Arterial blood pressure (BP) is a continuous variable, with a physiology characterized by significant variability stemming from the complex interaction among haemodynamic factors, neuronal reflexes, as well as hormonal, behavioural, and environmental stimuli. The homoeostatic response accounts for the physiologic variability in BP in normotensive individuals, which is more evident in hypertensive patients. Blood pressure variability is a complex phenomenon, which could be classified in various types: very short term (beat to beat), short term (during 24 h), mid-term (day by day), long term (5 years). Accurate measurement of BP variability represents a complex and often controversial endeavour, despite several methodological approaches are available. Albeit a prognostic significance has been demonstrated for some indicators of BP variability, the clinical significance of this measurement is still uncertain. In fact, none of the indicators presently available for BP variability, including early morning BP rise, substantially affects, and redefines, the cardiovascular risk of the hypertensive patient, over and beyond the mere BP values. Accordingly, in defining the cardiovascular risk, the focus should be on the absolute BP values, which remain the most relevant risk factor, and the one more susceptible to modification with both non-pharmacologic and pharmacologic treatment.

Background: Levothyroxine (LT4) is the recommended treatment for millions of hypothyroid patients. Current guidelines recommend that LT4 tablets be taken in a fasting state, but inability to adhere to this often leads to poor therapy compliance. Methods: A randomized, double-blind, placebo-controlled, crossover trial was conducted in previously untreated hypothyroid patients randomly assigned to receive an oral solution of LT4 either at least 30 minutes before breakfast or directly at breakfast time. Each patient completed two six-week treatment periods, with different timing of active LT4 administration: placebo before breakfast and active LT4 at breakfast, or vice versa . At the end of each period, thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) were measured. The primary endpoint was to verify any difference in serum TSH levels whether consuming liquid LT4 at breakfast or 30 minutes prior to breakfast. Results: A total of 77 patients (64 females; median age 45.4 ± 3.7 years) completed the study. No statistically significant differences in serum TSH, fT4, or fT3 levels were observed whether LT4 was taken at breakfast or 30 minutes before, in a fasting state. No significant effect from the sequence of regimens, breakfast composition, and/or concomitantly administered drugs was observed on the dose of LT4 administered, or on the post-treatment serum TSH values. Conclusions: The TICO study suggests that a liquid LT4 formulation can be ingested directly at breakfast, thus potentially improving therapeutic compliance. This observation is of considerable clinical relevance, since non-adherence to LT4 therapy requirements is more likely to cause variability in serum TSH concentrations.

Control of lipid levels is one of the most effective strategies for cardiovascular (CV) event prevention. In fact, many clinical trials have clearly demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, primarily with statins, reduces major CV events and mortality. The evidence from these trials has been useful in designing the cholesterol treatment guidelines, which are mainly aimed at preventing and managing cardiovascular disease (CVD). However, available data indicate that a large proportion of patients fail to achieve lipid goals, and this is particularly frequent in patients at high or very high CV risk. Furthermore, owing to side effects, a significant percentage of patients cannot tolerate statin treatment. Hence, researchers have focused their attention on novel LDL-C-lowering agents that act via mechanisms distinct from that of statins. Among the new compounds under investigation, the monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) seem particularly promising, having recently been shown to be well tolerated and highly effective at lowering LDL-C, with a possible effect on the occurrence of CV events. Currently, alirocumab is approved by the US Food and Drug Administration (FDA) as an adjunct to diet and maximally tolerated statin therapy for use in adults with heterozygous familial hypercholesterolemia (FH) or those with atherosclerotic CV disease who require additional LDL-C lowering; it has also been recently approved by the European Medicines Agency (EMA) for use in patients with heterozygous FH, non–familial hypercholesterolemia or mixed dyslipidemia in whom statins are ineffective or not tolerated. Evolocumab is approved by the FDA as an adjunct to diet and maximally tolerated statins for adults with hetero- and homozygous FH and those with atherosclerotic CV disease who require additional lowering of LDL-C, and by the EMA in adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet, in combination with a statin or a statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin; alone or in combination with other lipid lowering therapies in patients who are statin-intolerant, or those for whom a statin is contraindicated. Evolocumab is also indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolemia in combination with other lipid-lowering therapies.

