Is it time to treat prehypertension?

Prehypertension, defined as blood pressure between 120-139/80-89 mmHg, is a major public health concern. The condition is very prevalent (30% of the adult population), is often associated with other cardiovascular risk factors and independently increases the risk of hypertension and subsequent cardiovascular events. The mechanism of elevated risk for cardiovascular events associated with prehypertension is presumed to be the same as that of hypertension. In the general population, prehypertension can be lowered by lifestyle modifications, but often not reliably. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) recommendation for prehypertension management with optimal weight control (largely through diet and exercise) remains the mainstay, except for individuals with diabetes, chronic kidney disease, and perhaps known coronary artery disease, because of the shot-term cost considerations and unproven long-term prognosis. The recently published Trial of Preventing Hypertension (TROPHY) is the first study of pharmacologic intervention among those with prehypertension. Results from this trial demonstrated that angiotensin receptor blockade (ARB) retards age-related blood pressure increases in prehypertensive patients. In this review, we discuss the options for pharmacologic intervention of prehypertension, with a focus on the TROPHY trial results.

Masked hypertension definition, impact, outcomes: a critical review.

The phenomenon of masked hypertension (MH) is defined as a clinical condition in which a patient's office blood pressure (BP) level is <140/90 mm Hg but ambulatory or home BP readings are in the hypertensive range. The prevalence in the population is about the same as that of isolated office hypertension; about 1 in 7 or 8 persons with a normal office BP level may fall into this category. The high prevalence of MH would suggest the necessity for measuring out-of-office BP in persons with apparently normal or well-controlled office BP. Reactivity to daily life stressors and behavioral factors such as smoking, alcohol use, contraceptive use in women, and sedentary habits can selectively influence MH. MH should be searched for in individuals who are at increased risk for cardiovascular complications including patients with kidney disease or diabetes. Individuals with MH have been shown to have a greater-than-normal prevalence of organ damage, particularly with an increased prevalence of metabolic risk factors, left ventricular mass index, carotid intima-media thickness, and impaired large artery distensibility compared with patients with a truly normal BP level in and out of the clinic or office. Also, outcome studies have suggested that MH increases cardiovascular risk, which appears to be close to that of in-office and out-of-office hypertension. The aim of this review was to define the entity of MH, to describe its prevalence in the general population, and to discuss its correlation with cardiovascular events.

Risk of hypertensive disorders in pregnancy following assisted reproductive technology: overview and meta-analysis.

The extent of the increased risk of pregnancy hypertensive disorders following assisted reproductive technology (ART) was investigated. PubMed and the Cochrane Collaboration Library were used as data sources to identify and select longitudinal cohorts comparing pregnancies following ART with spontaneously conceived pregnancies, between 1978 and June 2016. Risk ratios and 95% confidence intervals (CIs) of three outcomes, ie, gestational hypertension (GH), preeclampsia (PE), and their sum (PHD), were calculated. Stratification of results by gestation order (singletons and nonsingletons) was pursued, but a separate "all orders" mixed stratification was considered. Sixty-six longitudinal studies (7 038 029 pregnancies; 203 375 following any ART) were eligible. All outcomes independent of gestation order ("all orders") were increased following any invasive ART: GH (+79% [95% CI, 24%-157%]) and PE (+75% [95% CI, 50%-103%]) to a greater extent, with smaller increases in PHD (+54% [95% CI, 39%-70%]). The risk of PHD following ART steadily increased independent of gestation order.

Human soluble leptin receptor concentration in healthy offspring of hypertensive parents.

Essential hypertension is associated with increased plasma leptin levels and decreased human soluble leptin receptor (hsLR) concentration. The aim of this study was to determine whether the concentration of hsLR differs among offspring of hypertensive compared with nonhypertensive parents. Subjects in the 2 groups were matched for age, sex, and body mass index. Forty-six (24 male, 22 female; mean age, 18+/-3 years; body mass index, 22.4+/-1.4 kg/m2) healthy offspring of hypertensive parents (group A) and 50 (28 male, 22 female; mean age, 18+/-3.2 years; body mass index, 22.6+/-1.7 kg/m2) healthy offspring of healthy parents (group B) were studied. The hsLR concentration (enzyme-linked immunosorbent assay method) and leptin plasma levels (radioimmunoassay method) were determined in the study population. Plasma leptin levels were significantly higher (10+/-5 vs 6+/-3 ng/mL; P<.001), while hsLR concentration was significantly lower (20+/-7 vs 29+/-8 U/mL; P<.001) in group A compared with group B. Our findings suggest that offspring of hypertensive parents have significantly higher plasma leptin levels and significantly lower hsLR concentrations compared with healthy offspring of healthy normotensive parents. Further studies are needed to determine the clinical significance of these observations.

