Incidence of new-onset hypertension before, during, and after the COVID-19 pandemic: a 7-year longitudinal cohort study in a large population.

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.

Obesity: the perfect storm for heart failure.

Obesity condition causes morphological and functional alterations involving the cardiovascular system. These can represent the substrates for different cardiovascular diseases, such as atrial fibrillation, coronary artery disease, sudden cardiac death, and heart failure (HF) with both preserved ejection fraction (EF) and reduced EF. Different pathogenetic mechanisms may help to explain the association between obesity and HF including left ventricular remodelling and epicardial fat accumulation, endothelial dysfunction, and coronary microvascular dysfunction. Multi-imaging modalities are required for appropriate recognition of subclinical systolic dysfunction typically associated with obesity, with echocardiography being the most cost-effective technique. Therapeutic approach in patients with obesity and HF is challenging, particularly regarding patients with preserved EF in which few strategies with high level of evidence are available. Weight loss is of extreme importance in patients with obesity and HF, being a primary therapeutic intervention. Sodium-glucose co-transporter-2 inhibitors have been recently introduced as a novel tool in the management of HF patients. The present review aims at analysing the most recent studies supporting pathogenesis, diagnosis, and management in patients with obesity and HF.

Incidence of type 2 diabetes before and during the COVID-19 pandemic in Naples, Italy: a longitudinal cohort study.

Background: The association of COVID-19 with the development of new-onset diabetes has been recently investigated by several groups, yielding controversial results. Population studies currently available in the literature are mostly focused on type 1 diabetes (T1D), comparing patients with a SARS-CoV-2 positive test to individuals without COVID-19, especially in paediatric populations. In this study, we sought to determine the incidence of type 2 diabetes (T2D) before and during the COVID-19 pandemic. Methods: In this longitudinal cohort study, we analysed a cohort followed up over a 6-year period using an Interrupted Time Series approach, i.e. 3-years before and 3-years during the COVID-19 pandemic. We analysed data obtained from >200,000 adults in Naples (Italy) from January 1st 2017 to December 31st 2022. In this manner, we had the opportunity to compare the incidence of newly diagnosed T2D before (2017-2019) and during (2020-2022) the COVID-19 pandemic. The key inclusion criteria were age >18-year-old and data availability for the period of observation; patients with a diagnosis of diabetes obtained before 2017 were excluded. The main outcome of the study was the new diagnosis of T2D, as defined by the International Classification of Diseases 10 (ICD-X), including prescription of antidiabetic therapies for more than 30 days. Findings: A total of 234,956 subjects were followed-up for at least 3-years before or 3-years during the COVID-19 pandemic and were included in the study; among these, 216,498 were analysed in the pre-pandemic years and 216,422 in the pandemic years. The incidence rate of T2D was 4.85 (95% CI, 4.68-5.02) per 1000 person-years in the period 2017-2019, vs 12.21 (95% CI, 11.94-12.48) per 1000 person-years in 2020-2022, with an increase of about twice and a half. Moreover, the doubling time of the number of new diagnoses of T2D estimated by unadjusted Poisson model was 97.12 (95% CI, 40.51-153.75) months in the prepandemic period vs 23.13 (95% CI, 16.02-41.59) months during the COVID-19 pandemic. Interestingly, these findings were also confirmed when examining patients with prediabetes. Interpretation: Our data from this 6-year study on more than 200,000 adult participants indicate that the incidence of T2D was significantly higher during the pandemic compared to the pre-COVID-19 phase. As a consequence, the epidemiology of the disease may change in terms of rates of outcomes as well as public health costs. COVID-19 survivors, especially patients with prediabetes, may require specific clinical programs to prevent T2D. Funding: The US National Institutes of Health (NIH: NIDDK, NHLBI, NCATS), Diabetes Action Research and Education Foundation, Weill-Caulier and Hirschl Trusts.

Achieving a Systolic Blood Pressure Below 130 mmHg Reduces the Incidence of Cardiovascular Events in Hypertensive Patients with Echocardiographic Left Ventricular Hypertrophy.

