-
1.
The Role of Oxidative Stress, Adhesion Molecules and Antioxidants in Preeclampsia.
Haram, K, Mortensen, JH, Myking, O, Magann, EF, Morrison, JC
Current hypertension reviews. 2019;(2):105-112
Abstract
Oxidative stress is a consequence of reduction in the antioxidant capacity and excessive production of reactive oxygen and nitrogen species (ROS). Oxidative agents, which are overproduced due to ischemic-reperfusion injury in the placenta, may overwhelm the normal antioxidant activity. This imbalance is a key feature in the pathogenesis of preeclampsia. A decrease in glutathione peroxidase (GPX) activity is associated with the synthesis of vasoconstrictive eicosanoids such as F2-isoprostanes and thromboxane, which are known to be upregulated in preeclampsia. Biochemical markers of lipid peroxidation, such as malondialdehyde and F2-isoprostane in the placenta, are also increased. Adhesion molecules participate in the pathophysiology of preeclampsia by contributing to a reduced invasion by the trophoblast and increased vascular endothelial damage. Superoxide dismutase (SOD), catalase (CAT) and GPX play important roles counteracting oxidative stress. Other antioxidant factors participate in the etiology of preeclampsia. Levels of antioxidants such as Lycopene, Coenzyme 10, as well as some vitamins, are reduced in preeclamptic gestations.
-
2.
Effects of glucose-lowering on outcome incidence in diabetes mellitus and the modulating role of blood pressure and other clinical variables: overview, meta-analysis of randomized trials.
Thomopoulos, C, Bazoukis, G, Ilias, I, Tsioufis, C, Makris, T
Journal of hypertension. 2019;(10):1939-1949
Abstract
BACKGROUND Randomized controlled trials (RCTs) of antidiabetic agents started in the 1960s. Updated meta-analyses of RCTs investigating glucose-lowering in patients with type 2 diabetes mellitus are lacking. Also, no previous attempt was made to evaluate the role of blood pressure (BP) reduction and LDL cholesterol (LDL-C) change on outcome incidence following glucose-lowering. OBJECTIVES Three main clinical questions were investigated: the extent of different outcome reductions by glucose-lowering in patients with diabetes, the proportionality of outcome reductions to glycated hemoglobin (HBA1c) reductions and whether ongoing BP and LDL-C difference in RCTs can change glucose-lowering outcome effects. METHODS PubMed between 1960 and January 2019 (any language), Cochrane Collaboration Library and previous overviews were used as data sources to identify and select all RCTs comparing the glucose-lowering drugs with placebo or less intense treatment (intentional glucose-lowering RCTs); comparing glucose-lowering drugs with placebo without glucose-lowering intention, but HBA1c difference (nonintentional glucose-lowering RCTs); enrolling type 2 diabetes mellitus patients; and reporting ongoing SBP and DBP difference. We excluded RCTs of acute care, glucose intolerance, type 1 diabetes, multiple interventions applied and glucose-lowering by lifestyle or other interventions. Risk ratios and 95% confidence intervals, of seven fatal and nonfatal outcomes and of treatment-related discontinuations were calculated (random-effects model) before and after adjustment for the ongoing BP difference, while LDL-C difference was also considered. The relationships of different outcome reductions to HBA1c reductions were investigated by meta-regressions. RESULTS A total of 25 RCTs (174 235 individuals, follow-up 3.5 years) were eligible, and the resulted ongoing SBP/DBP difference was -1.4/-0.4 mmHg. Both before and after adjustment for BP difference, glucose-lowering reduced CHD (coronary heart disease) and both composites of major cardiovascular events were reduced by a mean of 8 and 5%, respectively, while before BP-adjustment the risk of treatment-related discontinuations was increased by 26% and the risk of stroke and all-cause death was reduced by 7 and 6%, respectively. Logarithmic risk ratios were related to HBA1c reductions for the composite of CHD and stroke and for treatment-related discontinuations. Glucose-lowering had no differential outcome effects, before and after estimate adjustment for the ongoing BP difference, at different HBA1c thresholds and targets, as well as when both baseline BP and achieved BP, overall cardiovascular risk and diabetes mellitus duration were considered as dichotomous effect modifiers. Although heart failure incidence was found increased by 15% in the early glucose-lowering RCTs, this effect faded away in contemporary RCTs. LDL-C change was overall trivial and did not change glucose-lowering outcome effects. CONCLUSION Meta-analyses of all glucose-lowering RCTs involving patients with diabetes provide precise estimates of benefits for CHD and major cardiovascular events after consideration of the resulting ongoing BP difference. No benefit or harm on mortality, heart failure and stroke were noticed, while discontinuations related to adverse events because of treatment were increased following glucose-lowering. The extent of glucose-lowering is proportionally related to changes of CHD and stroke composite, and treatment-related discontinuations.
