Cardiovascular Events In Hypertension Research Articles

Evening anti-hypertensive dosing, blood pressure and cardiovascular events in hypertensive: Updated meta-analysis of 41 trials in 65,271 patients

Abstract Introduction In 2022, the International Society of Hypertension and World Hypertension League released a position paper noting that there is limited evidence on the impact of bedtime versus other time dosing of antihypertensives on 24-h BP profile and on cardiovascular morbidity and mortality. Since then, the Treatment In Morning versus Evening (TIME) trial results which enrolled over 20 thousand participants was published. This study aims to update our prior meta-analysis in 2020 (Sunjaya et al. EHJ. Vol. 41:S2) in light of this new results. Purpose In patients with hypertension does evening dosing of anti-hypertensive compared to morning dosing led to better reduction in pressure, blood pressure control and reduced cardiovascular morbidity. Methods A meta-analysis was performed based on randomized controlled trials obtained from Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline and Medline ahead of print published between 2000 and February 2023. Main outcome measures include mean 24 hour systolic and diastolic blood pressure, cardiovascular events as well as prevalence of blood pressure in control. Data synthesis and analysis was done using RevMan 5.3 using a random effects model. Results A total of 41 randomized controlled trials, representing 65,271 patients were included in this meta-analysis. Most studies evaluate the administration of mixed anti-hypertensive with ≥1 medication ingested at bedtime, calcium channel blockers (CCBs) or angiotensin receptor blockers (ARBs) with sample sizes ranging from 30 to 21,104 patients. Evening administration of anti-hypertensive was found to significantly lower 24-hour systolic blood pressure (Mean difference = -1.09, 95% CI -1.97 to -0.20, p = 0.02) and 24-hour diastolic blood pressure (Mean difference = -1.05, 95% CI -1.60 to -0.51, p = 0.0002). Significant reduction in cardiovascular events were found in the evening dosing group (RR = 0.53, 95% CI 0.38 to 0.73, p = 0.0001). Discussion: While evening administration was found to result in significantly lower systolic and diastolic blood pressure, both reductions were found to not be clinically meaningful (At least 5 mmHg for systolic and at least 3 mmHg as per 2022 Hypertension Academic Research Consortium consensus). Few studies have reported the impact on cardiovascular events (7 studies), mostly contributed by one research group (Hermida et al. 4 studies). Sensitivity analyses conducted removing studies conducted by this research group resulted in a non-significant pooled risk being found, though with result from only 3 studies. Conclusion For patients with hypertension, current evidence suggests no significant impact on blood pressure levels. While a reduction in the risk for cardiovascular events was found, this result was strongly contributed by that from one setting. Further studies remain required to answer this important question due to its possible widespread impact on clinical practice.Figure 1MACEFigure 2Systolic Blood Pressure

S-50-5: SALT SENSITIVITY AS MARKER FOR HYPERTENSION MANAGEMENT

Arterial hypertension is one of the most critical risk factors for cardiovascular (CV) disease, stroke, and chronic kidney disease (CKD). According to the current guidelines on hypertension management, the identification of one or more CV risk factors requires an earlier and more intensive treatment paradigm. Salt sensitivity (SSy), defined as susceptibility to changes in blood pressure related to dietary salt intake, is a well-known independent risk factor for CV disease in both the general and hypertensive population, even though it is not included in current guidelines. Is has been reported that SSy affects 30_50% of hypertensive and 25% of normotensive subjects. Salt sensitivity is more common in the elderly, women, African Americans, and patients with CKD and insulin resistance. The diagnosis of SSy is complex and not entirely standardized. The two main methods for SSy assessment are the dietary protocol versus the acute salt load. The dietary protocols typically evaluate the blood pressure variation between short periods of low and high sodium diet and often differ in both the duration and the amount of salt intake. Acute test (which consists of an i.v. infusion of 2 L of physiological solution over 2 hours) evaluates mean blood pressure (MBP) variation between the end and the start of the infusion. Three different blood pressure responses are possible: no substantial variation [salt resistant (SR) subjects], an increase in blood pressure [salt sensitive (SS) subjects], or a paradoxical decrease in blood pressure [reverse salt sensitive (RSS) subjects]. Although RSS subjects have been recognized as a third distinct group since the early 1990 s, many studies included them in the group of SR subjects. Recently, the concept of reverse salt sensitivity has been re-evaluated in relation to CV risk. Previous studies have shown an increased risk of developing cardiovascular events, hypertensive heart disease and microalbuminuria among SS patients. In our recent paper, the SS and RSS condition appear to be equivalent risk factors for CV events in hypertensives. Finally, a J curve relationship between dietary salt and cardiovascular damage has been proposed. Different pathophysiological mechanisms can be involved in SSy: renal autoregulation (Pressure natriuresis curve), Renin angiotensin aldosterone system, sympathetic nervous system activity, Insulin resistance, peripheral vascular resistances, sodium storage skin, genetic predisposition. Classification according to salt sensitivity can help in personalization of salt intake indication, intensity of therapy and timing of follow up.