Background: Recent reports have evidenced an increased mortality rate in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) achieving systolic blood pressure (SBP) <130mmHg. However, to the best of our knowledge, the actual effects of BP reduction to the {less than or equal to}130/80mmHg target on the incidence of cardiovascular events in hypertensive patients with a diagnosis of LVH based on echocardiographic-criteria (Echo-LVH) have never been determined. Methods: In order to fill this long-standing knowledge gap, we harnessed a population of 9511 hypertensive patients, followed-up for 33.6 [IQR 7.9-72.7] months. The population was divided into six groups according to the average SBP achieved during the follow-up ({less than or equal to}130, 130-to-139, and {greater than or equal to}140mmHg) and absence/presence of Echo-LVH. The primary endpoint was a composite of fatal or non-fatal 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 BP (DBP) were comparable between patients with and without Echo-LVH. Strikingly, the rate of primary and secondary endpoints was significantly higher in patients with Echo-LVH and SBP>130mmHg, reaching the highest rate in the Echo-LVH group with SBP{greater than or equal to}140mmHg. By separate Cox multivariable regressions, after adjusting for potential confounders, both primary and secondary endpoints were significantly associated with SBP{greater than or equal to}140mmHg and Echo-LVH. Instead, DBP reduction {less than or equal to}80mmHg was associated with a significant increased rate of secondary events. Conclusions: In hypertensive patients with Echo-LVH, achieving an average in-treatment SBP target {less than or equal to}130mmHg has a beneficial prognostic impact on incidence of cardiovascular events. Significance Statement In contrast with recent reports, achieving in-treatment SBP≤130mmHg reduces the incidence of CV events in hypertensive patients with Echo-LVH. Reducing DBP≤80mmHg is instead associated with a higher rate of CV complications. By Cox multivariable regression models, adjusting for potential confounders, the rate of hard and soft CV events was significantly associated with Echo-LVH and SBP≥140mmHg. Our data indicate that therapeutic strategies in patients with Echo-LVH should aim at reducing SBP≤130mmHg paying attention to not reducing DBP≤80mmHg.

Hypertension-mediated organ damage involving multiple sites is an independent risk factor for cardiovascular events.

Aims: Chronic pressure overload determines functional and structural alterations, leading to hypertension-mediated organ damage (HMOD), affecting multiple districts. We aim at evaluating the prognostic impact of the absence vs. presence of HMOD in one or more sites and of blood pressure (BP) and metabolic control in hypertensive patients. Methods and results: The study included 7237 hypertensive patients from the Campania Salute Network Registry, followed up for 5.3 ± 4.5 years. As HMOD, we analysed the presence of left ventricular hypertrophy, carotid plaques, and chronic kidney disease (CKD-EPI ≥3 stage) and evaluated the impact of zero vs. one vs. two vs. three sites of HMOD on the occurrence of major adverse cardiovascular events (MACEs). Blood pressure control and Metabolic Score for Insulin Resistance (METS-IR) were also considered. Optimal BP control was achieved in 57.3% patients. Major adverse cardiovascular events occurred in 351 (4.8%) patients. The MACE rate in patients without HMOD was 2.7%, whereas it was 4.7, 7.9, and 9.8% in patients with one, two, and three sites with HMOD, respectively. By using Cox multivariate models, adjusted for age, BP control, mean heart rate, mean METS-IR, number of HMOD sites, and drugs, MACE was found to be significantly associated with ageing, mean METS-IR, anti-platelet therapy, and multiple sites with HMOD, whereas a negative association was found with renin-angiotensin system inhibitor drugs. Conclusion: In hypertensive patients, the risk of MACE increases with the incremental number of districts involved by HMOD, independent of BP control and despite the significant impact of metabolic dysregulation. Hypertension-mediated organ damage involving multiple sites is the deleterious consequence of hypertension and dysmetabolism but, when established, it represents an independent cardiovascular risk factor for MACE occurrence.

Normalization of ascending aorta dimension for body size influences pathophysiologic correlation in hypertensive patients: the Campania Salute Network.

