Long-term endothelial dysfunction after trans-radial catheterization: A meta-analytic approach.

BACKGROUND: Following cardiac catheterization using radial artery (RA) access, persistent endothelial dysfunction may limit the use of RA as a conduit during coronary artery bypass graft (CABG) surgery. We reviewed published literature to investigate the effects of transradial coronary catheterization on RA endothelial function. METHODS: We searched PubMed from inception to April 2017 for published studies assessing RA endothelial function late (≥1 month) after coronary catheterization. A total of 12 eligible published studies (n = 490 patients) were included in the final quantitative synthesis. Statistical heterogeneity among studies was assessed by the I2 . A random effects model was used to calculate the pooled estimate for standardized mean difference (SMD). Meta-regression analysis was used to explore predictors of change in RA endothelial function following catheterization. RESULTS: In all studies, a significant reduction in endothelium dependent response was observed post-catheterization (SMD = -0.53, 95% confidence interval [CI]: -0.93 to -0.13, P = 0.01) and a marginal, non-significant, reduction in endothelium independent response (SMD = -0.38, 95%CI: -0.77, 0.01, P < 0.059). In controlled studies, using the contralateral RA as a control, a significant impairment in endothelial function was confirmed (SMD = -6.26, 95%CI: -9.71 to -2.81, P < 0.0001), while the change in endothelium-independent response was not significant (SMD = -4.46, 95%CI: -13.3 to 4.37, P = 0.32). In meta-regression analysis male gender (z = 2.36, P = 0.018) and increasing time following catheterization (z = 2.62, P = 0.009) were associated with less RA endothelial dysfunction. CONCLUSIONS: Transradial catheterization impairs endothelium dependent vasodilatory properties of the cannulated RA, which do not recover even several months post-catheterization. Non-recovery of vasomotor function of cannulated RAs may limit their use as arterial grafts during CABG surgery.

Predictors of stent strut malapposition in calcified vessels using frequency-domain optical coherence tomography.

BACKGROUND AND AIMS: Malapposition of stent struts to the arterial wall and suboptimal stent expansion have been linked with poor outcomes following percutaneous coronary intervention (PCI). The purpose of this study was to use optical coherence tomography (OCT) to investigate stent strut malapposition in relation to calcium distribution. METHODS AND RESULTS: Twenty-three PCI patients underwent OCT before and after stent deployment. Patient and procedural details and lesion characteristics - including the extent and depth of calcification - were measured, and the number of malapposed struts following final postdilatation was quantified. Patient and lesion characteristics associated with malapposition were assessed using univariate and multivariate analyses. The mean lesion length was 25.2 ± 10.8 mm, with a minimal lumen area (MLA) of 2.2 ± 1.2 mm². Eight percent of all stent struts were malapposed, most commonly in the proximal part of the stent. By univariate analysis, the percentage of malapposed struts was found to correlate with the circumferential extent of calcification (P=.04); however, no correlation was seen with the depth of calcification. Using multivariate analysis, the circumferential extent of vessel wall calcification was the only plaque feature found to correlate with the percentage of malapposed struts (P=.01). CONCLUSIONS: Using OCT to assess vessel wall characteristics, the circumferential extent of superficial calcification seen, and not the depth, correlated well with the percentage of malapposed struts following PCI.

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.

Relation of impaired coronary microcirculation to increased urine albumin excretion in patients with systemic hypertension and no epicardial coronary arterial narrowing.

