Hypertension constitutes a major risk factor for heart failure with preserved ejection fraction (HFpEF). HFpEF is a prevalent clinical syndrome with increased cardiovascular morbidity and mortality. Specific guideline-directed medical therapy (GDMT) for HFpEF is not established due to lack of positive outcome data from randomized controlled trials (RCTs) and limitations of available studies. Although available evidence is limited, control of blood pressure (BP) is widely regarded as central to the prevention and clinical care in HFpEF. Thus, in current guidelines including the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines, blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers provides the backbone of BP-lowering therapy in hypertensive patients. Although superiority of RAS blockers has not been clearly shown in dedicated RCTs designed for HFpEF, we propose that this core drug treatment strategy is also applicable for hypertensive patients with HFpEF with the addition of some modifications. The latter apply to the use of spironolactone apart from the treatment of resistant hypertension and the use of the angiotensin receptor neprilysin inhibitor. In addition, novel agents such as sodium-glucose co-transporter-2 inhibitors, currently already indicated for high-risk patients with diabetes to reduce heart failure hospitalizations, and finerenone represent promising therapies and results from ongoing RCTs are eagerly awaited. The development of an effective and practical classification of HFpEF phenotypes and GDMT through dedicated high-quality RCTs are major unmet needs in hypertension research and calls for action.
Objective: It has been previously demonstrated that T lymphocytes may be involved in the development of hypertension and microvascular remodeling, and that circulating T effector lymphocytes may be increased in hypertension (De Ciuceis C et al, Am J Hypertens 2016 Sep 21 online printing; Itani HA et al. Hypertension 2016; 68:123–132). In particular, Th1 and Th 17 lymphocytes may contribute to the progression of hypertension and microvascular damage while TREG lymphocytes seem to be protective. However, no data is avaliable about patients with severe obesity, in which pronounced microvascular alterations were observed (De Ciuceis C et al, Hypertension 2011; 58:29–36). Design and method: We have investigated 32 severely obese patients undergoing bariatric surgery, as well as 24 normotensive lean subjects and 11 hypertensive lean subjects undergoing an election surgical intervention. No sign of local or systemic inflammation was present in any subject or patient. A peripheral blood sample was obtained before surgery for assessment of CD4+ T lymphocyte subpopulations. Lymphocyte phenotype was evaluated by flow cytometry in order to assess T-effector and T-regulatory (TREG) lymphocytes. Subsets of TREGS were defined as follows: -TREGS recent thymic emigrants (RTE), directly derived from thymus: CD31+; -TREGS naïve: CCR7+CD45RA+; -TREGS central memory (CM): CCR7+CD45RA-; -TREGS effector memory (EM): CCR7-CD45RA-; -TREGS terminal differentiated effector memory (TDEM): CCR7-CD45RA+. Results: Results are summarized in the Table (*p < 0.05, **p < 0.01, ***p < 0.001 vs. lean normotensives; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. lean hypertensives). A marked reduction of several TREG subpopolations was observed in obese patients compared with controls, together with an increased in some T-effector cells.Conclusions: TREG lymphocytes are clearly reduced in severely obese patients, possibly contributing to the development of marked microvascular alterations previously observed in such a population.
Objective : To evaluate whether a preliminary aspiration (ASP) of the cystic component and/or using spinal needles in complex thyroid nodules (CTN) could improve the adequacy of cytological sampling. Methods : Between January 2004 and December 2006, 386 consecutive patients with CTN were enrolled in this prospective investigation. Ultrasound (US) fine needle aspiration cytology (FNAC) of the solid component of the nodule (one nodule per patient) was performed using two different 25 gauge needles, with (Yale Spinal, YS) or without (Neolus, NS) a stylet, in alternate sequence on consecutive patients. In addition, a subgroup of patients presenting larger cystic component (∼50%) was submitted to total aspiration of the cystic component (ASP+) or not submitted (ASP−) before US-FNAC, in alternate sequence within each needle type group. All the samplings were performed by a single endocrinologist. Results : Adequate specimens were observed in 163 (84.5%) and 183 (94.8%) nodules investigated by NS and YS respectively. Sampling with the stylet needle was associated with an overall significant reduction of non-diagnostic specimens (15.5% vs 5.2% by NS and YS respectively, P < 0.001). The favourable result obtained with YS was independent from preliminary aspiration of the cystic component (ASP+: 14.8% vs 5.7% by NS and YS; ASP−: 16.2% vs 4.8%, not significant). A logistic regression analysis, taking into account nodule size and presence of intranodal vascularity at eco-colour evaluation of the solid component, confirmed that needle type was the only significant predictor of successful sampling (odds ratio 3.6 (95% confidence interval 1.7–7.6), P < 0.001). Conclusions : Our data show that adopting stylet needles to perform FNAC in CTN may significantly improve the percentage of adequate sampling. On the other hand, preliminary aspiration of CTN with large cystic component does not add any advantage.