Elevated body mass index increases the risk of cardiovascular events in hypertensive patients accompanied with obstructive sleep apnea: A cohort study

BackgroundEffects of body mass index (BMI) on cardiovascular events are inconsistent. We aimed to investigate the association of BMI with cardiovascular events in hypertensives with obstructive sleep apnea (OSA). MethodsHypertensives with OSA diagnosed with polysomnography between 2011 and 2013 in UROSAH cohort were followed up till Jan 2021. Outcomes were non-fatal cardiovascular events and cardiac death. Cox regression was used to estimate the relationship of continuous and categorical BMI with total and specific outcomes. Sensitivity analyses were performed by excluding those on OSA treatment or underweight patients. Stratified analyses were conducted by parameters including sex and age. Results2239 hypertensives with OSA were included with 405 normal weight (BMI<25 kg/m2), 1164 overweight (25–29.9 kg/m2) and 670 obesity (≥30 kg/m2). 206 non-fatal cardiovascular events and 18 cardiac death were recorded during 6.6 years follow-up. Compared with normal weight group, overweight (HR=1.53, 95%CI: 1.01–2.32, P = 0.047) and obesity groups (1.85, 1.19–2.86, P = 0.006) showed increased risk for cardiovascular events, significant in obesity group and marginal in overweight group in fully-adjusted model. In specific events, obesity showed significantly elevated HR for non-fatal cardiovascular events (1.64, 1.04–2.60, P = 0.035). Continuous BMI showed significantly increased HR for total and specific events in all models. Sensitivity analysis yielded consistent results. In stratification analysis, stronger association between obesity and cardiovascular events was observed in the young (HR=5.97, P interaction=0.030). ConclusionsBMI is in positive association with cardiovascular events in hypertensives with OSA, emphasizing importance of maintaining healthy BMI for prevention of adverse events in this population, on the basis of guideline-recommended treatment.

Prognostic value of home blood pressure monitoring in patients under antihypertensive treatment.

The prognostic value of home blood pressure monitoring (HBPM) has been investigated in several studies in the general population, demonstrating its independent association with cardiovascular events. However, in the case of treated hypertensive subjects, evidence is controversial. Our purpose was to evaluate the prognostic value of HBPM in this population. Medicated hypertensive patients who performed a 4-day HBPM (Omron® HEM-705CP-II) between 2008 and 2015 were followed up for a median of 5.9 years, registering the occurrence of a composite primary outcome of fatal and non-fatal cardiovascular events. Cox regression models were used to analyze the prognostic value of HBPM, considering 4-day measurements, discarding the first day, and analyzing morning, afternoon and evening periods separately. We included 1582 patients in the analysis (33.4% men, median age 70.8 years, on an average of 2.1 antihypertensive drugs). During follow-up, 273 events occurred. HBPM was significantly associated with cardiovascular events in all five scenarios in the unadjusted models. When adjusting for office BP and other cardiovascular risk factors, the association remained marginally significant for the 4-day period, discarding first-day measurements HBPM (HR 1.04 [95% CI 1–1.1] and 1.04 [95% CI 1–1.1], respectively) and statistically significant for all separate periods of measurement: HR 1.32 (95% CI 1.01–1.72); 1.33 (95% CI 1.02–1.72); and 1.30 (95% CI 1.01–1.67), for morning, afternoon and evening, respectively. When analyzing separately fatal and non-fatal events, statistical significance was held for the former only. In conclusion, HBPM is an independent predictor of cardiovascular events in hypertensives under treatment.