Coronary flow reserve (CFR) is impaired and urinary albumin excretion is increased in patients with essential hypertension. Our aim was to investigate the associations between CFR and cardiac and renal damage in hypertensives. For this purpose we studied 37 never-treated hypertensives (57.9 years old, 16 men) without chest pain but with a positive ischemia stress test result and normal coronary arteries on coronary angiogram. CFR was calculated by a 0.014-inch Doppler guidewire (Flowire, Volcano, San Diego) in the left anterior descending artery in response to bolus intracoronary administration of adenosine (60 µg) as the ratio of hyperemic to basal average peak velocity of the distal vessel. All participants underwent complete echocardiographic study including left ventricular diastolic function evaluation by tissue Doppler imaging (peak early diastolic velocity/peak atrial systolic velocity) and determination of the albumin-to-creatinine ratio (ACR). Hypertensives with low CFR (<2.5, n = 22) compared to those with high CFR (n = 15) exhibited a larger left ventricular mass index by 10.9 g/m(2) (p = 0.045) and ACR values by 10 mg/g (p <0.001). CFR was negatively correlated with logACR (r = -0.511, p = 0.001). LogACR (beta -0.792, p <0.001), male gender (beta 0.313, p = 0.005), left ventricular mass index (beta -0.329, p = 0.007), and peak early diastolic velocity/peak atrial systolic velocity (beta 0.443, p <0.001) were the only independent predictors of CFR in linear regression analysis (adjusted R(2) = 0.672). In conclusion, never-treated asymptomatic hypertensives who exhibit impaired CFR and angiographically normal epicardial arteries are characterized by intrarenal vascular damage as reflected by increased ACR. These findings suggest a plausible role of ACR estimation in the identification of hypertensive subjects with early coronary microvascular dysfunction.

Impaired exercise tolerance is associated with increased urine albumin excretion in the early stages of essential hypertension.

BACKGROUND: Our aim was to investigate the relationship between impaired exercise capacity and albumin excretion level in the setting of never treated essential hypertension. DESIGN AND METHODS: For this purpose, 338 consecutive essential hypertensives (52 ± 8.5 years, 227 males, office BP = 148.6/96.1 mmHg) performed a negative for myocardial ischemia, maximal treadmill exercise testing and were classified based on the gender specific median value of the amount of metabolic equivalents (METs) achieved (10.1 ml/kg/min for women and 11 ml/kg/min for men) as fit (n = 177) and unfit (n = 161). All the participants underwent 24-h ambulatory BP monitoring, complete echocardiographic study including left ventricular diastolic function evaluation and determination of albumin to creatinine ratio (ACR) on two non-consecutive morning spot urine samples. RESULTS: Unfit hypertensives compared to the fit ones were older by 4.5 years (p < 0.001) and had greater waist circumference by 4.5 cm (p < 0.001), body mass index by 1.3 kg/m(2) (p = 0.001), 24-h pulse pressure by 3.0 mmHg (p = 0.005), ACR levels by 12.6% (p = 0.003) and prevalence of microalbuminuria (19.5% vs 10.3%, p = 0.007) while the differences in diastolic function indices lost significance after adjustment for confounders. By applying stepwise multivariate linear regression analysis in order to identify the predictors of METs, it was revealed that age (ß = -0.338, p = 0.045), gender (ß = 0.274, p = 0.045), body mass index (ß = -0.230, p = 0.045) and logACR (ß = -0.151, p = 0.004) were the only independent predictors of exercise capacity. CONCLUSIONS: Increased ACR is associated with diminished exercise capacity in the early stages of essential hypertension independently from adverse cardiac adaptations, further elucidating the adverse prognostic role of albuminuria in this setting.

Similar levels of low-grade inflammation and arterial stiffness in masked and white-coat hypertension: comparisons with sustained hypertension and normotension.

