Fosca Quarti-Trevano’s research while affiliated with Università degli Studi di Milano-Bicocca and other places

BACKGROUND Sympathetic deactivation represents a major goal of antihypertensive drug treatment. However, whether treatment normalizes the hypertension-related sympathetic cardiovascular overdrive remains uncertain. METHODS In 219 middle-aged essential hypertensives, we analyzed, along with office systolic and diastolic blood pressure (BP) and heart rate, muscle sympathetic nerve traffic (MSNA, microneurography) before and after 3-month treatment, either as monotherapy or as combination. Controls were represented by 100 age-matched normotensives. RESULTS Treatment caused, along with a small heart rate decrease, a clear BP reduction (from 160.5/95.5 to 142.3/85.0 mm Hg, P <0.01) and a significant MSNA inhibition (from 70.7±11.5 to 65.0±10.2 bursts/100 heartbeats, mean±SD, P <0.01). A similar pattern was detected in patients under monotherapy (n=81) or combination drug treatment (n=138). MSNA was significantly related to systolic BP before and during treatment but unrelated to heart rate. In treated patients achieving the lower BP (135.1/84.5 mm Hg, n=90), the MSNA reduction was greater than that detected in patients with the higher on-treatment BP (146.7/87.4 mm Hg, n=129). However, even in patients achieving a BP target <140/90 mm Hg, MSNA remained markedly higher (on average +66.4%) compared with controls. This was the case even when treated BP was <130/80 mm Hg. Data were similar for different antihypertensive drug classes. CONCLUSIONS Thus, antihypertensive treatment, even when effective in achieving BP control, fails to restore the level of normotension-related MSNA, with a persistence of the pattern of heightened sympathetic influences typical of untreated patients with hypertension. Failure of normalization may contribute to the development of the residual cardiovascular risk reported in treated hypertensives.

The European Society of Hypertension (ESH) in the guidelines document issued in 2023 made specific recommendations regarding the diagnostic and therapeutic approach for the different hypertensive phenotypes detectable in current clinical practice. The present paper will offer a critical review of these recommendations.The clinical hypertensive phenotypes of most frequent detection in current clinical practice, namely white-coat hypertension, masked hypertension, nocturnal hypertension and isolated systolic hypertension of the elderly will be reviewed. Other less common phenotypes will be also addressed. Recommendations for each clinical phenotype are made, emphasizing the need for an accurate diagnosis and treatment for specific clinical conditions, i.e. when target organ damage and/or high cardiovascular risk is detected. Areas of uncertainty related to clinical phenotypes in which pathophysiological and prognostic information are still lacking will be discussed. Future studies will allow to refine the guidelines recommendations, particularly for the clinical conditions for which pathophysiological and prognostic information are at present scanty. Graphical Abstract

Arterial hypertension is a major risk factor for cardiovascular disease. Despite treatment recommendations, including lifestyle changes and use of combination drug treatment, a consistent fraction of hypertensive patients fails to achieve adequate blood pressure targets recommended by current guidelines. In order to improve blood pressure control and to reduce cardiovascular events, renal artery denervation has been proposed as a non-pharmacological approach. Studies conducted over the years have initially produced conflicting results on the use of renal denervation and its application in routine antihypertensive treatment remains debated. However, recent trials using different devices have shown promising results in the treatment of patients with hypertension. Although long-term results are still needed to confirm the efficacy and safety of the procedure, renal denervation regarded as an useful approach in the treatment of selected patients with hypertension, including resistant and difficult-to-control hypertension.