RELATIONSHIPS BETWEEN NAFLD BIOCHEMICAL SCORES AND LEFT VENTRICULAR GEOMETRIC PATTERN IN NAÏVE ESSENTIAL HYPERTENSIVE PATIENTS

Objective: The not alcoholic fatty liver disease (NAFLD) is associated with an increased cardiovascular mortality and morbidity. An hypothesis for this association could be the left ventricular (LV) geometric alteration sometime found in hypertension that is a known prognostic factor for cardiovascular events in hypertension. We searched for a relationship between biochemical scores of NAFLD and left ventricular (LV) hypertrophy (LVH) or LV geometric patterns changes in a large group of never treated essential hypertensive (EH) patients. Design and method: In 434 naïve (49 ± 14 years, 234 males) we evaluated BMI, waist circumference, liver steatosis at abdominal echography, the biochemical scores of liver steatosis: Liver Fat Score (LFS), Fatty Liver Index (FLI), Hepatic Steatosis Index (NAÏVE), and the fibrosis scores: NAFLD Fibrosis Score (NFS), APRI, FIB-4, parameters of glucose and insulin homeostasis, liver blood tests, lipids, platelets count, glomerular filtration rate (GFR), reactive C protein. LV mass and relative wall thickness was calculated with echocardiography. Patients were classified in 4 groups of LV geometry: 1 = LV normal geometry, 2 = LV concentric remodeling, 3 = concentric LVH, 4 = eccentric LVH. Results: A LVH was present in 17.3% of patients, and these patients had higher LFS (P &lt; 0.001), FLI (P = 0.008), NAÏVE (P = 0.004) and NFS (P = 0.011) scores than patients without LVH. LVH was independently associated with the FLI score but not with fibrosis scores. The steatosis scores (LFS, NAÏVE, FLI) linearly increased across the four LV geometric patterns (P = 0.007, P = 0.001, P = 0.003, respectively). The fibrosis score NFS was significantly higher in subjects with concentric LVH (P = 0.041). The LFS was independently associated with BMI, GAUC, G120, and triglycerides levels. The NFS was independently associated with waist circumference, GFR and weakly with fasting glucose level. Ultrasound steatosis was not different among the four LV geometric patterns. Conclusions: In naïve EH patients the biochemical steatosis scores show a relationship with LVH and LV geometric changes, while fibrosis is associated with concentric LVH. An accurate investigation to reveal a NAFLD should be done in EH patients with altered LV geometry and to better understanding of mechanisms linking the two conditions.

Carotid vascular strain predicts cardiovascular events in patients with hypertension.

We aim to investigate prognostic effects of carotid strain (CS) and strain rate (CSR) in hypertension. We prospectively recruited 120 patients being treated for hypertension (65.8 ± 11.8 years, 58% male) in this observational study. Peak circumferential CS and peak CSR after ejection were identified using two-dimensional speckle tracking ultrasound. Major cardiovascular events were any admission for stroke, acute coronary syndrome, and heart failure. After a mean follow-up period of 63.6 ± 14.5 months, 14 (12%) patients had cardiovascular events. Age (75.3 ± 9.2vs 64.6 ± 11.6 years; p=0.001), systolic blood pressure (131.8 ± 15.5vs 143.1 ± 16.6mm Hg; p=0.021), diastolic blood pressure (74.6 ±11.4vs 82.1 ± 12.2mm Hg; p=0.039), use of diuretics (71vs 92%; p=0.014), carotid CS (2.17 ± 1.02vs 3.28 ± 1.14 %; p=0.001), and CSR (.28 ± .17vs .51 ± .18 1/s; p<0.001) were significantly different between the patients who did and did not reach the end-points. Multivariate Cox regression analysis controlling for age, systolic blood pressure, diastolic blood pressure, and use of diuretics showed that CS (HR .425, 95%CI .223-.811, p=0.009) and CSR (HR .001, 95%CI .000-.072, p=0.001) were independent predictors for cardiovascular events. In conclusions, decreased CS and CSR were associated with cardiovascular events in hypertension.

New-Onset Diabetes, Endothelial Dysfunction, and Cardiovascular Outcomes in Hypertensive Patients: An Illness-Event Model Analysis.

