Publications

2024

Santulli, Gaetano, Marco Savino, Klara Komici, Pasquale Mone, Luigi Savino, and Stanislovas S Jankauskas. (2024) 2024. “A Novel Imaging Marker for Asymptomatic Cerebrovascular Lesions in Hypertension”. American Journal of Hypertension. https://doi.org/10.1093/ajh/hpae100.
Mone, Pasquale, Leonardo Bencivenga, Gaetano Santulli, Giuseppe Rengo, Germano Guerra, and Klara Komici. (2024) 2024. “Time to Negative Conversion and Cardiopulmonary Performance in Athletes With COVID-19”. ERJ Open Research 10 (4). https://doi.org/10.1183/23120541.00090-2024.

Athletes with longer time to negative conversion for COVID-19 do not present reduction of exercise capacity. However, respiratory and ventilatory parameters are modified. https://bit.ly/3TMdrFL.

Ferrone, Marco, Michele Ciccarelli, Fahimeh Varzideh, Urna Kansakar, Germano Guerra, Federica Andrea Cerasuolo, Antonietta Buonaiuto, et al. (2024) 2024. “Endothelial MicroRNAs in INOCA Patients With Diabetes Mellitus”. Cardiovascular Diabetology 23 (1): 268. https://doi.org/10.1186/s12933-024-02331-x.

Ischemia with non-obstructive coronary artery (INOCA) is a common cause of hospital admissions, leading to negative outcomes and reduced quality of life. Central to its pathophysiology is endothelial dysfunction, which contributes to myocardial ischemia despite the absence of significant coronary artery blockage. Addressing endothelial dysfunction is essential in managing INOCA to alleviate symptoms and prevent cardiovascular events. Recent studies have identified diabetes mellitus (DM) as a significant factor exacerbating INOCA complications by promoting endothelial impairment and coronary microvascular dysfunction. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets in various biological processes, including endothelial dysfunction and cardiovascular diseases. However, research on miRNA biomarkers in INOCA patients is sparse. In this study, we examined a panel of circulating miRNAs involved in the regulation of endothelial function in INOCA patients with and without DM. We analyzed miRNA expression using RT-qPCR in a cohort of consecutive INOCA patients undergoing percutaneous coronary intervention. We detected a significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, indicating their role as biomarkers for predicting and monitoring endothelial dysfunction in INOCA patients with DM.

Lembo, Maria, Valentina Trimarco, Raffaele Izzo, Maria Virginia Manzi, Francesco Rozza, Paola Gallo, Carmine Morisco, et al. (2024) 2024. “Achieving a Systolic Blood Pressure Below 130 MmHg Reduces the Incidence of Cardiovascular Events in Hypertensive Patients With Echocardiographic Left Ventricular Hypertrophy”. The Journal of Pharmacology and Experimental Therapeutics 390 (1): 4-10. https://doi.org/10.1124/jpet.123.001952.

Background: Recent reports have evidenced an increased mortality rate in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) achieving systolic blood pressure (SBP) <130 mmHg. However, to the best of our knowledge, the actual effects of blood pressure reduction to the ≤130/80 mmHg target on the incidence of cardiovascular (CV) events have never been determined in hypertensive patients with a diagnosis of left ventricular hypertrophy based on echocardiographic criteria (Echo-LVH). Methods: To fill this long-standing knowledge gap, we harnessed a population of 9511 hypertensive patients, followed-up for 33.6 [interquartile range 7.9-72.7] months. The population was divided into six groups according to the average SBP achieved during the follow-up (≤130, 130-139, and ≥140 mmHg) and absence/presence of Echo-LVH. The primary endpoint was a composite of fatal or nonfatal myocardial infarction and stroke, sudden cardiac death, heart failure requiring hospitalization, revascularization, and carotid stenting. Secondary endpoints included atrial fibrillation and transient ischemic attack. Results: During the follow-up, achieved SBP and diastolic blood pressure (DBP) were comparable between patients with and without Echo-LVH. Strikingly, the rates of primary and secondary endpoints were significantly higher in patients with Echo-LVH and SBP >130 mmHg, reaching the highest values in the Echo-LVH group with SBP ≥140 mmHg. By separate Cox multivariable regressions, after adjusting for potential confounders, both primary and secondary endpoints were significantly associated with SBP ≥140 mmHg and Echo-LVH. Instead, DBP reduction ≤80 mmHg was associated with a significant increased rate of secondary events. Conclusions: In hypertensive patients with Echo-LVH, achieving an average in-treatment SBP target ≤130 mmHg has a beneficial prognostic impact on incidence of CV events. SIGNIFICANCE STATEMENT: Contrary to recent findings, achieving in-treatment SBP ≤130 mmHg lowers the incidence of CV events in hypertensive patients with Echo-LVH. However, reducing DBP ≤80 mmHg is linked to increased CV complications. Cox multivariable regression models, considering potential confounders, reveal that the rate of hard and soft CV events is significantly associated with Echo-LVH and SBP ≥140 mmHg. Our data indicate that therapeutic strategies for Echo-LVH patients should target SBP ≤130 mmHg while avoiding lowering DBP ≤80 mmHg.