OBJECTIVE: The clinical significance of masked hypertension (MHT) and white-coat hypertension (WCHT) remains controversial, whereas subclinical inflammation and arterial stiffness are associated with an adverse prognosis. We examined the interrelationships of MHT, WCHT, and sustained hypertension (SHT) with high-sensitivity C-reactive protein (hs-CRP) and arterial stiffness. METHODS: Our population consisted of 291 untreated nondiabetic patients with MHT [office blood pressure (BP) < 140/90 mmHg and daytime BP ≥ 135/85 mmHg; n = 32], WCHT (office BP ≥ 140/90 mmHg and daytime BP < 135/85 mmHg; n = 81), SHT (office BP ≥ 140/90 mmHg and daytime BP ≥ 135/85 mmHg; n = 178), and 44 age-matched and sex-matched control normotensives. RESULTS: SHT compared with WCHT, MHT, and normotension exhibited higher pulse wave velocity (PWV; 8.2 ± 1.4 vs. 7.5 ± 1.2 vs. 7.3 ± 0.9 vs. 6.8 ± 0.5 m/s, respectively; P < 0.05) and hs-CRP (2.8 ± 0.7 vs. 2.2 ± 0.6 vs. 1.9 ± 0.4 vs. 1.2 ± 0.3 mg/l, respectively; P < 0.05), independently of confounders. Of note, there was no difference between the MHT and WCHT groups with regard to hs-CRP and PWV levels (P = not significant). In hypertensives, hs-CRP was associated with 24-h systolic BP (r = 0.350, P < 0.0001) and PWV (r = 0.228, P < 0.0001), whereas PWV was associated with 24-h systolic BP (r = 0.330, P < 0.0001). CONCLUSION: MHT and WCHT represent two states of equivalent subclinical vascular dysfunction reflected by hs-CRP and PWV. Moreover, MHT and WCHT are characterized by a higher degree of inflammatory activation and arterial stiffening compared with normotension and by a lesser degree compared with SHT. The association of 24-h BP with both hs-CRP and PWV underscores the dominant role of hemodynamic load on hypertensive damage progression.

New-onset diabetes and cardiovascular events in essential hypertensives: a 6-year follow-up study.

BACKGROUND: Controversy still exists regarding the impact of new-onset diabetes (NOD) on CV outcomes among patients with hypertension. Our aim was to determine the incidence of NOD in essential hypertensives and to evaluate its association with major cardiovascular (CV) events. METHODS: We followed-up for a mean period of 6 years 1572 essential hypertensives (mean age 54.3 years, 696 males) for the incidence of NOD, as well as of fatal and non-fatal coronary artery disease and stroke. Based on the development of NOD, the cohort was divided into patients with pre-existing diabetes (10%), patients with NOD (10%) and those who remained free from diabetes. RESULTS: During the follow-up period, new or recurrent cases of coronary artery disease and stroke events occurred at a rate of 5.6% (n = 88) and 4.65% (n = 73). The independent predictors for NOD were age (OR = 1.026, p = 0.041), waist circumference (OR = 1.044, p < 0.001), family history of diabetes (OR = 2.173, p = 0.003) and systolic BP at follow-up (OR 1.022, p = 0.044). The presence of NOD was independently associated with greater incidence of stroke (HR 2.404, p = 0.046), along with age (HR 1.078, p < 0.001), duration of hypertension (HR 1.039, p = 0.017) and office systolic blood pressure at follow-up (HR 1.022, p = 0.026), whereas development of NOD had no relationship with the incidence of coronary artery disease. CONCLUSIONS: Our findings indicate the high incidence of NOD and its close association with stroke in essential hypertension. Poorer control of hypertension appears to be a common denominator of both NOD and stroke in this setting.

The dominant role of the systolic component of nondipping status on target-organ damage in never-treated hypertensives.

BACKGROUND: Blood pressure (BP) nondipping has been associated with target-organ damage (TOD) and adverse outcomes in hypertension. Diverse definitions of nondipping status appear in the literature, regarding the BP components taken into account. Aim of this study was to compare the effects of isolated nondipping of systolic, diastolic and combined systolic and diastolic BP on various indices of TOD. METHODS: From 630 consecutive subjects with never-treated essential hypertension stage I-II, we selected 279 subjects who were consistently isolated systolic nondippers (SND, n=76) isolated diastolic nondippers (DND, n=64) and combined systolic and diastolic nondippers (SDND, n=139) in two ambulatory BP monitoring sessions. All three subgroups were subjected to echocardiographic examination, carotid-femoral pulse wave velocity (PWV(c-f)) and albumin-to-creatinine ratio (ACR) determination. Metabolic profile was determined in a morning blood sample. RESULTS: SND compared to DND and SDND exhibited higher left ventricular mass/height(2.7) (42.4 ± 9.9 vs. 38.0 ± 9.1 vs. 40.9 ± 11.0 g/m(2.7), P < 0.05), higher log(10)(PWV(c-f)) (0.94 ± 0.07 vs. 0.86 ± 0.05 vs. 0.91 ± 0.07 m/s, P < 0.005), and higher log(10)(ACR) (1.2 ± 0.5 vs. 0.9 ± 0.3 vs. 1.1 ± 0.4 mg/g, P < 0.05). Isolated systolic BP nondipping was an independent determinant of all the studied indices of TOD whereas isolated diastolic BP nondipping was not. CONCLUSIONS: Isolated systolic as compared to diastolic and to combined systolic/diastolic BP nondipping is associated with higher left ventricular mass, stiffer arteries, and pronounced urinary albumin excretion.