The Tree of Sirtuins and the Garden of Cardiovascular Youth.

Sirtuins (SIRTs) are a class of nicotine adenine dinucleotide (NAD+)-dependent proteins which participate in numerous molecular pathways involved in various age-related human diseases, such as type II diabetes, cardiovascular (CV) diseases and cancer. They have a major role in apoptosis, inflammation, oxidative stress and metabolism regulation, traits that have a great impact on CV physiology and pathology. Their unique profile of NAD+ energy dependency makes them an appealing target for human intervention in cellular and metabolic processes. This review focuses on the recent advances of SIRTs research aiming to shed light on the emerging roles of SIRTs in the pathophysiology of CV and metabolic diseases.

Human soluble leptin receptor number in healthy normotensive individuals with high normal blood pressure.

BACKGROUND: High normal blood pressure (BP) seems to be related to increased cardiovascular risk in healthy normotensive subjects, whereas hyperleptinemia enhances both sympathetic tone and arterial BP. The aim of our study was to determine the human soluble leptin receptor number in healthy normotensive subjects with high normal BP and to compare these findings to those of healthy normotensive individuals with normal BP levels. METHODS: We studied 36 healthy normotensive individuals with high normal BP (19 men and 17 women, mean age 42+/-8 years, body mass index [BMI] 23+/-1.5 kg/m2) and 40 healthy normotensive individuals with normal BP (23 men and 17 women, mean age 43+/-7 years, BMI 23.2+/-1.4 kg/m2). The two groups are matched for age, sex, and BMI. The human soluble leptin receptor number and immunoreactive leptin levels were determined in the study population by enzyme-linked immunoassay and radioimmunoassay, respectively. RESULTS: Mean plasma leptin levels were significantly higher, whereas mean human soluble leptin receptor numbers were lower in the group with high normal BP compared with the normotensive group (10+/-4.8 v 6+/-2.7 ng/mL, P<.001 and 18+/-7 v 27+/-9 IU/mL, P<.001, respectively). CONCLUSIONS: Our findings indicate that normotensive individuals with high normal BP have statistically significantly higher plasma leptin levels and lower numbers of human soluble leptin receptors. This observation may play a important role in the pathogenesis of cardiovascular events in this special group of patients and needs further investigation.

Changes in metalloproteinases in healthy normotensive patients with high-normal blood pressure.

INTRODUCTION: High-normal blood pressure (HNBP) seems to be related to increased cardiovascular risk in healthy, normotensive subjects, while essential hypertension is associated with an increase in extracellular matrix content, especially fibrillar collagen type I. The aim of our study was to investigate whether collagen degradation is altered in healthy normotensives with HNBP, and whether this alteration could be related to disturbances in the matrix metalloproteinases plasma concentration, and to compare the findings to those of healthy normotensives with normal blood pressure (NBP) levels, matched for age, sex and BMI. METHODS: Twenty six (14 males, 12 females) healthy, normotensive patients with HNBP, mean age 52 +/- 5 yrs, and BMI 23 +/- 1.5 kg/m(2) (group A), and 24, healthy normotensive patients (13 males, 11 females) with NBP, mean age 53 +/- 6 yrs, and BMI 23.2 +/- 1.4 kg/m(2) (group B), were studied. The two groups were matched for age, sex and BMI. Plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors (TIMP-1) and (TIMP-4) were determined by relevant ELISA in the study population. RESULTS: Plasma MMP-9 levels were significantly higher, while TIMP-1 and TIMP-4 levels were significantly lower in group A compared to group B, (MMP-9 579 +/- 147 versus 294 +/- 111 ng/mL, TIMP-1 178 +/- 45 versus 237 +/- 35 ng/mL p < 0.01, and TIMP-4 2.2 +/- 1.4 versus 4.4 +/- 2.1 p < 0.04 respectively). CONCLUSIONS: Our findings suggest that healthy normotensives with high-normal blood pressure have significantly increased MMP-9 and decreased TIMP-1 and TIMP-4 plasma levels compared to healthy normotensives with normal blood pressure. These findings need further investigation.

Adiponectin and resistin plasma levels in healthy individuals with prehypertension.