Santulli, Gaetano, Valeria Visco, Fahimeh Varzideh, Germano Guerra, Urna Kansakar, Maurizio Gasperi, Anna Marro, et al. (2024) 2024. “Prediabetes Increases the Risk of Frailty in Prefrail Older Adults With Hypertension: Beneficial Effects of Metformin”. Hypertension (Dallas, Tex. : 1979) 81 (7): 1637-43. https://doi.org/10.1161/HYPERTENSIONAHA.124.23087.

BACKGROUND: Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals.

METHODS: We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months.

RESULTS: We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001).

CONCLUSIONS: Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.

Santulli, Gaetano, Valeria Visco, Michele Ciccarelli, Mario Nicola Vittorio Ferrante, Piero De Masi, Antonella Pansini, Nicola Virtuoso, et al. (2024) 2024. “Frail Hypertensive Older Adults With Prediabetes and Chronic Kidney Disease: Insights on Organ Damage and Cognitive Performance - Preliminary Results from the CARYATID Study”. Cardiovascular Diabetology 23 (1): 125. https://doi.org/10.1186/s12933-024-02218-x.

BACKGROUND: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR).

METHODS: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min.

RESULTS: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable.

CONCLUSIONS: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.

Trimarco, Valentina, Raffaele Izzo, Daniela Pacella, Ugo Trama, Maria Virginia Manzi, Angela Lombardi, Roberto Piccinocchi, et al. (2024) 2024. “Incidence of New-Onset Hypertension Before, During, and After the COVID-19 Pandemic: A 7-Year Longitudinal Cohort Study in a Large Population”. BMC Medicine 22 (1): 127. https://doi.org/10.1186/s12916-024-03328-9.

BACKGROUND: While the augmented incidence of diabetes after COVID-19 has been widely confirmed, controversial results are available on the risk of developing hypertension during the COVID-19 pandemic.

METHODS: We designed a longitudinal cohort study to analyze a closed cohort followed up over a 7-year period, i.e., 3 years before and 3 years during the COVID-19 pandemic, and during 2023, when the pandemic was declared to be over. We analyzed medical records of more than 200,000 adults obtained from a cooperative of primary physicians from January 1, 2017, to December 31, 2023. The main outcome was the new diagnosis of hypertension.

RESULTS: We evaluated 202,163 individuals in the pre-pandemic years and 190,743 in the pandemic years, totaling 206,857 when including 2023 data. The incidence rate of new hypertension was 2.11 (95% C.I. 2.08-2.15) per 100 person-years in the years 2017-2019, increasing to 5.20 (95% C.I. 5.14-5.26) in the period 2020-2022 (RR = 2.46), and to 6.76 (95% C.I. 6.64-6.88) in 2023. The marked difference in trends between the first and the two successive observation periods was substantiated by the fitted regression lines of two Poisson models conducted on the monthly log-incidence of hypertension.

CONCLUSIONS: We detected a significant increase in new-onset hypertension during the COVID-19 pandemic, which at the end of the observation period affected   20% of the studied cohort, a percentage higher than the diagnosis of COVID-19 infection within the same time frame. This observation suggests that increased attention to hypertension screening should not be limited to individuals who are aware of having contracted the infection but should be extended to the entire population.