Carla Sala

Background/Objectives: Although global longitudinal strain (GLS) appears more sensitive than the ejection fraction in uncovering subtle left ventricular (LV) dysfunction, evidence of impaired LV mechanics in children/adolescents with obesity, independent of comorbidities, remains limited. The aim of the present study was to provide new information on clinical and echocardiographic correlates associated with LV mechanics in normotensive children/adolescents with obesity and without comorbidities. Methods: The Pub-Med, Ovid MEDLINE, Ovid EMBASE, and Cochrane databases were searched to identify eligible studies from inception up to 31 March 2025. Studies reporting data on LV mechanics (i.e., GLS, global circumferential strain [GCS]) in children/adolescents with obesity were included. Meta-regression analyses between GLS, GCS, and several clinical, laboratory, and echocardiographic parameters were performed using a random-effect model. Results: Twenty-seven studies including 1398 normotensive children/adolescents with obesity (mean age 12.6 ± 1.8 years) were considered. There was a significant inverse relationship between GLS and body mass index (BMI) (coefficient = −0.33 ± 0.11, p = 0.003) and fat mass (coefficient = −0.19 ± 0.07, p = 0.005); this was not the case for GCS. Notably, both GLS and GCS were unrelated to several clinical/laboratory variables such as blood pressure, metabolic parameters, LV mass, and LV diastolic function indices. Conclusions: Our findings suggest that increasing BMI and fat mass are the only key factors associated with reduced longitudinal myocardial deformation in pediatric obesity. GLS, unlike GCS, can be regarded as an early marker of subclinical organ damage in this setting and should be assessed to optimize cardiovascular prevention strategies in children/adolescents with obesity regardless of hypertension or comorbidities.

Background and aim: Nitric oxide inhibits platelet aggregation by increasing the second messenger cyclic guanosine-3′,5′-monophosphate (cGMP) through the activation of soluble guanylyl cyclase in target cells. Within this context, the oxidative stress associated with the aldosterone excess impairs the nitric oxide availability. Thus, the aim of the present study was to assess the impact of chronic aldosterone excess on the platelet nitric oxide/cGMP pathway in humans. Methods: The levels of cGMP were evaluated in platelets of male patients, 12 with primary aldosteronism (PA) and 32 with uncomplicated essential hypertension (EH), matched for age and blood pressure (BP) values. Results: PA and EH patients were 52.8 ± 3 years old and 51.6 ± 1.6 years old, respectively. Systolic and diastolic BP were 158 ± 5.0 mmHg and 105.9 ± 2.3 mmHg in PA and did not differ compared to EH patients (156.6 ± 2.4 mmHg and 104.7 ± 1.2 mmHg). Mean aldosterone levels were significantly higher in PA (25.5 ± 8.8 ng/dL) compared toEH (8.11 ± 0.73 ng/dL), whereas potassium was significantly lower in PA (3.52 ± 0.18 mEq/L) compared to EH (4.08 ± 0.04 mEq/L). Aldosterone and potassium were inversely related (r = −0.49, p = 0.0006) in the whole study population (n = 44). Platelet cGMP was significantly lower in PA (5.1 ± 0.36 pM/10⁹ cells) than in EH (7.1 ± 0.53 pM/10⁹ cells), and in the entire study cohort, it was directly related to plasma potassium (r = 0.43, p = 0.0321). Conclusions: These results show an impairment of nitric oxide/cGMP signaling in platelets of PA patients. This effect is likely related to the potassium-depleting effect of chronic aldosterone excess. Future studies are needed to understand whether the platelet nitric oxide/cGMP system is involved in the atherothrombotic events in these patients.