Relationships of CRP and P wave dispersion with atrial fibrillation in hypertensive subjects.

BACKGROUND: Although inflammation has been shown to be implicated in the pathophysiology of atrial fibrillation (AF), little is known about its involvement in the accompanying atrial electrical remodeling expressed by P wave dispersion (P(disp)). METHODS: Fifty hypertensive subjects with documented paroxysmal AF (AF group) and 50 matched for body mass index, sex and office systolic blood pressure (BP) subjects with no history of AF (SR group) were subjected to electrocardiogram (ECG) and P(disp) assessment, hs-CRP determination, a complete echocardiographic study and 24-h ambulatory BP monitoring. RESULTS: The AF as compared to the SR subjects were older by 14 years (P < 0.0001) and they exhibited lower office and 24-h diastolic BP (7 mm Hg, P < 0.0001 and by 8 mm Hg, P < 0.0001, respectively) and higher office and 24-h pulse pressure (by 4 mm Hg, P = 0.03 and 6 mm Hg, P = 0.001, respectively) mean values. A higher mean of left atrial (LA) diameter index (by 1.9 mm/m(2), P < 0.0001) and left ventricular mass index (by 16 g/m(2), P < 0.0001) were observed in the AF vs. SR group. P(disp) mean and hs-CRP median values were higher in the AF group (by 22 ms, P < 0.0005 and by 4.63 mg/l, P < 0.0005, respectively). Standard multiple and multiple logistic regression analysis identified log(10)(hs-CRP) as independent determinant of P(disp) and log(10)(CRP) and P(disp) as independent determinants of AF. CONCLUSIONS: In hypertensive subjects hs-CRP and P(disp) are interrelated and associated with AF, suggesting an active implication of inflammation in the atrial electrophysiological remodeling predisposing to AF.

The conjoint detrimental effect of chronic periodontal disease and systemic inflammation on asymmetric dimethyl-arginine in untreated hypertensive subjects.

OBJECTIVE: To investigate the relationship between periodontal disease indexes (PDI) and endothelial dysfunction by means of asymmetric dimethyl-arginine (ADMA) in conditions of both increased and decreased systemic inflammation in the setting of hypertension. METHODS: We studied 108 - aged 52+/-9 years - untreated hypertensive subjects (24 h systolic/diastolic blood pressure [BP] 131+/-11/83+/-9 mmHg) with diverse severity of periodontal disease (i.e. mean clinical loss of attachment, maximum probe depth and gingival index). Subjects underwent office and ambulatory BP measurements, echocardiography, periodontal examination; while from fasting venous blood samples we assessed metabolic profile, and we measured ADMA and high sensitivity C reactive protein (hsCRP) levels. RESULTS: With respect to the median of hsCRP and ADMA (1.79 mg/l and 0.81 micromol/l, respectively) the study population was divided in four groups: low-ADMA/low-hsCRP (n=30), low-ADMA/high-hsCRP (n=27), high-ADMA/low-hsCRP (n=21) and high-ADMA/high-hsCRP (n=30). High-ADMA/high-hsCRP group resulted significantly older compared with both low-ADMA/low-hsCRP and high-ADMA/high-hsCRP groups, while high compared with low-ADMA groups demonstrated increased low-density lipoprotein cholesterol. PDIs were increased in those with high compared with those with low-hsCRP, while the addition of high-ADMA contributed significantly to that comparison. After adjustment for confounders, high-ADMA/high-hsCRP was significantly associated--by means of adjusted z-scores--with mean clinical loss of attachment, maximum probe depth and gingival index by 10.33, 8.84 and 2.74 times more often with respect to the low-ADMA/low-hsCRP pattern. CONCLUSION: PDI are associated in a dose-dependent manner with ADMA in untreated hypertensives and increased systemic inflammation further contributes to that phenomenon.