AIMS: In the present study, we assessed correlates and their consistency of ascending aorta (AscAo) measurement in treated hypertensive patients. METHODS AND RESULTS: A total of 1634 patients ≥ 18 years old with available AscAo ultrasound were included. Ascending aorta was measured at end-diastole with leading edge to leading edge method, perpendicular to the long axis of the aorta in parasternal long-axis view at its maximal identifiable dimension. Correlations of AscAo and AscAo normalized for height (AscAo/HT) or body surface area (AscAo/BSA) with demographics and metabolic profile were explored. Multi-variable regression was also used to identify potential confounders influencing univariate correlations. Sensitivity analysis was performed using cardiovascular (CV) outcome. Correlations with age, estimated glomerular filtration rate, systolic blood pressure (BP), and heart rate (HR) were similar among the three aortic measures. Women exhibited smaller AscAo but larger AscAo/BSA than men with AscAo/HT offsetting the sex difference. Obesity and diabetes were associated with greater AscAo and AscAo/HT but with smaller AscAo/BSA (all P < 0.001). In multi-variable regression model, all aortic measure confirmed the sign of their relations with sex and metabolic profile independently of age, BP, and HR. In Kaplan-Mayer analysis, only dilated AscAo and AscAo/HT were significantly associated with increased risk of CV events (both P < 0.008). CONCLUSIONS: Among patients with long-standing controlled systemic hypertension, magnitude of aortic remodelling is influenced by the type of the measure adopted, with physiological consistency only for AscAo and AscAo/HT, but not for AscAo/BSA.

Long-standing hypertension leads to the development of aortic remodelling. In particular, the haemodynamic overload due to high blood pressure may contribute to the development of ascending aorta (AscAo) dilatation. With present study we analysed, in treated hypertensive patients, the spectrum of AscAo dilatation using different anthropometric criteria reporting the clinical and echocardiographic correlates: Indexing AscAo for body surface area (BSA) leads to inconsistent negative association with obesity and other metabolic abnormalities while AscAo and AscAo indexed for height present consistent pathophysiologic profile.In sensitivity analysis, AscAo and AscAo indexed for height are significantly associated with incident cardiovascular events while indexation for BSA is not, strongly suggesting the use of AscAo/BSA should be discouraged.

Ascending aorta dilatation is associated to hard cardiovascular events, follow-up from multicentric ARGO-Perspective project.

Aortic root dilatation has been proposed as hypertension-mediated organ damage (HMOD). Nevertheless, the role of the aortic root dilatation as a possible additional HMOD is still unclear since studies conducted so far are quite heterogeneous regarding the type of population analyzed, the aortic tract considered, and the type of outcomes accounted for. The aim of the present study is to assess whether the presence of aortic dilatation is associated with strong cardiovascular (CV) events (MACE: heart failure, CV death, stroke, acute coronary syndrome, myocardial revascularization) in a population of patients affected by essential hypertension. Four hundred forty-five hypertensive patients from six Italian hospitals were recruited as part of ARGO-SIIA study1. For all centers, follow-up was obtained by re-contacting all patients by telephone and through the hospital's computer system. Aortic dilatation (AAD) was defined through absolute sex-specific thresholds as in previous studies (41 mm for males, 36 mm for females). Median follow-up was 60 months. AAD was found to be associated with the occurrence of MACE (HR = 4.07 [1.81-9.17], p < 0.001). This result was confirmed after correction for main demographic characteristics such as age, sex and BSA (HR = 2.91 [1.18-7.17], p = 0.020). At penalized Cox regression, age, left atrial dilatation, left ventricular hypertrophy and AAD were identified as best predictor of MACEs and AAD resulted a significant predictor of MACEs even after correction for these confounders (HR = 2.43 [1.02-5.78], p = 0.045). The presence of AAD was found to be associated with an increased risk of MACE independently of for major confounders, including established HMODs. AAD ascending aorta dilatation, LAe left atrial enlargement, LVH left ventricular hypertrophy, MACEs major adverse cardiovascular events, SIIA Società Italiana dell'Ipertensione Arteriosa (Italian Society for Arterial Hypertension).

Left Ventricular Mechano-Energetic Efficiency Identifies an Early Impairment of Myocardial Blood Flow in Arterial Hypertension.

