Cardiorenal multimorbidity in hospitalized cardiology patients: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) study.

PURPOSE: Cardiovascular disease is commonly accompanied by renal dysfunction. Multimorbidity in hospitalized patients impacts unfavorably on prognosis and hospital stay. We aimed to illustrate the contemporary burden of cardiorenal morbidity across inpatient cardiology care in Greece. METHODS: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) used an electronic platform to collect demographic and clinically relevant information about all patients hospitalized on March 3, 2022, in Greece. The participating institutions covered all levels of inpatient cardiology care and most of the country's territories to collect a real-world, nation representative sample. RESULTS: A total of 923 patients (men 68.4%, median age 73 ± 14.8 years) were admitted to 55 different cardiology departments. 57.7% of the participants were aged >70 years. Hypertension was highly prevalent and present in 66% of the cases. History of chronic HF, diabetes mellitus, atrial fibrillation, and chronic kidney disease was present in 38%, 31.8%, 30%, and 26%, respectively. Furthermore, 64.1% of the sample exhibited at least one of these 4 entities. Accordingly, a combination of ≥2 of these morbid conditions was recorded in 38.7%, of ≥3 in 18.2%, whereas 4.3% of the sample combined all 4 in their medical history. The most common combination was the coexistence of heart failure-atrial fibrillation accounting for 20.6% of the sample. Nine of 10 nonelectively admitted patients were hospitalized due to acute HF (39.9%), acute coronary syndrome (33.5%), or tachyarrhythmias (13.2%). CONCLUSION: HECMOS participants carried a remarkable burden of cardio-reno-metabolic disease. HF in conjunction with atrial fibrillation was found to be the most prevalent combination among the studied cardiorenal nexus of morbidities in the whole study population.

Left ventricular mass versus pulse wave velocity as predictors of coronary artery disease in hypertensive patients: data from a 6-year-follow-up study.

In treated hypertensive patients, there is a substantial residual cardiovascular (CV) risk that cannot be assessed by the available prediction models. This risk can be associated with subclinical organ damage, such as increased left ventricular mass (LVM) and arterial stiffness. However, it remains unknown which of these two CV markers better predicts coronary artery disease (CAD). A prospective cohort study was used to answer the above question. The study sample consisted of 1033 patients with hypertension (mean age 55.6 years, 538 males) free of CAD at baseline, who were followed for a mean period of 6 years. At baseline, all subjects underwent a complete echocardiographic study and pulse wave velocity (PWV) measurement. Hypertensive individuals who developed CAD (2.8%) compared to those without CAD at follow-up, had a higher baseline LVM index (by 16.7 g/m2, p < 0.001), higher prevalence of left ventricular hypertrophy (LVH) (21% greater, p = 0.027) and greater prevalence of high PWV levels at baseline (21% greater, p = 0.019). Multivariate Cox regression analysis revealed that baseline age >65 years (HR = 2.067, p = 0.001), male gender (HR = 3.664, p = 0.001), baseline chronic kidney disease (HR = 2.020, p = 0.026), baseline diabetes mellitus (HR = 1.952, p = 0.015) and baseline LVH (HR = 2.124 p = 0.001) turned out to be independent predictors of CAD, whereas high PWV levels were not. LVH proved to be an independent prognosticator of CAD in contrast to arterial stiffness that was not related to CAD after accounting for established confounders. Therefore, LVM can reliably help physicians to identify high-risk hypertensives in whom an intensified therapeutic management is warranted.

Effects of oral paricalcitol therapy on arterial stiffness and osteopontin in hypertensive patients with chronic kidney disease and secondary hyperparathyroidism.

BACKGROUND: Arterial stiffness is linked to the progression of atherosclerosis, while activation of vitamin D receptor exerts favorable cardiovascular effects in patients with renal insufficiency. In this study, we investigated the effects of oral treatment with paricalcitol, a potent vitamin D receptor activator, on arterial stiffness and osteopontin, a marker of atherosclerosis, in hypertensive patients with chronic kidney disease (CKD) and secondary hyperparathyroidism. METHODS: We followed up 29 treated hypertensive patients (mean age: 74.1 years, 19 men, office blood pressure = 132/85 mmHg) with CKD stages 3-5 (mean glomerular filtration rate [GFR] = 19.4 ml/min/1.73 m2) who were on therapy with oral paricalcitol for 1 year. The control group consisted of 10 age-, sex-, and GFR-matched hypertensive patients with secondary hyperparathyroidism. RESULTS: After 1 year of treatment with paricalcitol compared to baseline, there was no statistical difference in levels of GFR, office blood pressure, and osteopontin (p = NS for all), while carotid-femoral PWV was reduced from 11.8 ± 2.6 m/s to 11.2 ± 2.4 m/s (p < 0.05). The control group exhibited no significant changes in carotid-femoral PWV (p = NS). CONCLUSIONS: Treatment with oral paricalcitol in hypertensive subjects suffering from CKD stages 3-5 and secondary hyperparathyroidism is accompanied by amelioration of arterial stiffness as reflected by the reduction of carotid-femoral PWV.