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.

Left ventricular hypertrophy versus chronic kidney disease as predictors of cardiovascular events in hypertension: a Greek 6-year-follow-up study.

OBJECTIVES: We assessed the comparative prognostic role of left ventricular hypertrophy (LVH) and chronic kidney disease (CKD) for major cardiovascular events in a prospective observational study in Greek essential hypertensive patients. METHODS: We followed up 1652 hypertensive patients (mean age 54.3 years, 696 male patients, office blood pressure 147/93 mmHg) free of cardiovascular disease for a mean period of 6 years. CKD and echocardiographically detected LVH were evaluated at baseline along with five major traditional risk factors [age > 65 years, sex, current smoking, diabetes mellitus and dyslipidemia (low density lipoprotein > 160 mg/dl)]. End points of interest were the incidence of coronary artery disease, stroke, all-cause mortality and their composite. RESULTS: At the end of follow-up, coronary artery disease was the most prevalent (5.2%), followed by stroke (5%) and total mortality (3.1%). The presence of both LVH and CKD is associated with a 2.5-fold increase in coronary artery disease (P = 0.034), four-fold in stroke (P = 0.002) and 3.2-fold in the composite (P < 0.001), whereas the presence of LVH alone was associated with a 2.5-fold higher risk for stroke (P = 0.009) and 1.7-fold for the composite (P = 0.018). By multivariate Cox regression analysis, LVH (hazard ratio = 1.53, P = 0.036) and CKD (hazard ratio = 1.66, P = 0.039) turned out to be independent prognosticators of the composite end point, whereas age more than 65 years (hazard ratio = 4.59, P < 0.001) and the presence of LVH (hazard ratio = 2.01, P = 0.043) were the only predictors of stroke. CONCLUSIONS: In hypertensive patients free of cardiovascular disease, CKD and LVH are both independent prognosticators of the composite end point of all-cause death and cardiovascular morbidity, whereas LVH but not CKD is a major predictor for stroke.

Impact of waist circumference on cardiac phenotype in hypertensives according to gender.

Our aim was to assess the differential effect of waist circumference on left-ventricular (LV) structural and functional alterations, in hypertensive males and females. One thousand seven hundred and eighty nine consecutive, nondiabetic, essential hypertensives (aged 55.8 +/- 13.5 years, 966 females), included in the 3H Study, an ongoing registry of hypertension-related-target-organ damage, were classified to obese and nonobese groups according to Adult Treatment Panel III criteria. All participants underwent complete echocardiographic study including LV diastolic function evaluation by means of conventional and tissue Doppler imaging (TDI) methods, averaging early and late diastolic mitral annular peak velocities (Em, Am, Em/Am) from four separate sites of measurement. Hypertensive obese women compared with nonobese exhibited significantly greater LV mass index and prevalence of LV hypertrophy (by 5.5 g/m(2), P = 0.003, and 8.8%, P = 0.005, respectively), while such differences were not present among men. Obese women compared to nonobese ones were accompanied by lower transmitral E/A (by 0.08, P < 0.001), TDI-derived Em/Am (by 0.12, P < 0.001), and higher E/Em ratio (by 0.8, P = 0.016). In contrast, hypertensive obese men compared to nonobese ones exhibited lower E and Em (by 0.04 m/s and 0.6 cm/s, both P < 0.05). A significant interaction between sex and abdominal obesity was observed only regarding TDI-derived Am and Em/Am. Furthermore, waist circumference was a predictor of E/A (beta = -0.097, P = 0.002) and Em/Am (beta = -0.116, P = 0.001), independently of body size, in females but not in males. The adverse effect of abdominal obesity on LV alterations is more pronounced among female hypertensives, suggesting that routine measurement of waist circumference provides additional information on cardiac phenotype especially in women.