BACKGROUND: Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated possible relationships between positron emission tomography/computed tomography-derived myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi). METHODS: Seventy-eight hypertensive patients without flow-limiting epicardial coronary artery disease underwent echocardiography, including MEEi computation, and cardiac positron emission tomography/computed tomography with assessment of MBF/mass ratio at rest and after stress and myocardial flow reserve. The lowest MEEi tertile (MEEi<0.031 mL/s/g) was compared to the merged second and third tertiles (MEEi≥0.031). RESULTS: Patients in the lowest MEEi tertile were older, had higher systolic blood pressure and body mass index. They also had higher prevalence of LV hypertrophy, whereas lower resting and stress MBF/mass ratio. MEEi was significantly correlated with both resting (r=0.51; P<0.0001) and hyperemic (r=0.54; P<0.0001) MBF/mass ratios, whereas it was not related to myocardial flow reserve. Delta of MBF/mass ratio was lower in the lowest MEEi tertile than in the highest (P<0.0001). In separate multiple linear regression models, after adjusting for sex, systolic blood pressure, body mass index, prevalence of LV hypertrophy, left atrial volume index, and diuretic therapy, the association between LV MEEi and both hyperemic (beta coefficient=0.44; P=0.003) and resting (beta coefficient=0.35; P=0.008) MBF/mass ratio remained significant. CONCLUSIONS: In hypertensive patients without flow-limiting epicardial coronary artery disease, low values of MEEi could detect an early LV dysfunction involving an impairment of both resting and hyperemic MBF/mass ratios. MEEi has the advantage of simpler detection, cheaper costs than positron emission tomography/computed tomography, and a lack of radiation exposure. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02211365.

The therapeutic concordance approach reduces adverse drug reactions in patients with resistant hypertension.

Background: Adverse drug reactions (ADRs) remain among the leading causes of therapy-resistant hypertension (TRH) and uncontrolled blood pressure (BP). We have recently reported beneficial results in BP control in patients with TRH adopting an innovative approach, defined as therapeutic concordance, in which trained physicians and pharmacists reach a concordance with patients to make them more involved in the therapeutic decision-making process. Methods: The main scope of this study was to investigate whether the therapeutic concordance approach could lead to a reduction in ADR occurrence in TRH patients. The study was performed in a large population of hypertensive subjects of the Campania Salute Network in Italy (ClinicalTrials.gov Identifier: NCT02211365). Results: We enrolled 4,943 patients who were firstly followed-up for 77.64 ± 34.44 months, allowing us to identify 564 subjects with TRH. Then, 282 of these patients agreed to participate in an investigation to test the impact of the therapeutic concordance approach on ADRs. At the end of this investigation, which had a follow-up of 91.91 ± 54.7 months, 213 patients (75.5%) remained uncontrolled while 69 patients (24.5%, p < 0.0001) reached an optimal BP control. Strikingly, during the first follow-up, patients had complained of a total of 194 ADRs, with an occurrence rate of 68.1% and the therapeutic concordance approach significantly reduced ADRs to 72 (25.5%). Conclusion: Our findings indicate that the therapeutic concordance approach significantly reduces ADRs in TRH patients.

Therapeutic concordance improves blood pressure control in patients with resistant hypertension.

INTRODUCTION: An empathetic approach may be particularly useful in patients with therapy-resistant hypertension (TRH), defined as the failure to achieve target blood pressure (BP) despite a maximal doses of 3 antihypertensive drugs including a diuretic. However, the effects of therapeutic concordance have not been determined in hypertensive patients. METHODS: We designed a study to explore the impact of therapeutic concordance in patients with TRH, who were included in an intervention arm based on a protocol in which trained personnel periodically verified the pharmacological regimen of these patients. RESULTS: From a cohort of 5331 hypertensive patients followed-up for 77.64 ± 34.44 months, 886 subjects were found to have TRH; of these, 322 had apparent TRH (aTRH: uncontrolled office BP but optimal home BP) and 285 refused to participate in a second follow-up study, yielding a population of 279 patients with true TRH (tTRH). These tTRH patients were followed according to the therapeutic concordance protocol for 91.91 ± 54.7 months, revealing that 210 patients (75.27%) remained with uncontrolled BP (uncontrolled tTRH, Group I) while 69 patients (24.73%) reached an optimal BP control (average BP <140/90 mmHg in at least 50% of follow-up visits, Group II). Strikingly, at the end of the second follow-up, the percentage of patients displaying a decline in kidney function was significantly smaller in Group II than in Group I (8.5% vs 23.4%, p < 0.012). CONCLUSIONS: Taken together, our findings indicate for the first time that therapeutic concordance significantly improves the outcome of antihypertensive treatment in a population of patients with TRH.