GLP-1 receptor agonists and cardiovascular outcome trials: An update.

Major cardiovascular (CV) outcome trials with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are currently available. These agonists have proven their CV safety, in harmony with the US Food and Drug Administration (FDA) recommendation for antidiabetic drugs. The potential cardioprotective effect of incretin-based therapies is attributed to their multiple non-glycaemic actions in the CV system, including changes in insulin resistance, weight loss, reduction in blood pressure, improved lipid profile and direct effects on the heart and vascular endothelium. Liraglutide, semaglutide and albiglutide have been demonstrated to reduce the risk of major adverse cardiac events (MACE), whereas lixisenatide and extended-release exenatide had a neutral effect. Thus, it is conceivable that there are different drug-specific properties across the class of GLP-1 RAs. In this review, we discuss the results of the five recently published randomised CV outcome trials with GLP-1 RAs, along with the potential differences and the pleiotropic actions of these agents on the CV system.

Renal resistive index in hypertensive patients.

Spectral Doppler ultrasonography provides the evaluation of renal resistive index (RRI), a noninvasive and reproducible measure to investigate arterial compliance and/or resistance. RRI seems to possess an important role in the evaluation of diverse cases of secondary hypertension. In essential hypertension, RRI is associated with subclinical markers of target organ damage and reflects renal disease progression beyond albuminuria and creatinine clearance. Also, RRI can estimate cardiovascular and renal risk. The evaluation of RRI may also help the therapeutic decisions. Given its simple assessment, RRI emerges as a simple method and a "multifunctional" tool that could help on the cardiovascular risk evaluation of the hypertensive patient.

Cardiovascular morbidity of severe resistant hypertension among treated uncontrolled hypertensives: a 4-year follow-up study.

Data regarding the prognosis of resistant hypertension (RHTN) with respect to its severity is limited. We investigated the cardiovascular risk of severe RHTN in a prospective observational study. A cohort of 1700 hypertensive patient with treated uncontrolled HTN was followed for a mean period of 3.6 ± 1.8 years. At baseline, standard clinical and laboratory workup was performed, including testing for secondary causes of RHT where applicable. Three groups were identified depending on presence of RHTN (office-based uncontrolled HTN under at least three drugs including a diuretic) and levels of office systolic blood pressure (BP): 1187 patients (70%) without RHTN, 313 (18%) with not-severe RHTN (systolic BP < 160 mmHg) and 200 (12%) with severe RHTN (systolic BP ≥ 160 mmHg). Endpoint of interest was cardiovascular morbidity set as the composite of coronary heart disease and stroke. During follow-up, incidence rates of cardiovascular events per 1000 person-years were 7.1 cases in the non-RHTN group, 12.4 cases in the not-severe RHTN group and 18 cases in the severe RHTN group. Unadjusted analysis showed that compared to uncontrolled patients without RHTN, patients with not-severe RHTN exhibited a similar risk but patients with severe RHTN had a significantly higher risk, by 2.5 times (CI: 1.28-4.73, p = 0.007). Even after multivariate adjustment for established risk factors including BP levels and isolated systolic HTN, severe RHTN remained as an independent predictor of the cardiovascular outcome (OR: 2.30, CI: 1.00-5.29, p = 0.05). In conclusion, among treated yet uncontrolled hypertensive patients, severe RHTN exhibits a significantly higher cardiovascular risk indicating the need for prompt management.

Uric acid as an independent predictor of coronary artery disease in essential hypertension: Data from an 8-year-follow-up study.