Prehypertension seems to be related to increased cardiovascular risk in healthy subjects, while hypoadiponectinemia and hyperresistinemia may contribute to insulin resistance and accelerated atherogenesis. This study investigated whether plasma levels of adiponectin (known to increase insulin sensitivity) and resistin (a protein possibly involved in inflammatory activities) are affected in healthy individuals with prehypertension, and to compare the findings to those of healthy normotensives matched for age, gender, and body mass index. Twenty-six (14 men and 12 women) healthy individuals with prehypertension (mean age, 52+/-5 years; mean body mass index, 23+/-1.5 kg/m2) and 24 healthy normotensives (13 men and 11 women; mean age 53+/-6 years; body mass index 23.2+/-1.4 kg/m2) were studied. The adiponectin and resistin plasma levels were determined by the enzyme-linked immunosorbent assay method. Plasma resistin levels were significantly higher, while adiponectin plasma levels were significantly lower, in prehypertensive subjects compared with normotensive subjects (10.62+/-3.17 ng/mL vs. 6.72+/-3.15 ng/mL and 6.26+/-2.18 mg/mL vs. 12.12+/-4.8 mg/mL; p < 0.01, respectively). The findings suggest that healthy individuals with prehypertension have significantly higher resistin plasma levels and significantly lower adiponectin plasma levels compared with healthy normotensives. These findings may represent another possible mechanism that may increase the cardiovascular risk in this special group of patients, needing further investigation.

Parental history of hypertension is associated with coagulation-fibrinolytic balance disorders.

It has been previously shown that essential hypertension (EH) is associated with coagulation-fibrinolytic balance disorders. Our study was conducted in order to investigate disturbances in coagulation-fibrinolysis in offsprings of hypertensive parents. Two groups were studied: 44 healthy normotensive individuals (17 male, 27 female, age range 12-22 years) with a documented family history of hypertension and 33 individuals (14 male, 19 female, age range 11-21 years) without a family history of essential hypertension. The following parameters were determined in both groups: plasminogen activator inhibitor-1 antigen, tissue plasminogen activator antigen, fibrinogen, fibrin degradation products, thrombomodulin, protein S antigen, protein C activity, von Willebrand factor Ag, factor VII and factor XII activity. Additionally, systolic and diastolic blood pressure, insulin levels, blood lipids and heart rate were determined. The two groups were not found to have differences with respect to age, gender, body mass index, blood lipids and insulin levels. Hypertensive offsprings had significantly higher plasma levels of plasminogen activator inhibitor-1 antigen, fibrinogen, fibrin degradation products, protein S antigen and factor XII activity, while no differences were observed to the other haemostatic variables studied. Hence, offsprings of hypertensives had significantly higher diastolic blood pressure and heart rate. In conclusion, alterations regarding blood pressure, heart rate and fibrinolytic function exist in offsprings of hypertensive parents compared to individuals without family history of hypertension.

Markers of risk in young offspring with paternal history of myocardial infarction.

Coronary heart disease clusters within families, but there may be several reasons for this phenomenon to occur. A possible way to elucidate this is to study biological relatives of affected individuals. The aim of our study was thus to compare a number of clinical, metabolic, clotting and immunologic factors between offspring with paternal history of premature myocardial infarction and controls and to propose a model which could safely allow to identify the high risk subgroup among them. Sixty-nine offspring of both sexes mean age 18.1 years old (cases) and thirty-two frequency matched relative to age and gender controls were studied. Cases compared to controls had significantly increased diastolic blood pressure levels (74.0+/-9.9 vs. 67.4+/-8.3 mmHg, P=0.002), leptin plasma levels (11.8+/-10.8 vs. 6.8+/-3 ng/ml, P=0.046) and fibrinogen, plasminogen, fibrin degradation products and plasminogen activator inhibitor-1 plasma levels (306.6+/-52.5 vs. 280.6+/-28.9 mg%, P=0.03, 97.4+/-23.5 vs. 83.6+/-15 mg%, P=0.0007, 292.0+/-148.5 vs. 219.2+/-69.4 ng/ml, P=0.036, 14.7+/-5.3 vs. 8.7+/-3.1 I.U./ml, P=0.0001, respectively), while cases had significantly decreased HDL-cholesterol serum levels (45.9+/-12.5 vs. 50.5+/-8.8 mg%, P=0.03) and protein S plasma levels (89.9+/-17.5 vs. 101.3+/-13.7%, P=0.001). Our findings suggest that offspring of affected individuals may be considered as a high risk group for cardiovascular disease.

Canagliflozin: a new hope in the antidiabetic armamentarium.