Aim: Whether exaggerated blood pressure response (EBPR) to exercise represents a marker of masked hypertension (MH) in individuals with no prior history of hypertension is still unclear. We investigated this issue through a review and a meta-analysis of studies providing data on this association in normotensive individuals undergone both to dynamic or static exercise and to 24 h blood pressure monitoring (ABPM). Design: A systematic search was performed using Pub-Med, OVID, EMBASE, and Cochrane library databases from inception up to 31 December 2022. Studies were identified by using the following search terms: “masked hypertension”, “out-of-office hypertension”, “exercise blood pressure”, “exaggerated blood pressure exercise”, “exercise hypertension”. Results: Nine studies including a total of 387 participants with MH and 406 true normotensive controls were considered. Systolic BP (SBP) and diastolic BP (DBP) at rest were significantly higher in MH individuals than in sustained normotensives: 126.4 ± 1.4/78.5 ± 1.8 versus 124.0 ± 1.4/76.3 ± 1.3 mmHg (SMD: 0.21 ± 0.08, CI: 0.06–0.37, p = 0.007 for SBP; 0.24 ± 0.07, CI: 0.08–0.39, p = 0.002 for DBP). The same was true for BP values at peak exercise: 190.0 ± 9.5/96.8 ± 3.7 versus 173.3 ± 11.0/88.5 ± 1.8 mmHg (SMD 1.02 ± 0.32, CI: 0.39–1.65, p = 0.002 for SBP and 0.97 ± 0.25, CI: 0.47–1.96, p < 0.0001 for DBP). The likelihood of having an EBPR was significantly greater in MH than in their normotensive counterparts (OR: 3.33, CI: 1.83–6.03, p < 0.0001). Conclusions: Our meta-analysis suggests that EBPR reflects an increased risk of MH and that BP measurement during physical exercise aimed to assess cardiovascular health may unmask the presence of MH. This underscores the importance of BP measured in the medical setting at rest and in dynamic conditions in order to identify individuals at high cardiovascular risk due to unrecognized hypertension.

Aim: We investigated the association between obstructive sleep apnoea (OSA) and subclinical systolic dysfunction through a meta-analysis of echocardiographic studies that provided data on left ventricular (LV) mechanics as assessed by global longitudinal strain (GLS). Design: The PubMed, OVID-MEDLINE, and Cochrane library databases were systematically analyzed to search English-language articles published from inception to 31 December 2021. Studies were detected by using the following terms: ‘obstructive sleep apnea’, ‘sleep quality’, ‘sleep disordered breathing’, ‘cardiac damage’, ‘left ventricular hypertrophy’, ‘systolic dysfunction’, ‘global longitudinal strain’, ‘left ventricular mechanics’, ‘echocardiography’ and ‘speckle tracking echocardiography’. Results: The meta-analysis included 889 patients with OSA and 364 non-OSA controls from 12 studies. Compared with controls, GLS was significantly reduced in the pooled OSA group (SMD −1.24 ± 0.17, CI: −1.58 to −0.90, P < 0.0001), as well as in the normotensive OSA subgroup (SMD: −1.17 ± 0.12 CI:−1.40 to −0.95, P < 0.0001). Similar findings were obtained in sub-analyses performed separately in mild, moderate and severe OSA. This was not the case for LV ejection fraction (LVEF) (i.e. comparisons between controls vs. mild OSA, mild vs. moderate OSA, moderate vs. severe OSA). Conclusion: GLS is impaired in patients with OSA (independently from hypertension), worsening progressively from mild to moderate and severe forms, thus allowing to identify subclinical alterations of the systolic function not captured by LVEF. Therefore, myocardial strain assessment should be implemented systematically in the OSA setting to timely detect systolic dysfunction.

Studies show that patients with elevated triglycerides and well-controlled LDL levels under statin therapy still have a significant residual risk of cardiovascular (CV) events. Despite many attempts to reduce triglycerides with different hypolipidemic drugs, no therapeutic option has given satisfactory results so far. The initial enthusiasm that omega-3 fatty acids can effectively reduce triglycerides and CV risk was replaced with skepticism when the first large clinical trials failed to show any benefit in primary or secondary prevention. However, the latest studies succeeded in showing a positive effect of omega-3 fatty acids on CV outcome in patients with hypertriglyceridemia. The largest benefit was reported in secondary but not primary prevention. Interestingly, the reduction in triglycerides in some of these studies was disproportionately low to the relatively high CV risk reduction, which could indicate some other effects of omega-3 fatty acids that go well beyond hypotriglyceridemic action. This includes blood pressure reduction, antithrombotic effect, improvement of inflammatory status, endothelial function, and insulin resistance. Investigations also reported a significant and positive influence of omega-3 fatty acids on the composition and stabilization of coronary atherosclerotic plaques in patients with and without previous CV events. In addition to insufficiently known mechanisms of action and conflicting results about the effectiveness of omega-3 fatty acids, the safety problems, which include increased prevalence of atrial fibrillation and hemorrhage, were also reported. The aim of this clinical review was to summarize the current knowledge regarding the use of omega-3 fatty acids in CV patients, particularly those with coronary artery disease, and to present an overview of key clinical trial data.