The role of serum uric acid (SUA) in cardiovascular risk prediction remains to be further determined. We assessed the predictive value of SUA for the incidence of coronary artery disease (CAD) in 2287 essential hypertensive patients who were followed up for a mean period of 8 years. The distribution of SUA levels at baseline was split by the median (5.2 mg/dL) and subjects were classified into those with high and low values. Hypertensives who developed CAD (n = 57) compared to those without CAD at follow-up (n = 2230) had at baseline higher SUA. In multivariate Cox regression model, among established confounders, high SUA (hazard ratio = 1.216, P = .016) turned out to be independent predictor of CAD. In essential hypertensive patients SUA independently predicts CAD.

Noninvasive assessment of haemodynamics in resistant hypertension: the role of the renal resistive index.

OBJECTIVE: The association of resistant hypertension (RHTN) with renal haemodynamics is unclear. Our aim was to evaluate differences in haemodynamic characteristics of patients with RHTN compared with patients with controlled hypertension (HTN) at the level of the heart, kidney and aorta. METHODS: We studied 50 patients with RHTN confirmed by ambulatory blood pressure monitoring and 50 controlled hypertensive patients matched for age and sex. All participants underwent renal Doppler ultrasound to determine the renal resistive index (RRI), a complete echocardiographic study including measurements of diastolic function and evaluation of augmentation index. RESULTS: Hypertensive patients with RHTN compared with those without RHTN had a significantly decreased E/A ratio (by 0.12, P = 0.043), an increased E/e' ratio (by 3.1, P < 0.001), increased albumin-to-creatinine ratio levels (by 49 mg/g, P = 0.023) and a significantly higher RRI (by 0.078, P < 0.001) but similar augmentation index values (P = 0.79). Logistic regression revealed that presence of RHTN was the strongest predictor of an RRI more than 0.7 after controlling for other haemodynamic variables including blood pressure levels. Receiver-operator characteristic analysis revealed an area under the curve for prediction of RHTN by the RRI alone of 80.3% (95% confidence interval: 0.72-0.89, P < 0.001). An RRI cut-point of 0.648 has a sensitivity of 78% and a specificity of 72% for prediction of RHTN. CONCLUSION: In a well treated hypertensive population, patients with RHTN show more pronounced renal and cardiac haemodynamic dysfunction compared with patients with controlled HTN. A greater RRI seems to be associated with RHTN and may help identify such patients.

Metabolic syndrome, independent of its components, affects adversely cardiovascular morbidity in essential hypertensives.

BACKGROUND: The metabolic syndrome (MS) is widespread among hypertensive patients. However, the net impact of MS on major atherosclerotic events beyond the cardiovascular risk imposed by its individual components remains controversial in this group. We sought to assess both the independent and incremental prognostic role of MS for unfavorable cardiovascular events in a cohort of essential hypertensives. METHODS: We followed up 2176 essential hypertensives free of cardiovascular disease for a median period of 40 months. All subjects had at least one annual visit. MS was defined according to the updated NCEP III criteria. Endpoint of interest was the incidence of stroke, coronary artery disease (CAD) and their composite. RESULTS: MS was present at baseline in 819 hypertensives (37.6%). MS group presented increased prevalence of resistant hypertension in comparison to MS free group (18.4% versus 10.6%, p < 0.001). The incidence of the composite end-point was 3.1% (69 events) across the follow-up period. Patients with MS were more likely to experience major adverse cardiovascular events (MACE) in comparison to reference category (3.7% versus 1.9%, log rank p = 0.024). While MS was an independent predictor for MACE, none of the individual components of the syndrome was associated independently with the endpoint. MS provided incremental discriminative value (Harrell's c, p < 0.05 for all) over individual risk factors for the incidence of MACE. CONCLUSIONS: MS predicts adverse cardiovascular events in hypertensives incrementally of its individual components. Early identification of MS in this population may enable more accurate prediction of future cardiovascular risk and could implement more efficient strategies in terms of primary prevention.

Nighttime vs. daytime blood pressure as a predictor of changes in left ventricular mass in hypertensive subjects.