-
3.
Physiology of blood pressure relevant to managing hypertension in pregnancy.
Ngene, NC, Moodley, J
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(8):1368-1377
Abstract
PURPOSE Pregnancy causes physiological changes in maternal organ systems, and blood pressure (BP) is one of the variables affected. This review is focusing on the physiology of BP relevant to the management of hypertension in pregnancy. MATERIALS AND METHODS A detailed literature search was performed using electronic databases (including WorldCat, PubMed, MEDLINE, Google Scholar) to retrieve and review reports related to physiology of BP in pregnancy. RESULTS During pregnancy, there is vasodilation caused by mediators such as increased levels of progesterone and nitric oxide. The vasodilation leads to a reduction in vascular resistance, BP, and renal blood flow. In compensation, the following postulated events occur: activation of renin-angiotensin-aldosterone axis, resetting of osmotic threshold for thirst, and an increase in the production of vasopressin. Sodium and water conservation ensue to increase the total body water, end-diastolic volume, cardiac output, and BP. The increase in cardiac output incompletely compensates for the decreased vascular resistance, and BP therefore decreases in midpregnancy and returns to prepregnancy level toward term. CONCLUSIONS An understanding of the physiological changes in BP is essential for appropriate management of pregnancy-related hypertension.
-
4.
Research Recommendations From the National Institutes of Health Workshop on Predicting, Preventing, and Treating Preeclampsia.
Maric-Bilkan, C, Abrahams, VM, Arteaga, SS, Bourjeily, G, Conrad, KP, Catov, JM, Costantine, MM, Cox, B, Garovic, V, George, EM, et al
Hypertension (Dallas, Tex. : 1979). 2019;(4):757-766
-
5.
Effects of isometric resistance training on resting blood pressure: individual participant data meta-analysis.
Smart, NA, Way, D, Carlson, D, Millar, P, McGowan, C, Swaine, I, Baross, A, Howden, R, Ritti-Dias, R, Wiles, J, et al
Journal of hypertension. 2019;(10):1927-1938
-
-
Free full text
-
Abstract
BACKGROUND Previous meta-analyses based on aggregate group-level data report antihypertensive effects of isometric resistance training (IRT). However, individual participant data meta-analyses provide more robust effect size estimates and permit examination of demographic and clinical variables on IRT effectiveness. METHODS We conducted a systematic search and individual participant data (IPD) analysis, using both a one-step and two-step approach, of controlled trials investigating at least 3 weeks of IRT on resting systolic, diastolic and mean arterial blood pressure. RESULTS Anonymized individual participant data were provided from 12 studies (14 intervention group comparisons) involving 326 participants (52.7% medicated for hypertension); 191 assigned to IRT and 135 controls, 25.2% of participants had diagnosed coronary artery disease. IRT intensity varied (8-30% MVC) and training duration ranged from 3 to 12 weeks. The IPD (one-step) meta-analysis showed a significant treatment effect for the exercise group participants experiencing a reduction in resting SBP of -6.22 mmHg (95% CI -7.75 to -4.68; P < 0.00001); DBP of -2.78 mmHg (95% CI -3.92 to -1.65; P = 0.002); and mean arterial blood pressure (MAP) of -4.12 mmHg (95% CI -5.39 to -2.85; P < 0.00001). The two-step approach yielded similar results for change in SBP -7.35 mmHg (-8.95 to -5.75; P < 0.00001), DBP MD -3.29 mmHg (95% CI -5.12 to -1.46; P = 0.0004) and MAP MD -4.63 mmHg (95% CI -6.18 to -3.09: P < 0.00001). Sub-analysis revealed that neither clinical, medication, nor demographic participant characteristics, or exercise program features, modified the IRT treatment effect. CONCLUSION This individual patient analysis confirms a clinically meaningful and statistically significant effect of IRT on resting SBP, DBP and mean arterial blood pressure.