Canagliflozin-with the patent number WO2011142478A1- belongs to a novel class of antidiabetic drugs known as SGLT2 inhibitors, which has been approved by FDA in March 2013. This medication acts through the inhibition of glucose reabsorption in the kidney resulting in glucosuria and thus lowering of glucose blood levels. There are several phase III clinical ongoing trials involving this new class of medications. So far promising results have been shown. This review article summarizes current knowledge regarding the novel SGLT2 inhibitor canagliflozin and its future perspectives in the treatment of type 2 diabetes mellitus.

On target to dual block RAS?

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are thought to possess cardioprotective, cerebroprotective, and nephroprotective properties. Both classes of agents can prevent or reverse endothelial dysfunction and atherosclerosis, thereby potentially reducing the risk of cardiovascular events. Such a reduction has been shown with angiotensin-converting enzyme inhibitors in patients with coronary artery disease, but no such data are scarce with angiotensin receptor blockers (Valsartan in Acute Myocardial Infarction study). Both angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been shown to reduce damage in target organs, such as the heart and kidney, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. These drugs (especially angiotensin receptor blockers) may successfully prevent atrial fibrillation and play a protective role in metabolic syndrome. In some clinical settings, combined therapy angiotensin-converting enzyme inhibitors with angiotensin receptor blocker (double blockade of the renin-angiotensin- aldosterone system) may appear the most effective.

Impaired glucose metabolism and the exaggerated blood pressure response to exercise treadmill testing in normotensive patients.

The authors aimed to investigate the association between glucose metabolism measures and the exaggerated blood pressure response (EXBPR) to exercise testing in normotensive nondiabetic patients. One hundred and forty-two consecutive patients underwent office blood pressure (BP) measurements, 24-hour BP monitoring, echocardiography, and treadmill exercise test according to the Bruce protocol. The population was divided into 2 groups according to EXBPR at a submaximal workload level. Furthermore, blood samples were obtained for fasting glucose (FG), fasting insulin (FI), and lipid profile assessment. Measures of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR], quantitative insulin sensitivity check index [QUICKI], and McAuley index) were also estimated, and a standardized oral glucose tolerance test was performed to evaluate glucose levels at 120 minutes (G120). Patients with EXBPR (n=40; 27 men) compared with those without EXBPR (n=102; 66 men) were older by 4+/-6 years (P<.001). FG, FI, G120, HOMA-IR, QUICKI, and McAuley index differed in patients with EXBPR compared with those without EXBPR (P<.001 for all). Logistic multivariable regression models revealed that the studied glucose metabolism measures, duration of exercise, and 24-hour systolic BP remained determinants of EXBPR (P<.05 for all) after adjustment. Impaired glucose measures are significant determinants of EXBPR to exercise testing in normotensive nondiabetic patients, suggesting that impaired glucose metabolism may contribute to adverse cardiovascular prognosis including new-onset hypertension.

Association of passive smoking with masked hypertension in clinically normotensive nonsmokers.

BACKGROUND: We investigated ambulatory blood pressure (BP) levels among clinically normotensive nonsmokers exposed (PS) and not exposed (SF) to passive smoking aiming to evaluate the relative prevalence of masked hypertension (MH). METHODS: From 790 consecutive never-treated subjects who were self-referred to an outpatient hypertensive clinic, we excluded active smokers and those having a mean clinic BP >140/90 mm Hg. In the remaining population, echocardiography and routine biochemical profile assessment was performed, whereas by the implementation of additional exclusion criteria, all clinically normotensive subjects eligible to participate (i.e., 154 PS and 100 SF) underwent to ambulatory BP monitoring. RESULTS: PS with respect to SF subjects were younger, followed a less hygienic diet and consumed more alcohol (all P < 0.05). Moreover, PS in comparison with SF showed higher 24-h systolic BP, standing diastolic BP, and clinic heart rate (126 +/- 6 mm Hg vs. 122 +/- 5 mm Hg, 89 +/- 4 mm Hg vs. 84 +/- 4 mm Hg and 79 +/- 5 beats/min vs. 73 +/- 4 beats/min, respectively, P < 0.05 for all) and higher prevalence of MH (23% vs. 8%, P < 0.01). After adjustment for confounders determinants of MH remained passive smoking, weekly duration and intensity of passive smoke exposure, younger age, clinic heart rate, low physical activity score, and standing/sitting difference of diastolic BP and heart rate (P < 0.05 for all). CONCLUSIONS: MH is associated with passive smoking in a dose-related manner and low physical activity, increased heart rate and postural hemodynamic reaction may represent potential accelerators of that phenomenon.