Left ventricular hypertrophy (LVH) conveys an increased risk of cardiovascular morbidity and mortality. We aimed to compare the prognostic value of daytime and nighttime blood pressure (BP) on the changes in LVH status in newly diagnosed hypertensive subjects. Three hundred and five hypertensive, nondiabetic subjects (mean age 51.1 ± 10.2 years, 190 men) were prospectively studied for a mean period of 42 ± 17 months. At baseline and last follow-up visit, all patients underwent office and ambulatory BP monitoring, as well as echocardiographic assessment. We defined the following: LVH development/LVH persistence as the new-onset LVH at the end of follow-up or the presence of LVH at both baseline and the end of follow-up; left ventricular mass index (LVMI) reduction as a decline in LVMI at the end of follow-up of ≥ 15% compared with the baseline value. Multivariate Cox regression analyses revealed that baseline nighttime systolic BP was a significant predictor of LVH development/LVH persistence during follow-up (hazard ratio=1.066, P=0.02), whereas baseline daytime systolic BP was not. Moreover, the reduction of nighttime systolic BP is related to an almost threefold increase in the probability of LVMI reduction, independently of daytime BP reduction. In conclusion, nighttime BP constitutes a better prognosticator of left ventricular mass alterations over time in treated essential hypertensive patients than does daytime BP.

Left ventricular mass index as a predictor of new-onset microalbuminuria in hypertensive subjects: a prospective study.

BACKGROUND: We aimed to investigate the predictive role of left ventricular mass and its reduction on the development of new-onset microalbuminuria (MA) in newly diagnosed hypertensive patients. METHODS: A total of 207 nondiabetic, normoalbuminuric patients without clinical organ damage (aged 50.8 ± 10.1 years, 132 male, 84 smokers) with baseline office blood pressure (BP) 148/96 mm Hg were followed for a mean period of 3.3 ± 1.3 years. At baseline and last follow-up visit, all patients underwent office and 24-h ambulatory BP monitoring, albumin to creatinine ratio (ACR) determination, and echocardiographic assessment of left ventricular mass index (LVMI). All patients were treated with antihypertensive therapy during the follow-up period. We defined MA as ACR between 20 and 300 mg/g for men and 30-300 mg/g for women, effective BP control as office BP <140/90 mm Hg in ≥75% of total number of visits, and LVMI reduction as the decline of LVMI at end-follow-up of ≥15% with respect to the baseline value. RESULTS: Between baseline and last follow-up visit, LVMI decreased by 6.84 ± 21.5 g/m(2) (P < 0.01); 64.3% (n = 133) of participants achieved BP control during the follow-up period. Of the total population, 5.8% (n = 12) developed MA during follow-up. Cox-regression analysis, after adjustment for clinical variables, revealed that increase of LVMI by 1 s.d. (23.3 g/m(2)) conferred a 15% increased risk of new-onset MA, while LVMI reduction and BP control were both associated with almost 100% reduced risk of MA development. CONCLUSIONS: LVMI and its reduction were qualified as predictors of new-onset MA in newly diagnosed hypertensive patients, beyond BP control.

Ambulatory blood pressure monitoring in resistant hypertension.

ABPM constitutes a valuable tool in the diagnosis of RH. The identification of white coat RH and masked hypertension (which may fulfill or not the definition of RH) is of great importance in the clinical management of such patients. Moreover, the various ABPM components such as average BP values, circadian BP variability patterns, and ambulatory BP-derived indices, such as ambulatory arterial stiffness index (AASI), add significantly to the risk stratification of RH. Lastly, ABPM may indicate the need for implementation of specific therapeutic strategies, such as chronotherapy, that is, administration-time dependent therapy, and the evaluation of their efficacy.

Parallel deterioration of albuminuria, arterial stiffness and left ventricular mass in essential hypertension: integrating target organ damage.

BACKGROUND: Albuminuria, arterial stiffening and left ventricular hypertrophy (LVH) constitute target organ damage. We estimated whether increased urinary albumin excretion, assessed by albumin-to-creatine ratio (ACR), and carotid to femoral pulse wave velocity (c-f PWV) were accompanied by augmented left ventricular (LV) mass index (LVMI) in hypertension. METHODS: In 428 non-diabetic untreated hypertensives (257 men, mean age = 52 years, office blood pressure (BP) = 146/93 mm Hg) the distributions of ACR and c-f PWV were split by the median (8 mg/g and 7.8 m/s, respectively). RESULTS: Age, male sex, 24 h systolic BP, ACR and c-f PWV were the independent predictors of LVMI (R(2) = 0.478, p < 0.0001). Among patients with low ACR (n = 198), those with high c-f PWV (n = 84) compared to those with low c-f PWV (n = 114) were characterized by increased LVMI (by 8.9 g/m(2), p = 0.012) and prevalence of LVH (30 vs. 14%, p = 0.015). Similarly among patients with high ACR (n = 230), those with high c-f PWV (n = 123) compared to those with low c-f PWV (n = 107) exhibited heightened LVMI (by 13.6 g/m(2), p = 0.001). CONCLUSIONS: Increased ACR in conjunction with pronounced arterial stiffness is accompanied by augmented LV mass and higher LVH rates. Furthermore, the interrelationships between albuminuria, c-f PWV and LVMI suggest parallel target organ damage progression.