-
6.
The uncertain effect of menopause on blood pressure.
Tikhonoff, V, Casiglia, E, Gasparotti, F, Spinella, P
Journal of human hypertension. 2019;(6):421-428
Abstract
In affluent societies blood pressure increases with age from early life to the eighth decade with sex differences. Before middle age, lower blood pressure values are observed in women than in coeval men, whereas the reverse seems to occur thereafter. Menopause is considered the major determinant of blood pressure rise in women. If this hypothesis is well-founded, menopause can be regarded as one of the main cardiovascular risk factors, involving more than half of the human population, as well as the most ineluctable. In industrialized countries, age at menopause ranges between 50 and 52 years. The popular message is that fertile women are protected from cardiovascular risk by circulating estrogens, a privilege that is lost when postmenopausal women become not different from men from the point of view of risk factors and cardiovascular events. Nevertheless, the hypothesis that menopause or the estrogen decrease are per se associated to blood pressure increase is still under debate. Indeed, the epidemiological challenge is due to the coincidence between advancing menopause and aging, and also to the evidence that both menopause and blood pressure have common determinants such as body mass index, diet, smoking, and socio-economic class. The strongest doubt is whether menopause is a dependent or independent risk factor for high BP, i.e. whether its action on blood pressure-if any-is due directly to estrogen fall or to other indirect factors.
-
7.
Features of and preventive measures against hypertension in the young.
Kawabe, H, Azegami, T, Takeda, A, Kanda, T, Saito, I, Saruta, T, Hirose, H
Hypertension research : official journal of the Japanese Society of Hypertension. 2019;(7):935-948
-
-
Free full text
-
Abstract
The Japanese hypertension guidelines report that essential hypertension is detected in 1-3% of upper elementary and high school students during blood pressure (BP) screenings. Hypertension in these age groups is an emerging public health concern mainly attributed to the rising rate of pediatric obesity. Considering the existence of BP tracking phenomenon, early preventive education and instruction are necessary, especially for male students with moderately elevated BP showing a tendency toward obesity, despite the low prevalence of hypertension in high school students. Students with a positive family history of hypertension and those born with low birth weight need the same measures. Lifestyle habits, such as increased alcohol intake, dramatically change once students begin university; thus, early education and instruction regarding the factors influencing BP are necessary. In particular, for male students with higher BP during high school, caution regarding increased body weight is required irrespective of their level of obesity. Young adults aged <40 years should be educated about the association between body weight and hypertension. Particular caution surrounding lifestyle habits, including drinking and smoking, is warranted in male hypertensive subjects because hypertension at a young age is strongly associated with obesity. BP monitoring and the management of obesity should be considered efficient approaches to the detection and treatment of hypertension. For the lifetime prevention of hypertension, it is essential to be aware of one's health status and learn about healthy lifestyles beginning in childhood. BP measurement may be an appropriate means to achieve this goal.
-
8.
Potential Mechanisms of Sodium-Glucose Co-Transporter 2 Inhibitor-Related Cardiovascular Benefits.