From Structural to Functional Hypertension Mediated Target Organ Damage-A Long Way to Heart Failure with Preserved Ejection Fraction.

Arterial hypertension (AH) is a major risk factor for the development of heart failure (HF) which represents one of the leading causes of mortality and morbidity worldwide. The chronic hemodynamic overload induced by AH is responsible for different types of functional and morphological adaptation of the cardiovascular system, defined as hypertensive mediated target organ damage (HMOD), whose identification is of fundamental importance for diagnostic and prognostic purposes. Among HMODs, left ventricular hypertrophy (LVH), coronary microvascular dysfunction (CMVD), and subclinical systolic dysfunction have been shown to play a role in the pathogenesis of HF and represent promising therapeutic targets. Furthermore, LVH represents a strong predictor of cardiovascular events in hypertensive patients, influencing per se the development of CMVD and systolic dysfunction. Clinical evidence suggests considering LVH as a diagnostic marker for HF with preserved ejection fraction (HFpEF). Several studies have also shown that microalbuminuria, a parameter of abnormal renal function, is implicated in the development of HFpEF and in predicting the prognosis of patients with HF. The present review highlights recent evidence on the main HMOD, focusing in particular on LVH, CMD, subclinical systolic dysfunction, and microalbuminuria leading to HFpEF.

Determinants of improvement of left ventricular mechano-energetic efficiency in hypertensive patients.

Background: Arterial hypertension, especially when coexisting with other cardiovascular risk factors, could determine an imbalance between myocardial energetic demand and altered efficiency, leading to an early left ventricular (LV) systolic dysfunction, even in terms of echo-derived mechano-energetic efficiency indexed for myocardial mass (MEEi). We aim to analyse an improvement in LV MEEi, if any, in a population of hypertensive patients with a long-term follow-up and to identify clinical, metabolic and therapeutic determinants of LV MEEi amelioration. Materials and methods: In total, 7,052 hypertensive patients, followed-up for 5.3 ± 4.5 years, enrolled in the Campania Salute Network, underwent echocardiographic and clinical evaluation. LV MEEi was obtained as the ratio between stroke volume and heart rate and normalized per grams of LV mass and ΔMEEi was calculated as difference between follow-up and baseline MEEi. Patients in the highest ΔMEEi quartile (≥0.0454 mL/s/g) (group 1) were compared to the merged first, second and third quartiles (<0.0454 mL/s/g) (group 2). METS-IR (Metabolic Score for Insulin Resistance), an established index of insulin sensitivity, was also derived. Results: Patients with MEEi improvement experienced a lower rate of major cardiovascular events (p = 0.02). After excluding patients experiencing cardiovascular events, patients in group 1 were younger (p < 0.0001), less often diabetic (p = 0.001) and obese (p = 0.035). Group 1 experienced more frequently LV mass index reduction, lower occurrence of LV ejection fraction reduction, and had a better metabolic control in terms of mean METS-IR during the follow-up (all p < 0.0001). Beta-blockers were more often used in group 1 (p < 0.0001) than group 2. A logistic regression analysis showed that younger age, lower mean METS-IR values, more frequent LV mass index reduction and therapy with beta-blockers were significantly associated with LV MEEi improvement, independently of presence of diabetes and obesity. Conclusion: Metabolic control and therapy with beta-blockers could act in a synergic way, determining an improvement in LV MEEi in hypertensive patients over time, possibly confining cardiac damage and hampering progression toward heart failure.

High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients.

BACKGROUND: Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension. METHODS: To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy. RESULTS: We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C<40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C>80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes. Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients. CONCLUSIONS: Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

Effect of Immersive Virtual Reality by a Computer Assisted Rehabilitation Environment (CAREN) in Juvenile Huntington's Disease: A Case Report.