ADMA, C-reactive protein, and albuminuria in untreated essential hypertension: a cross-sectional study.

BACKGROUND: Asymmetric dimethylarginine (ADMA) and subclinical inflammation are associated with atherosclerosis progression, whereas microalbuminuria is an established index of hypertensive organ damage. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: In an outpatient hypertensive unit, 296 nondiabetic and untreated participants with hypertension were studied. Participants with atherosclerotic cardiovascular disease, severe valvulopathy, congestive heart failure, presence of neoplastic or other concurrent systemic disease, atrial fibrillation, serum creatinine level > 1.5 mg/dL in men and > 1.4 mg/dL in women, and urinary albumin excretion > 300 mg/24 h were excluded. PREDICTORS: ADMA and high-sensitivity C-reactive protein (hs-CRP) levels. OUTCOME VARIABLE: Albuminuria assessed using albumin-creatinine ratio (ACR). MEASUREMENTS: Participants underwent ambulatory blood pressure monitoring, echocardiography, routine assessment of metabolic profile, ADMA, and hs-CRP, whereas ACR was determined as the mean of 3 values in nonconsecutive morning spot urine samples. RESULTS: 64 participants had an ACR of 30-300 mg/g. Stratification based on ADMA level showed that participants with hypertension in quartile [Q] 4 compared with those in Q3, Q2, and Q1 showed the highest ACRs (53.2 vs 31.2 vs 30.4 vs 16.7 mg/g; P < 0.008 for all). Moreover, stratification based on hs-CRP level showed that participants with hypertension in Q4 (69.8% had microalbuminuria) showed the highest ACRs (72.2 vs 25.6, 16.2, and 19.2 mg/g for Q3, Q2, and Q1, respectively; P < 0.008 for all). Stepwise regression analysis showed that age, 24-hour systolic blood pressure, hs-CRP level, ADMA level, and the interaction of hs-CRP with ADMA were independent predictors of ACR (R(2) = 0.674; P < 0.001). LIMITATIONS: Cross-sectional study. CONCLUSIONS: In patients with untreated essential hypertension, increased hs-CRP and ADMA levels are associated with microalbuminuria, suggesting the involvement of inflammation and endothelial dysfunction in vascular and kidney damage.

Leontio Lyceum ALbuminuria (3L Study) epidemiological study: aims, design and preliminary findings.

INTRODUCTION: The significance of microalbuminuria (MA) in paediatric essential hypertension has yet to be established. The Leontio Lyceum ALbuminuria Study (3L Study) was designed to determine the prevalence of MA among Greek schoolchildren and to evaluate these rates in relation to the children's anthropometric and lifestyle characteristics, and dietary habits. METHODS: During April 2009, 498 students from the Leontio Lyceum, aged 12-17 years (7th-12th grade), were asked to participate in the 3L Study. For each child a questionnaire was completed that was developed for the purposes of the study to retrieve information on socio-demographic and lifestyle characteristics, as well as dietary habits (through a semi-quantitative Food Frequency Questionnaire), and physical activity status. Overweight and obesity were defined using the international body mass index cut-off points established for children and young people. Office blood pressure (BP) was measured on two different occasions and those students who had BP >95th percentile for gender, age and height on both occasions were considered as hypertensives. Microalbuminuria was determined as albumin to creatinine ratio >or=22 mg/g in boys and >or=31 mg/g in girls in a morning spot urine sample using a quantitative assay (DCA 2000). RESULTS: The prevalence of MA was found to be 12.9% and that of childhood hypertension 5.2%. The prevalence of overweight status was 25.8% and 5.8% of the students were classified as obese. Low physical activity was reported by 7% of boys and girls, while 46.5% of the students reported participation in vigorous physical activities during a normal week. Based on the KIDMED score of each student, only 6% of them were classified as high adherers to a Mediterranean diet and 41.9% were classified as having very low diet quality. CONCLUSIONS: In this paper we present the aims, design and preliminary results of an epidemiological study on MA, hypertension, increased body size and lifestyle characteristics among Greek schoolchildren.