Background. Insulin resistance and endothelial dysfunction are common findings in hypertensives, both predisposing to a higher risk of diabetes and cardiovascular events. We designed this study to evaluate the role of endothelial dysfunction in three pathogenetic pathways: (1) from baseline to cardiovascular events, (2) from baseline to diabetes, and (3) from new-onset diabetes to cardiovascular events. Methods. We enrolled 653 Caucasian never-treated hypertensives. Endothelial dysfunction was investigated by strain-gauge plethysmography; incident diabetes and cardiovascular events were evaluated by an illness-event model analysis. Results. During the follow-up (median 113 months), we documented 191 new cardiovascular events and 92 new cases of diabetes. In a multiple Cox regression analysis, acetylcholine-stimulated forearm blood flow [100% decrease, hazard ratio: 2.42 (95% confidence interval = 1.72–3.40)] and serum high-sensitivity C-reactive protein [hazard ratio: 1.30 (95% confidence interval = 1.21–1.40)] had an independent association with cardiovascular outcomes. The incidence rate of cardiovascular outcomes in diabetes-developer patients was higher than in the diabetes-free ones (34.9 vs. 2.5 events per 100 persons-year). In an illness-event model, a 100% decrease in forearm blood flow was associated with a 55.5% hazard ratio increase (hazard ratio: 1.56, 95% confidence interval: 1.33–1.82) of transition 1 (from baseline status to cardiovascular events) and to an almost doubled increase (hazard ratio: 2.54, 95% CI: 2.00–3.25) of the risk of transition 2 (from baseline status to diabetes). No such effects were found in transition 3 (from diabetes to cardiovascular events). Conclusions. Endothelial dysfunction plays a primary role in the pathways leading to diabetes and cardiovascular events in hypertensives. When diabetes is overt, endothelial dysfunction has no predictive value for subsequent cardiovascular events.

COPD significantly increases cerebral and cardiovascular events in hypertensives

Essential hypertension and chronic obstructive pulmonary disease often coexist in the same patient. The aim of this study was to evaluate whether the addition of chronic obstructive pulmonary disease modifies the risk of cardiovascular events in hypertensives. We enrolled 1728 hypertensives. Study outcomes included fatal and non-fatal cardiovascular stroke and myocardial infarction, and cardiovascular death. During a mean follow-up of 57 months there were 205 major adverse cardiovascular events (2.47 per 100 pts/yr): cardiac (n117; 1.41 per 100 pts/yr) and cerebrovascular (n = 77; 0.93 per 100 pts/yr). In hypertensives with chronic obstructive pulmonary disease we observed a greater number of cardiovascular events than in hypertensives without respiratory disease (133 [5.55 per 100 pts/yr) vs 72 [1.22 per 100 pts/yr], respectively. The addition of chronic obstructive pulmonary disease to hypertension increased the incidence of total and non-fatal stroke of more than nine- (2.42 vs 0.32 per 100 pts/yr) and 11-fold (2.09 vs 0.22 per 100 pts/yr), respectively. The same trend was observed for total (2.88 vs 0.81 per 100 pts/yr) and non-fatal (2.67 vs 0.79 per 100 pts/y) myocardial infarction. The presence of chronic obstructive pulmonary disease in hypertensives significantly increases the risk of stroke, myocardial infarction and major adverse cardiovascular events.

Prognostic Value of Serum Uric Acid Levels to the Cardiovascular Events in Hypertensives

Uric acid is a product of the activity of xanthine oxidase, an enzyme increasingly implicated as a mechanistic participant in oxidant stress and cardiovascular disease. Contributing factors responsible for hyperuricemia are alcoholic and high-purine foods consumption, low water consumption and poorly exercising. In adults with essential hypertension an association with hyperuricemia is very common. Prevalence of hyperuricemia is 30% in untreated hypertensives and >75% in malignant hypertension. Uric acid is thought to play a pathogenic role in hypertension [1-3] mediated by several mechanisms such as inflammation, vascular smooth muscle cell proliferation in renal microcirculation, endothelial dysfunction, and activation of the renin – angiotensin – aldosterone system [4-7].