Verma, S
The American journal of cardiology. 2019;:S36-S44
Abstract
The findings of recent clinical trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors produce effects beyond glucose lowering and have demonstrated beneficial cardiovascular effects that have been observed across a broad range of patients with type 2 diabetes mellitus. In particular, the cardiovascular benefit results largely from substantial and early effects of SGLT2 inhibition on cardiovascular death and hospitalization for heart failure. Recent cardiovascular outcomes trials (CVOTs) have also shown that relative risk reductions in cardiovascular outcomes were observed with SGLT2 inhibition both in patients with current and prior heart failure. Since the observed reductions of cardiovascular outcomes with SGLT2 inhibitor therapy were observed much earlier than would be expected by an anti-atherosclerotic effect, these results have led to speculation about the potential underlying pathways. Suggested mechanisms include natriuresis and osmotic diuresis; reductions in inflammation, oxidative stress, and arterial stiffness; reductions in blood pressure and body weight; and possible renoprotective effects. These effects could produce cardiovascular benefits through a range of cardiac effects, including reduction in left ventricular load, attenuation of cardiac fibrosis and inflammation, and improved myocardial energy production. Other possible mechanisms include inhibition of sodium-hydrogen exchange, increases in erythropoietin levels, and reduction in myocardial ischemia or reperfusion injury. It is likely that a range of mechanisms underlie the observed cardiovascular benefits of SGLT2 inhibitors; further elucidation of these mechanisms will be answered by ongoing research.
-
9.
Hyperkalemia and blood pressure regulation.
Mutig, K, Bachmann, S
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(Suppl 3):iii26-iii35
Abstract
Hypertension is common in the general population. Management of hypertensive patients at risk of hyperkalemia is challenging due to potential life-threatening complications such as cardiac arrest. Chronic hyperkalemia is often associated with impaired renal ability to excrete excessive potassium ions (K+). This may refer to chronic kidney disease or certain pharmacological interventions, including broadly used renin-angiotensin-aldosterone system and calcineurin inhibitors. Understanding the intrinsic mechanisms permitting kidney adaptations to hyperkalemia is critical for choosing therapeutic strategies. Valuable insights were obtained from the analysis of familial hyperkalemic hypertension (FHHt) syndrome, which became a classic model for coincidence of high blood pressure and hyperkalemia. FHHt can be caused by mutations in several genes, all of them resulting in excessive activity of with-no-lysine kinases (WNKs) in the distal nephron of the kidney. WNKs have been increasingly recognized as key signalling enzymes in the regulation of renal sodium ions (Na+) and K+ handling, enabling adaptive responses to systemic shifts of potassium homoeostasis consequent to variations in dietary potassium intake or disease. The WNK signalling pathway recruits a complex protein network mediating catalytic and non-catalytic effects of distinct WNK isoforms on relevant Na+- or K+-transporting proteins. In this review article, we summarize recent progress in understanding WNK signalling. An update of available models for renal adaptation to hyperkalemic conditions is presented. Consequences for blood pressure regulation are discussed. Pharmacological targeting of WNKs or their substrates offers promising options to manage hypertension while preventing hyperkalemia.
-
10.
Mechanisms impairing blood pressure responses to nitrite and nitrate.
Oliveira-Paula, GH, Pinheiro, LC, Tanus-Santos, JE
Nitric oxide : biology and chemistry. 2019;:35-43
Abstract
Hypertension is a multifactorial disease associated with impaired nitric oxide (NO) production and bioavailability. In this respect, restoring NO activity by using nitrite and nitrate has been considered a potential therapeutic strategy to treat hypertension. This possibility is justified by the understanding that both nitrite and nitrate may be recycled back to NO and also promote the generation of other bioactive species. This process involves a complex biological circuit known as the enterosalivary cycle of nitrate, where this anion is actively taken up by the salivary glands and converted to nitrite by nitrate-reducing bacteria in the oral cavity. Nitrite is then ingested and reduced to NO and other nitroso species under the acid conditions of the stomach, whereas reminiscent nitrite that escapes gastric reduction is absorbed systemically and can be converted into NO by nitrite-reductases in tissues. While there is no doubt that nitrite and nitrate exert antihypertensive effects, several agents can impair the blood pressure responses to these anions by disrupting the enterosalivary cycle of nitrate. These agents include dietary and smoking-derived thiocyanate, antiseptic mouthwash, proton pump inhibitors, ascorbate at high concentrations, and xanthine oxidoreductase inhibitors. In this article, we provide an overview of the physiological aspects of nitrite and nitrate bioactivation and the therapeutic potential of these anions in hypertension. We also discuss mechanisms by which agents counteracting the antihypertensive responses to nitrite and nitrate mediate their effects. These critical aspects should be taken into consideration when suggesting nitrate or nitrite-based therapies to patients.