored class of receptors, triggers several signaling pathways that produce rapid, non-genomic actions. In the vasculature, all these changes favor the establishment of inflammation and cardiovascular dysfunction, which, in turn, lead to or exacerbate various cardiovascular diseases. Mineralcorticosteroid Antagonists (MRA) are compounds that antagonize the action of aldosterone on MR. Spironolactone was the first steroidal MRA to be commercially used. It showed beneficial clinical results, but also a number of adverse effects. The next generation of steroidal MRA, exhibited lower potency but did not induce many of these adverse reactions, due to their high selectivity for MR. The third generation of MRA compromises the newly introduced non-steroidal MRA, which have a completely different chemical structure, they induce different and more drastic changes to MR, they are much more specific and currently under clinical trials.
New MRA, which block the aldosterone induced pathways in the vasculature, hold promising results for the treatment of cardiovascular disease.
Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. ...Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man.
We expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200-500 microM). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (Ki = 27 microM). Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio 0.98, 95% confidence interval CI 0.9 to 1.05, p > 0.33) by meta-analysis of an SLC2A9 variant in six case-control studies including 11,897 participants. In a separate meta-analysis of four population studies including 11,629 participants we found no association of SLC2A9 with systolic (effect size -0.12 mm Hg, 95% CI -0.68 to 0.43, p = 0.664) or diastolic blood pressure (effect size -0.03 mm Hg, 95% CI -0.39 to 0.31, p = 0.82).
This study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. We did not find an association of the SLC2A9 gene with blood pressure in this study. Our findings suggest potential pathogenic mechanisms that could offer a new drug target for gout.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
The integration of genetic testing into eHealth applications holds great promise for the personalization of disease prevention guidelines. However, relatively little is known about the ...impact of eHealth applications on an individual's behavior.
Aim:
The aim of the pilot study was to investigate the effect of the personalized eHealth application approach to behavior change in a 1-month follow-up period on groups with previously known and unknown caffeine impacts.
Method:
We created a direct-to-consumer approach that includes providing relevant information and personalized reminders and goals on the digital device regarding the caffeine intake for two groups of individuals: the intervention group (IG) with the genetic raw data available and the control group (CG) to test the impact of the same content (article about caffeine metabolism) on participants without the genetic test. Study participants were all Estonians (
n
= 160).
Results:
The study suggests that eHealth applications work for short-term behavior change. Participants in the genetic IG tended to increase caffeine intake if they were informed about caffeine not being harmful. They reported feeling better physically and/or mentally after their behavioral change decision during the period of the study.
Conclusions:
Our pilot study revealed that eHealth applications may have a positive effect for short-term behavior change, regardless of a prior genetic test. Further studies among larger study groups are required to achieve a better understanding about behavior change of individuals in the field of personalized medicine and eHealth interventions.
Limited information is available on office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients living in central and eastern ...European countries.
In 2008, a survey on 7860 treated hypertensive patients followed by non-specialist or specialist physicians was carried out in nine central and eastern European countries (Albania, Belarus, Bosnia, Czech Republic, Latvia, Romania, Serbia, Slovakia, and Ukraine). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Patients had a mean (±SD) age of 60.1 ± 11 years, and the majority of them (83.5%) were followed by specialists. Average clinic BP was 149.3 ± 17/88.8 ± 11 mmHg. About 70% of patients displayed a very high-risk profile. Electrocardiogram was performed in 99% of patients, echocardiography in 65%, carotid ultrasound in 24%, fundoscopy in 68%, and search for microalbuminuria in 10%. Ambulatory BP monitoring was performed in about one-fifth of the recruited patients. Despite the widespread use of combination treatment (87% of the patients), office BP control (<140/90 mmHg) was achieved in 27.1% only, the corresponding control rate for ambulatory BP (<130/80 mmHg) being 35.7%. Blood pressure control was (i) variable among different countries, (ii) worse for systolic than for diastolic BP, (iii) slightly better in patients followed by specialists than by non-specialists, (iv) unrelated to patients' age, and (v) more unsatisfactory in high-risk hypertensives and in patients with coronary heart disease, stroke, or renal failure.
These data provide evidence that in central and eastern European countries office and ambulatory BP control are unsatisfactory, particularly in patients at very high CV risk, and not differ from that seen in Western Europe. They also show that assessment of subclinical organ damage is quite common, except for microalbuminuria, and that combination drug treatment is frequently used.
Arterial hypertension is a major risk factor for cardiovascular disease and affects approximately one third of the adult population worldwide. The vascular origin of erectile dysfunction is now ...widely accepted in the vast majority of cases. Erectile dysfunction is frequently encountered in patients with arterial hypertension and greatly affects their quality of life of hypertensive patients and their sexual partners. Therefore, the management of erectile dysfunction in hypertensive patients is of paramount importance. Unfortunately, erectile dysfunction remains under-reported, under-recognized, and under-treated in hypertensive patients, mainly due to the lack of familiarity with this clinical entity by treating physicians. This review aims to discuss the more frequent problems in the management of hypertensive patients with erectile dysfunction and propose ways to overcome these problems in everyday clinical practice.
The ability to identify premature arterial stiffening is of considerable value in the prevention of cardiovascular diseases. The “ageing index” (AGI), which is calculated from the second derivative ...photoplethysmographic (SDPPG) waveform, has been used as one method for arterial stiffness estimation and the evaluation of cardiovascular ageing. In this study, the new SDPPG analysis algorithm is proposed with optimal filtering and signal normalization in time. The filter parameters were optimized in order to achieve the minimal standard deviation of AGI, which gives more effective differentiation between the levels of arterial stiffness. As a result, the optimal low-pass filter edge frequency of 6 Hz and transitionband of 1 Hz were found, which facilitates AGI calculation with a standard deviation of 0.06. The study was carried out on 21 healthy subjects and 20 diabetes patients. The linear relationship (r=0.91) between each subject’s age and AGI was found, and a linear model with regression line was constructed. For diabetes patients, the mean AGI value difference from the proposed model yAGI was found to be 0.359. The difference was found between healthy and diabetes patients groups with significance level of P<0.0005.
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