Evening anti-hypertensive dosing improves blood pressure control and reduce cardiovascular events in hypertensive: a meta-analysis of 40 trials in 44,167 patients

Abstract Introduction Nocturnal blood pressure (BP) and early morning BP surge have consistently been found to be a better prognostic marker of cardiovascular outcome than daytime BP. Most anti-hypertensive show greater blood pressure-lowering effect in the first 12 hours compared to the next 12 hours. Several prospective studies have shown better BP regulation and improved cardiovascular risk when anti-hypertensive are ingested at bedtime versus at awakening. Purpose In patients with hypertension does evening dosing of anti-hypertensive compared to morning dosing led to better reduction in pressure, blood pressure control and reduced cardiovascular morbidity. Methods A meta-analysis was performed based on randomized controlled trials obtained from Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline and Medline ahead of print published between 2000 and 2020. Main outcome measures include mean 24 hour systolic and diastolic blood pressure, cardiovascular events as well as prevalence of blood pressure in control. Data synthesis and analysis was done using RevMan 5.3 using a random effects model. Results A total of 40 randomized controlled trials, representing 44,167 patients were included in this meta-analysis. Most studies evaluate the administration of mixed anti-hypertensive with ≥1 medication ingested at bedtime, calcium channel blockers (CCBs) or angiotensin receptor blockers (ARBs) with sample sizes ranging from 30 to 19,084 patients. Evening administration of anti-hypertensive was found to significantly lower 24-hour systolic blood pressure (Mean difference = −1.05, 95% CI: −2.01 to −0.10, p=0.03) and 24-hour diastolic blood pressure (Mean difference = −1.09, 95% CI: −1.68 to −0.50, p=0.0003). Prevalence of controlled blood pressure was found to significantly increase with evening dosing (RR=1.15, 95% CI: 1.03 to 1.28, p=0.01). Significant reduction in cardiovascular events were found in the evening dosing group (RR=0.48, 95% CI: 0.03 to 0.68, p=&amp;lt;0.00001). Discussion Reduction in night-time blood pressure especially among non-dippers as reported in previous studies and higher prevalence of controlled blood pressure may explain the greater than 50% reduction in cardiovascular events in the evening dosing group. This marked benefit from a simple and inexpensive strategy certainly has great potential to benefit patients in practice. Even so, few studies have reported the prevalence of blood pressure in control (9 studies) and cardiovascular events (6 studies). Few has also studied this in geriatric populations where night-time hypotension and hypoperfusion may bring the most impact. Conclusion For patients with hypertension, evening dosing significantly improves blood pressure control and reduces the risk for cardiovascular events. Careful selection of anti-hypertensive administration time in patients is recommended given the possible benefits. Anti Hypertensive Dosing Forest Plot Funding Acknowledgement Type of funding source: None

Conventional and new electrocardiographic criteria for hypertension-mediated cardiac organ damage: A narrative review.

Hypertension-mediated organ damage (HMOD) is frequently observed in hypertensive patients at different cardiovascular (CV) risk profile. This may have both diagnostic and therapeutic implications for the choice of the most appropriate therapies. Among different markers of HMOD, the most frequent functional and structural adaptations can be observed at cardiac level, including left ventricular hypertrophy (LVH), diastolic dysfunction, aortic root dilatation, and left atrial enlargement. In particular, LVH was shown to be a strong and independent risk factor for major CV events, namely myocardial infarction, stroke, congestive heart failure, CV death. Thus, early identification of LVH is a key element for preventing CV events in hypertension. Although echocardiographic assessment of LVH represents the gold standard technique, this is not cost-effective and cannot be adopted in routine clinical practice of hypertension. On the other hand, electrocardiographic (ECG) assessment of HMOD relative to the heart is a simple, reproducible, widely available and cost-effective method to assess the presence of LVH, and could be preferred in large scale screening tests. Several new indicators have been proposed and tested in observational studies and clinical trials of hypertension, in order to improve the relatively low sensitivity of the conventional ECG criteria for LVH, despite high specificity. This article reviews the differences in the use of the main conventional and the new 12 lead ECG criteria of LVH for early assessment of asymptomatic, subclinical cardiac HMOD in a setting of clinical practice of hypertension.