Introduction Achieving hypertension control is beneficial regardless of age. Fixed-combination pills have the potential of increasing adherence to treatment, improving the benefit/risk ratio, and simplifying therapy, with resulting convenience especially in the elderly. Aim We examined real-world antihypertensive treatment adherence and hypertension control rates in a cohort of Italian elderly individuals, enrolled in a prospective, pragmatic awareness-raising campaign on blood pressure (BP). Methods 13196 treated hypertensive elderly (mean age 73.2±7.5 years, 55.5% women) were recruited through opportunistic sampling, answered a brief questionnaire on antihypertensive therapy, and were followed-up for 6 months, when BP was measured as per routine care. Controlled hypertension was defined as BP < 140/90 mmHg. Real-world treatment adherence and hypertension control rates were evaluated at 6 months according to different treatment patterns (fixed-dose versus free combinations), using Yates correction for continuity to assess likelihood estimates for differences between treatments. Results 10551 participants (80%) were on a single-pill therapy and 3445 were on a fixed combination therapy of two (24.8%) or three (1.3%) drugs. Individuals on a fixed combination therapy were more adherent to treatment than the counterparts (p < 0.001). Full adherence increased with the number of drugs/pill among single-pill users (47.5%, 68.5%, and 100% with 1, 2, or 3 drugs/pill; p < 0.001). Hypertension control rates were 70% and 65.2% (p = 0.001) according to fixed or free combinations of two drugs and 71% and 63.9% (p = 0.321) for fixed or free combinations of three drugs. Conclusions Real-world data suggest that simplified treatment strategies and use of fixed combinations improve adherence to antihypertensive therapy and BP control in the elderly.

Pheochromocytoma and paraganglioma (PPGL) are rare tumors derived from the adrenal medulla and extra-adrenal chromaffin cells. Diagnosis is often challenging due to the great variability in clinical presentation; the complexity of management due to the dangerous effects of catecholamine excess and the potentially malignant behavior require in-depth knowledge of the pathology and multidisciplinary management. Nowadays, diagnostic ability has certainly improved and guidelines and consensus documents for treatment and follow-up are available. A major impulse to the development of this knowledge has come from the new findings on the genetic and molecular characteristics of PPGLs. Germline mutation in susceptibility genes is detected in 40% of subjects, with a mutation frequency of 10–12% also in patients with sporadic presentation and genetic testing should be incorporated within clinical care. PPGL susceptibility genes include “old genes” associated with Neurofibromatosis type 1 (NF1 gene), Von Hippel Lindau syndrome (VHL gene) and Multiple Endocrine Neoplasia type 2 syndrome (RET gene), the family of SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2), and genes less frequently involved such as TMEM, MAX, and FH. Each gene has a different risk of relapse, malignancy, and other organ involvement; for mutation carriers, affected or asymptomatic, it is possible to define a tailored long-life surveillance program according to the gene involved. In addition, molecular characterization of the tumor has allowed the identification of somatic mutations in other driver genes, bringing to 70% the PPGLs for which we know the mechanisms of tumorigenesis. This has expanded the catalog of tumor driver genes, which are identifiable in up to 70% of patients Integrated genomic and transcriptomic data over the last 10 years have revealed three distinct major molecular signatures, triggered by pathogenic variants in susceptibility genes and characterized by the activation of a specific oncogenic signaling: the pseudo hypoxic, the kinase, and the Wnt signaling pathways. These molecular clusters show a different biochemical phenotype and clinical behavior; they may also represent the prerequisite for implementing customized therapy and follow-up.