Hypertension is a clinical condition associated with structural alterations in small, medium, and large arteries, also affecting target organs due to the mechanical effects of high blood pressure and shear stress. However, these vascular changes are also influenced by various inflammatory and neurohumoral mediators originating from the endothelium, the renin-angiotensin-aldosterone system, the neuroadrenergic system, and the perivascular fat. Specifically, chronic hypertension leads to vascular stretching, which triggers complex signaling pathways that promote vascular remodeling. The endothelium plays a crucial role in this process, as its function is impaired in hypertensive patients, leading to reduced nitric oxide-mediated vasodilation, increased vascular tone, and a proinflammatory and prothrombotic state. Along with structural changes, hypertension also triggers dynamic alterations in arterial distensibility and arterial wall properties, leading to increased arterial stiffness, which is strongly linked to cardiovascular outcomes and associated disability, as well as subsequent rehabilitation needs. Several non-invasive and highly reproducible methods are currently used to assess arterial stiffness, one of which is the cardio-ankle vascular index (CAVI). This article examines the association between arterial stiffness and high blood pressure, with a particular focus on the results of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. This study analyzes the determinants of arterial stiffness in the general population, the different hypertensive phenotypes affecting diurnal and nocturnal blood pressure profiles, and the impact of blood pressure control through antihypertensive treatment on arterial stiffness.

Background Insulin resistance (IR) and serum uric acid (SUA) are closely interconnected: SUA contributes to adversely affects the insulin signaling pathway and contributes to IR, while IR is a known predictor for the development of hyperuricemia. The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proposed as an easily obtainable marker for IR. This research aimed to investigate the interaction between IR and glomerular filtration rate (GFR)-adjusted uricemia (SUA/GFR ratio) in determining CV risk in a large population cohort study. Methods Data from 18,694 subjects were analyzed from Uric acid Right foR heArt Healt (URRAH) database. The study evaluated the association between TG/HDL-C ratio and SUA/GFR ratio, as well as their impact on the development of outcomes during the follow-up study period. The primary endpoint was CV mortality. Results After a mean follow-up of 124 ± 64 months, 2,665 (14.2%) CV deaths occurred. The incidence of fatal and non-fatal CV events increased in parallel with the increase of TG/HDL-C quintiles. TG/HDL-C ratio showed a positive association with increasing of SUA/GFR ratio, even in non-diabetic patients. Multivariate analysis showed that the TG/HDL-C ratio increases the mortality risk even after adjustment for potential confounding factors. Finally, IR and GFR-adjusted hyperuricemia showed an additive effect on CV mortality. Conclusions Both IR and SUA/GFR ratio independently predict CV mortality, regardless of age, gender, BMI, diabetes, hypertension and statin use. The joint effect of the TG/HDL-C ratio and the elevated SUA/GFR ratio was greater than the presence of each single risk factor on CV mortality. This highlights the importance of monitoring these markers to better assess cardiovascular risk.

Background The value of the association of arterial stiffness with left ventricular concentric remodelling/left ventricular hypertrophy (LVH) assessed by echocardiography, for prediction of masked hypertension defined by office and ambulatory blood pressure monitoring (ABPM) in the general population is largely undefined. We investigated this topic in the participants to the Pressioni Monitorate E Loro Associazioni (PAMELA) study. Methods The study included 272 participants (153 normotensives and 119 with masked hypertension) who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, physical examination, blood tests, office, ABPM, echocardiographic and Cardio-Ankle Vascular Index (CAVI) measurements. Results Compared to normotensive individuals, participants with masked hypertension were younger, had significantly higher office, home, mean 24-h, day-time, night-time SBP/DBP and heart rate. The likelihood of having masked hypertension, was approximately more than two-fold higher [odds ratio (OR) = 2.29, confidence interval (CI): 1.01–5.31, P = 0.04] in participants with increased CAVI and left ventricular remodelling/LVH compared to their counterparts without organ damage. This association showed a unique value in identifying masked hypertension compared to both isolated markers of organ damage (OR = 1.69, P = 0.15 for increased CAVI and OR = 0.82, P = 0.80 for left ventricular remodelling/LVH), after adjusting for age, sex, office SBP/DBP, antihypertensive treatment and diabetes. Conclusion The present study offers a new piece of evidence of the key value of looking for both vascular and cardiac organ damage to unmask MH and improve its clinical management in the general population.