Neutrophil to Lymphocyte Ratio as a Predictor of Left Ventricular Hypertrophy in Patients with Newly Diagnosed Hypertension

Concentric or eccentric left ventricular hypertrophy (LVH) is an independent prognostic factor of major cardiovascular events in hypertension (HT). A high neutrophil to lymphocyte ratio (NLR) is correlated with high mortality and poor prognosis in cardiovascular disease. This study was performed to investigate the associations between NLR and different left ventricular (LV) geometric patterns in patients with newly diagnosed HT.

Short-term blood pressure variability outweighs average 24-h blood pressure in the prediction of cardiovascular events in hypertension of the young.

The association of short-term blood pressure (BP) variability (BPV) with cardiovascular events (CVEs) is controversial. Aim of this study was to investigate whether BPV measured as weighted 24-h SD was associated with CVE in a prospective cohort study of young patients screened for stage 1 hypertension. We performed 24-h ambulatory BP monitoring in 1206 participants aged 33.1 ± 8.5 years, untreated at baseline examination. Participants were divided into two categories with low (<12.8 mmHg) or high (≥12.8 mmHg) SBPV. Hazard ratios for CVE associated with BPV expressed either as continuous or categorical variable were computed from multivariable Cox models. During 15.4 ± 7.4 years of follow-up there were 69 fatal and nonfatal CVE. In multivariable Cox models, high SBPV was an independent predictors of CVE [2.75 (1.65-4.58); P = 0.0001] and of coronary events [3.84 (2.01-7.35), P < 0.0001]. Inclusion in the model of development of hypertension requiring treatment during the follow-up, did not reduce the strength of the associations. Addition of SBPV to fully adjusted models had significant impact on risk reclassification and integrated discrimination (relative integrated discrimination improvement for BPV as continuous variable: 13.5%, P = 0.045, and for BPV as categorical variable: 26.6%, P = 0.001). When the coefficient of variation was used as BPV metric similar results were obtained. Of note, in all Cox models average 24-h BP was no longer an independent predictor of outcome after BPV was included. Short-term BPV adds to the risk stratification for cardiovascular events in young-to-middle-age patients screened for stage 1 hypertension over and above traditional 24-h ambulatory monitoring indexes.

A Novel Just-in-Time Contextual Mobile App Intervention to Reduce Sodium Intake in Hypertension: Protocol and Rationale for a Randomized Controlled Trial (LowSalt4Life Trial).

BackgroundHigh sodium intake is a significant public health problem in the United States. Interventions that lower sodium intake can decrease blood pressure and improve cardiovascular outcomes. Restaurants and grocery stores are prime targets for intervention with about 77% of all sodium intake in the average US diet coming from processed and restaurant foods.ObjectiveThis study proposes that a mobile app intervention that promotes low-sodium alternatives at grocery stores and restaurants will reduce dietary intake of sodium and improve confidence following a low-sodium diet in hypertension.MethodsIn this single-center, prospective, open-label study, patients will be randomized to a mobile app or usual care for 8 weeks. We will randomize 50 patients (age>18 years) diagnosed with hypertension and on antihypertensive therapy for at least 3 months in a 1:1 manner stratified by gender. Study subjects will receive the mobile app, LowSalt4Life, or usual dietary advice for 8 weeks. LowSalt4Life provides a multifaceted intervention based on just-in-time contextual tailored messages at grocery stores and restaurants. The primary endpoint is the change in the estimated 24-hour urinary excretion of sodium from spot urine. Secondary outcomes include change in the sodium content of the food frequency questionnaire, confidence in following a low-sodium diet, urine chloride and creatinine dipsticks, and blood pressure.ResultsThe project was funded in May 2016 until April 2018. This trial is currently enrolling patients. To date, 26 of the 50 patients needed have been enrolled. Results will be available in the Spring of 2019.ConclusionsThis randomized controlled trial will test the efficacy of just-in-time contextual tailored messages through a novel mobile app 8-week intervention on urinary sodium excretion in patients with hypertension. We will address a critical evidence gap in the care of patients with hypertension. If effective, this intervention could be scaled to assess effects on blood pressure and cardiovascular events in hypertension.Trial RegistrationClinicalTrials.gov NCT03099343; https://clinicaltrials.gov/ct2/show/NCT03099343 (Archived by WebCite at http://www.webcitation.org/735HNzKlQ)International Registered Report Identifier (IRRID)PRR1-10.2196/11282