The association between pre-hypertension (pre-HTN) and abnormal left ventricular (LV) geometric patterns is unclear. We performed a meta-analysis of echocardiographic studies aimed to provide a new piece of information on LV geometric alterations in untreated pre-HTN subjects. Studies were identified by crossing the following search terms: “pre-hypertension”,“high normal blood pressure”, “heart”, “LV hypertrophy” (LVH), ‘LV geometry’, “LV mass”, echocardiography. A total 60,949 subjects (38,536 normotensive, 14,453 pre-HTN, and 7,960 HTN individuals) were included in 6 studies. LV concentric remodelling was the most common abnormal pattern in pre-HTN subjects followed by eccentric and concentric LVH. Compared to normotensive group, pre-HTN exhibited a higher risk of LV concentric remodelling (OR: 1.89, CI:1.70–2.10, p < 0.001), eccentric LVH (OR: 1.65, CI: 1.40–1.90, p < 0.001) and concentric LVH (OR: 2.09, CI 1.50–3.00, p < 0.001). The likelihood of having abnormal LV patterns in HTN was significantly higher (p < 0.001 for all) than in pre-HTN participants. Our meta-analysis shows that alterations in LV geometry in pre-HTN subjects are intermediate between normotensive and HTN individuals. These findings suggest that pre-HTN is associated to early changes in LV structure and geometry and preventive strategies may have a protective impact on development of subclinical cardiac damage in this setting.

Data on left ventricular hypertrophy (LVH) in patients with renal artery stenosis (RAS) and its regression following renal revascularization are scanty. We performed a meta-analysis to provide comprehensive information on this clinically relevant issue. Full articles providing data on: LVH, as assessed by echocardiography, in RAS patients as compared with essential hypertensive counterparts; changes of left ventricular (LV) mass index after renal artery revascularization were considered. A total of 905 study participants (RAS = 446, essential hypertensive = 459) of both sex were included in nine studies. Pooled LV mass index was higher in RAS than in essential hypertensive patients (140.4 ± 11.1 g/m2 versus 121.8 ± 6.2 g/m2, standard mean difference being 0.41 ± 0.07 [95% confidence interval (CI) 0.27–0.51, P < 0.001]. Among 360 RAS patients undergone renal revascularization from eight studies, baseline and post-intervention pooled mean LV mass index values were 129.0 ± 10.2 g/m2 and 115.5 ± 9.9 g/m2, respectively, the standard mean difference being−0.36 ± 0.06 (95% CI from −0.47 to −0.25, P < 0.001). These findings were unaffected by publication bias or single study effect. Our meta-analysis indicates that RAS patients have an increased likelihood of LVH compared with essential hypertensive counterparts and renal artery revascularization has a beneficial effect on LV structure, as reflected by a significant decrease in LV mass index.

Because subclinical alterations in cardiovascular structure reflect cumulative damage induced by risk factors and represent an intermediate stage between risk factor exposure and cardiovascular events, this damage is regarded as a marker of increased cardiovascular risk in different clinical settings, including the general population. The Pressioni Monitorate e Loro Associazioni (PAMELA) is an originally designed research study aimed at assessing the normal values and prognostic significance of ambulatory and home blood pressure in a representative sample of the Northern Italian general population. Because the study protocol included the collection of electrocardiographic (ECG) and echocardiographic (ECHO) data, the prevalence and clinical correlates, as well as the prognostic value of subclinical cardiac alterations, have been extensively investigated. This article is a review of the findings of the PAMELA study regarding the clinical aspects and prognostic significance of cardiac abnormal phenotypes such as left ventricular hypertrophy, left atrial dilatation and aortic root dilation.