Objective: It has been previously demonstrated that inflammation in adipose tissue may be implicated in vascular dysfunction (Circulation 2009; 119(12):1661–1670). A senescence-accelerated prone mouse (SAMP8) is a model of age-related cognitive decline and vascular dysfunction. Several studies demonstrated that SAMP8 suffers from increased oxidative stress and that accelerated senescence was associated with decreased eNOS and nNOS and increased oxygen radicals synthesis. Aim of the study was to investigate functional responses of small mesenteric arteries in a senescence-accelerated prone mouse (SAMP8) before and after chronic treatment with melatonin.Design and method: We investigated 7 SAMP8 and 7 SAMR1 normal controls. Mesenteric small resistance arteries were dissected and mounted on a wire myograph, according to Mulvany-Halpern technique (internal diameter about 200 μm). A concentration-response to norepinephrine (NE, from 10–9 to 10-5 Mol/l) was evaluated in vessels with intact prerivascular fat tissue (WF) and in vessels in which perivascular fat tissue was removed (NoF). Investigations were repeated in 7 SAMP8 and 7 SAMR1 after 54 weeks of chronic treatment with melatonin, an endogenous hormone with antioxidant and vasculoprotective properties. Results: In SAMR1 control mice anticontractile effect of perivascular fat was present (WF vs. NoF: ANOVA p = 0.04), while in aging SAMP8 mice the effect was less pronounced (WF vs. NoF: ANOVA p = NS) (see figure). Long-term treatment with melatonin had no effect in SAMR1 either in WF or NoF vessels, while it decreased the contractile response to norepinephrine in noF vessels of SAMP8 (ANOVA p < 0.001); the effect of melatonin treatment in WF vessels was not statistically significant. Conclusions: The anticontractile effect of perivascular fat is impaired in a senescence-accelerated prone mouse, compared with controls. A long-term treatment with melatonin seems to decrease contractile responses to norepinephrine in NOF mesenteric small arteries of SAMP8, thus restoring an anticontractile effect, probably through antioxidant mechanisms.
Arterial hypertension is frequently associated with the presence of structural alterations in small arteries. Moreover, a reduced coronary flow reserve and vasodilator capacity has been observed in essential hypertensive patients, possibly due, at least in part, to microangiopathy of small coronary vessels. The aim of the present study was to evaluate a possible relationship between subcutaneous small artery structure and coronary flow reserve or vasodilator capacity in patients with essential hypertension.A total of 20 patients with mild to moderate essential hypertension were included in the study, and underwent a biopsy of the subcutaneous fat from the gluteal region. Small arteries were dissected and mounted on a micromyograph. The media thickness, the normalized internal diameter and the media:lumen ratio (M/L) were then calculated. In addition, a transesophageal Doppler echocardiographic study, which allows the measurement of coronary flow velocity before and during maximal pharmacological vasodilatation, was performed. Coronary flow reserve (CFR) was measured as the ratio of coronary flow velocity assessed during adenosine infusion and that measured in basal conditions. From blood pressure and coronary flow velocity during adenosine infusion, minimum coronary resistance was calculated. CFR as well as minimum coronary resistance were significantly correlated to both M/L and to normalized internal diameter of subcutaneous small arteries.Our results are consistent with the hypothesis of a generalized remodelling of small arteries in the body, including the coronary circulation; this remodelling may play an important role in the reduction of coronary vasodilator capacity in patients with mild to moderate essential hypertension.