Effects on 24-hour blood pressure variability of ace-inhibition and calcium channel blockade as monotherapy or in combination

Cardiovascular events in hypertensives are associated with elevated average blood pressure (BP) and higher short-term BP variability (V), but little is known on treatment effects on BPV and on how to assess changes in short-term BPV. Aim of our study was to address the methodology of short-term BPV assessment and its reduction by Lercanidipine (L) or Enalapril (E) and their combination, through analysis of 24-hour ambulatory BP recordings from two studies including subjects of different age. Study-1: 64 middle-age hypertensives (52.9 ± 9.5 yrs) received L and E s.i.d. at 10 mg (L10, E10) or 20 mg doses (L20, E20) for 8 weeks. Study-2: 66 elderly hypertensives (65.5 ± 4.7 yrs) received placebo, L10, E20 and L10 + E20 s.i.d. for 4 weeks. In middle-age subjects, both L and E decreased mean BP and, at the highest dose, also short-term BPV. In elderly subjects, L10 alone or in combination with E20 reduced BPV. Treatment-induced reductions in BP levels and BPV were uncorrelated. Different methods for short-term BPV assessment did not always provide superimposable results in the elderly. Our study supports a better reduction of BPV by L in the elderly and by E + L combination at any age, suggesting BPV reduction to be independent from reduction in average BP.

PP.06.10] BLOOD PRESSURE VARIABILITY AND TARGET ORGAN DAMAGE IN HYPERTENSION

Objective: Hypertension is associated with several markers of subclinical target organ damage (TOD). Short-term blood pressure variability (SBPV) is a prognostic factor for cardiovascular events in hypertensives. We hypothesized that there is a relationship between SBPV and TOD in never-treated hypertensives. Design and method: We enrolled 943 consecutive essential hypertensives (mean age 53 ± 12 years, 497 males). Markers of subclinical TOD [left ventricular mass index (LVMI), pulse wave velocity (PWV), total arterial compliance (TAC), ankle-brachial index (ABI) and estimated glomerular filtration rate (eGFR)] and 24-h ambulatory blood pressure were evaluated in all patients. LVMI was assessed echocardiographically using the Devereux formula. Carotid-femoral PWV was estimated with the Complior. eGFR was calculated by the Cockcroft-Gault formula. ABI was calculated by dividing the highest ankle systolic blood pressure by the highest brachial systolic blood pressure. The ratio of stroke volume to pulse pressure was measured echocardiographically as a surrogate of TAC. SBPV was calculated as follows: 1) SD of 24-hour, daytime, or nighttime SBP and 2) weighted SD of 24-hour SBP. Results: In multivariable regression analysis, all four variables of SBPV exhibited significant association with LVMI (p = 0.014, p = 0.002, p = 0.002 and p < 0.001, respectively), PWV (p = 0.021, p = 0.015, p = 0.055 and p = 0.006, respectively) and TAC (p = 0.048, p = 0.020, p = 0.036 and p = 0.006, respectively). In multivariable analysis, ABI and eGFR were not associated with indices of SBPV. We assessed TOD based on 2013 European Guidelines for Hypertension [left ventricular hypertrophy (LVMI>115 g/m2 in men and >95 g/m2 in women), increased PWV (PWV>10m/s), decreased ABI (ABI<0.9) and decreased renal function (eGFR<60 ml/min)]. In multivariable logistic regression analysis, SBPV indices were not associated with markers of TOD (P > 0.05). Conclusions: Our findings support a complex relationship between SBPV and TOD in hypertension. Specifically, SBPV is more closely related to markers of ventricular and vascular compliance than other markers of TOD in hypertension.

High Serum Immunoglobulin G and M Levels Predict Freedom From Adverse Cardiovascular Events in Hypertension: A Nested Case-Control Substudy of the Anglo-Scandinavian Cardiac Outcomes Trial