Various studies have proven the utility of immersive virtual reality (VR) as a complementary approach to conventional neurorehabilitation therapy for improving neuromuscular and cognitive outcomes in several neurological diseases. We hereby report findings from a single-case experience of a 21-year-old woman affected by juvenile Huntington's disease (HD) who underwent a targeted rehabilitative approach using an advanced Computer Assisted Rehabilitation Environment (CAREN) with a three sessions/week schedule for six months. At the end of the program, a manifested improvement was noticed in the Falls Efficacy Scale International score, in the Tinetti Scale, in the Berg Balance score and in the lower limb strength (MRC scale). Minor although tangible improvements were also noticed in some physical performance tests (10 m walking test, time up and go test). Findings reported, although preliminary, extend for the first time the usefulness of neurorehabilitation using innovative VR technologies also to juvenile HD, a condition for which common rehabilitation strategies bring only marginal physical benefits in the majority of cases. Future, controlled studies are awaited for generalizing these observations to larger populations and for clarifying whether such benefits may persist also in the long-term.

Insulin Resistance and Vitamin D Deficiency: A Link Beyond the Appearances.

Vitamin D is a steroid hormone that plays a key role in the regulation of body homeostasis, including cardiovascular function. Although the chronic deficiency of vitamin D is associated with cardiovascular risk factors, as well as with an adverse prognosis, randomized controlled trials have failed in demonstrating that dietary vitamin D supplementation could ameliorate the prognosis of patients with cardiovascular diseases, and suggested that vitamin D deficiency is the expression of the effects of other determinants of cardiovascular risk. Thus, the supplementation of vitamin D is not sufficient to improve the cardiovascular risk profile and prognosis. Insulin resistance is a complex phenomenon that plays a key role in the pathogenesis of conventional cardiovascular risk factors. Interestingly, defects of vitamin D and insulin resistance have a superimposable epidemiological distribution. According to the common view, Insulin resistance is considered the direct or indirect consequence of vitamin D deficiency. However, it is also reasonable to speculate that the deficit or the impaired action of vitamin D, in some circumstances, could be the result of the same pathogenic mechanisms responsible of insulin resistance development. In this case, vitamin D deficiency could be considered an epiphenomenon of insulin resistance. Insulin resistance is a reversible condition, being possibly ameliorated by physical activity and hypocaloric diets. Notably, both physical exercise and energy-restricted dietary regimens are associated with an increase of vitamin D levels. These findings indicate that improving insulin resistance condition is a necessary step to ameliorate vitamin D supplementation-based strategies in cardiovascular prevention.

Low mechano-energetic efficiency is associated with future left ventricular systolic dysfunction in hypertensives.

AIMS: In a hypertensive population with optimal blood pressure control with a long-term follow-up, we aimed at analysing possible predictors of left ventricular (LV) ejection fraction (LVEF) reduction, including indexed mechano-energetic efficiency (MEEi), a well-recognized echo-derived parameter of LV performance. METHODS AND RESULTS: The study population included 5673 hypertensive patients from the Campania Salute Network with a long-term follow-up, normal baseline LVEF (≥50%), and no prevalent cardiovascular (CV) disease. Patients developing LVEF impairment (LVEF < 50% or a reduction of at least 10 percentage points compared with baseline) were compared with patients with persistently normal LVEF. Optimal blood pressure control was achieved in about 80% of patients. Patients who experienced LVEF reduction were 2.41% during a long-term follow-up (mean duration 5.6 ± 3.9 years). At baseline, they were older (59.46 ± 11.58 vs. 53.40 ± 11.41, P < 0.0001) and showed higher LV mass index (53.3 ± 12.83 vs. 47.56 ± 9.58, P < 0.0001), left atrial (LA) volume index (14.4 ± 4.2 vs. 13.1 ± 2.8, P < 0.0001) and carotid intima-media thickness (1.99 ± 0.86 vs. 1.61 ± 0.73, P < 0.0001), lower MEEi (0.32 ± 0.08 vs. 0.34 ± 0.07, P = 0.037), and higher prevalence of CV events during follow-up (13.9% vs. 3%, P < 0.0001) compared with patients with persistently normal LVEF. A logistic regression analysis, performed after running univariate analyses and selecting parameters significantly associated with LVEF reduction, showed that having a CV event [odds ratio (OR) 7.57, P < 0.0001], being in the lowest MEEi quartile (OR 2.43, P = 0.003), and having a larger LA volume index (OR 1.08, P = 0.028) were all parameters independently associated with the development of LV systolic dysfunction. A further logistic regression model, performed by excluding patients experiencing CV events, demonstrated that the lowest MEEi quartile was independently associated with the evolution towards LVEF reduction (OR 2.35, P = 0.004), despite significant impact of LA volume index (OR 1.08, P = 0.023) and antiplatelet therapy (OR 1.89, P < 0.01). Receiver operating characteristic curves showed that the model including MEEi had higher accuracy than the model without MEEi in predicting LVEF reduction (areas under the curve 0.68 vs. 0.63, P = 0.046). CONCLUSIONS: Lower values of MEEi at baseline identify hypertensive patients more liable to develop LVEF reduction. In hypertensive setting, MEEi evaluation improves risk stratification for development of LV systolic dysfunction during long-term follow-up.

Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease.

BACKGROUND: Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke. OBJECTIVES: The purpose of this study was to investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke. METHODS: In a post hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression. RESULTS: After 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [95% CI: 3.1-34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [95% CI: 1.9-12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 [95% CI: 2.33-28.7], P = 0.0010). CONCLUSIONS: In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND-Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513).

Carotid Atherosclerosis Predicts Blood Pressure Control in Patients With Hypertension: The Campania Salute Network Registry.

Background The 2018 European Society of Cardiology/European Society of Hypertension arterial hypertension guidelines do not recommend routine carotid ultrasound as a tool to identify hypertension-mediated organ damage, unless clinically indicated. However, carotid plaque (CP) is a strong correlate of increased arterial stiffness, which influences blood pressure (BP) control over time. Thus, we assessed whether evidence of CP at first visit could predict BP control during follow-up. Methods and Results From the CSN (Campania Salute Network) Registry, 6684 patients with hypertension had complete carotid ultrasound examination and were categorized by the presence of CP at baseline. Optimal BP control was defined as average BP <140/90 mm Hg and <135/85 during follow-up for office and home BP, respectively. At baseline, participants with CP (n=3061) were more likely to be men, to be older, to have diabetes, and to exhibit higher systolic BP, lower diastolic BP, worse lipid profile, and higher prevalence of left ventricular hypertrophy (all P<0.0001) than patients without CP. Optimal office BP control was adjudicated in 54% with and 62% without CP (P<0.0001), and optimal home BP in 51% with and 58% without CP (P<0.01). Presence of CP was significantly associated with the reduced probability of controlled office BP during follow-up (both P<0.0001), independently of significant effect of older age, male sex, higher baseline BP values, classes of medication, and presence of left ventricular hypertrophy, and only attenuated by duration of hypertension. Conclusions Presence of CP in treated patients with hypertension is associated with suboptimal BP control during follow-up, independently of worse metabolic profile and presence of left ventricular hypertrophy.

Advanced imaging tools for evaluating cardiac morphological and functional impairment in hypertensive disease.

Arterial hypertension represents a systemic burden, and it is responsible of various morphological, functional and tissue modifications affecting the heart and the cardiovascular system. Advanced imaging techniques, such as speckle tracking and three-dimensional echocardiography, cardiac magnetic resonance, computed tomography and PET-computed tomography, are able to identify cardiovascular injury at different stages of arterial hypertension, from subclinical alterations and overt organ damage to possible complications related to pressure overload, thus giving a precious contribution for guiding timely and appropriate management and therapy, in order to improve diagnostic accuracy and prevent disease progression. The present review focuses on the peculiarity of different advanced imaging tools to provide information about different and multiple morphological and functional aspects involved in hypertensive cardiovascular injury. This evaluation emphasizes the usefulness of the emerging multiimaging approach for a comprehensive overview of arterial hypertension induced cardiovascular damage.