AimsWe aimed to determine whether the levels of total serum IgM and IgG, together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), can improve cardiovascular risk discrimination. Methods and ResultsThe Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized 9098 patients in the UK and Ireland into the Blood Pressure-Lowering Arm. 485 patients that had cardiovascular (CV) events over 5.5years were age and sex matched with 1367 controls. Higher baseline total serum IgG, and to a lesser extent IgM, were associated with decreased risk of CV events (IgG odds ratio (OR) per one standard deviation (SD) 0.80 [95% confidence interval, CI 0.72,0.89], p<0.0001; IgM 0.83[0.75,0.93], p=0.001), and particularly events due to coronary heart disease (CHD) (IgG OR 0.66 (0.57,0.76); p<0.0001, IgM OR 0.81 (0.71,0.93); p=0.002). The association persisted after adjustment for a basic model with variables in the Framingham Risk Score (FRS) as well as following inclusion of C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NtProBNP). IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively. The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG, and there was improvement in continuous and categorical net reclassification (17.6% and 7.5% respectively) as well as in the integrated discrimination index. ConclusionHigh total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events, particularly those attributed to CHD, in patients with hypertension.

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

BackgroundThe 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. MethodsWe 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. ResultsMS 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. ConclusionsMS 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.

Metabolic syndrome is associated with left ventricular dilatation in primary hypertension.

Metabolic syndrome (MS) has been shown to predict cardiovascular events in hypertension. Recently, a new four-group left ventricular (LV) hypertrophy classification based on both LV dilatation and concentricity was proposed. This classification has been shown to provide a more accurate prediction of cardiovascular events, suggesting that the presence of LV dilatation may add prognostic information. We investigated the relationship between MS and the new classification of LV geometry in patients with primary hypertension. A total of 372 untreated hypertensive patients were studied. Four different patterns of LV hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The overall prevalence of MS and LV hypertrophy (LVH) was 29% and 61%, respectively. Patients with MS showed a higher prevalence of LVH (P=0.0281) and dilated LV geometries, namely eccentric dilated and concentric dilated hypertrophy (P=0.0075). Moreover, patients with MS showed higher LV end-diastolic volume (P=0.0005) and prevalence of increased LV end-diastolic volume (P=0.0068). The prevalence of LV chamber dilatation increased progressively with the number of components of MS (P=0.0191). Logistic regression analysis showed that the presence of MS entails a three times higher risk of having LV chamber dilatation even after adjusting for several potential confounding factors. MS is associated with LV dilatation in hypertension. These findings may, in part, explain the unfavourable prognosis observed in patients with MS.

Central aortic pressure indices and their correlation with brachial pressure in hypertensive subjects on newer angiotensin receptor blockers olmesartan and telmisartan

Background: Efficacy of Fixed-dose combination of olmesartan and amlodipine on central aortic pressure and Aortic pulse wave velocity (PWV), which are independent predictors of adverse cardiovascular events in hypertension is lacking. Aim of this study was to correlate the effects of fixed-dose combination therapy with olmesartan 20mg and amlodipine 5mg on central aortic blood pressure (CBP) indices in mild to moderate hypertensive subjects with controlled office BP. Methods: Twenty seven patients with brachial systolic BP 140 mmHg and/or diastolic BP 90 mmHg on three office readings who received fixed-dose combination therapy with olmesartan 20mg and amlodipine 5mg for atleast 12 weeks were included. CBP was measured with Periscope using standard cuff BP measurements and proprietary software utilizing a validated transfer function to convert the brachial waveform. Statistical analysis was done with SPSS version 10. Results: Average age of the study group was 47 years. Carotid femoral pulse wave velocity was 1210.2 454.5 cm/sec. Average brachial SBP, DBP and pulse pressure (PP) at the end of the study was 138.8 11.5, 75.9 9.6 and 62.1 12.8 mm of Hg. Average aortic SBP, DBP and pulse pressure (PP) at the end of the study was 121.5 13.8, 75.6 6.0 and 45.4 12.3 mm of Hg. Aortic augmentation pressure and aortic augmentation index noted were 13.7 9.1 mm of Hg and 28.1 10.7 respectively. A significant positive correlation was noted between brachial SBP and aortic SBP (r1⁄40.603, p < 0.001), brachial DBP and aortic DBP (r1⁄40.775, p < 0.001), brachial PP and aortic PP (r1⁄40.622, p<0.001). Conclusions: Combination therapy with fixed-dose olmesartan 20mg and amlodipine 5mg were shown to substantially benefit pulsatile hemodynamics (i.e. CBP and indices, AIx and PWV) and have beneficial effects on central aortic BP beyond brachial BP lowering with excellent correlation between the two BP parameters.