High platelet reactivity is associated with vascular function in patients after percutaneous coronary intervention receiving clopidogrel

Background

In the present study, we evaluated the association of platelet reactivity with vascular function in patients after percutaneous coronary intervention receiving clopidogrel treatment.

Methods

We enrolled 150 patients with stable CAD receiving clopidogrel regimen (75 mg/d), 1 month after percutaneous coronary intervention. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as an index of arterial wave reflections. High on treatment platelet reactivity (HPR) was evaluated using VerifyNow Assay. VerifyNow reports its results in P2Y12 reaction units (PRU), and the diagnostic cutoff value is 230 PRU. Patients were evaluated prospectively up to 24 months. The primary end point was a composite of death from cardiovascular causes, nonfatal major cardiovascular events and hospitalization for cardiovascular causes.

Results

There was no difference in the basic clinical and demographic characteristics between subjects with HPR and non-HPR. Subjects with high on treatment platelet reactivity and PRU > 230 had significantly increased PWV (8.81 ± 2.25 m/s vs. 7.69 ± 1.95 m/s, p = 0.001) and AIx (25.27 ± 8.67% vs. 20.87 ± 10.57%, p = 0.04) compared to subjects with PRU ≤ 230. PWV was also associated with PRU (r = 0.23, p = 0.02). HPR was associated with significantly increased risk of primary end point [HR = 5.38, 95%CI:(1.15, 26.04), p = 0.03].

Conclusions

Increased platelet reactivity is associated with impaired arterial stiffness in patients after percutaneous coronary intervention receiving clopidogrel treatment, highlighting another clinical factor implicated in individual platelet response to antiplatelet therapy. Moreover, increased platelet reactivity is associated with adverse outcome in these patients.     

Impact of human immunodeficiency virus infection on arterial stiffness and wave reflections in the early disease stages

Background

Human immunodeficiency virus (HIV) infection is associated with subclinical inflammation and increased cardiovascular risk. Arterial stiffness and enhanced wave reflections are markers of cardiovascular disease and independent predictors of cardiovascular risk. The effect of HIV infection, per se, on aortic stiffness and wave reflections has not been clearly defined.

Methods

We studied 51 adults with a recent HIV infection, free of antiretroviral treatment and AIDS diagnosis, as well as 35 controls matched for age, sex and smoking status. Carotid-femoral pulse wave velocity (PWV) and timing of the reflected wave (Tr) were measured as indices of aortic stiffness, while aortic augmentation index (AIx) and augmented pressure (AP) were measured as indices of wave reflections.

Results

While PWV was similar in the two populations, Tr was significantly lower in HIV-infected subjects compared to controls (by 16.5 ms, p = 0.002). In addition, AIx and AP were decreased (by 6.4%, p = 0.048 and by 3.3 mmHg, p = 0.010, respectively) in subjects with HIV infection. Moreover, HIV-infected patients compared with controls had increased values of hs-CRP [1.37 (0.85-2.53) vs. 0.75 (0.41-1.90) mg/l, p = 0.007] and interleukin-6 [1.90 (0.91-3.9) vs. 1.28 (0.80-2.65) pg/ml, p = 0.048]. Tr was negatively correlated with hs-CRP (r = −0.283, p = 0.010) and interleukin-6 (r = −0.278, p = 0.018).

Conclusions

Our study provides evidence of decreased wave reflections and similar aortic stiffness, as assessed by PWV, in the early stages of HIV infection in treatment-naive patients compared to controls. Subclinical inflammation and resultant peripheral vasodilatation constitute potential mediators of the whole pathophysiological process.     

Maximum home systolic blood pressure is a useful indicator of arterial stiffness in patients with type 2 diabetes mellitus: Post hoc analysis of a cross-sectional multicenter study

Aims

Maximum (max) home systolic blood pressure (HSBP) as well as mean HSBP or HSBP variability was reported to increase the predictive value of target organ damage. Yet, the association between max HSBP and target organ damage in patients with type 2 diabetes has never been reported. The aim of this study was to investigate the association between max HSBP and pulse wave velocity (PWV), a marker of arterial stiffness which in turn is a marker of target organ damage, in patients with type 2 diabetes.

Methods

We assessed the relationship of mean HSBP or max HSBP to PWV, and compared area under the receiver-operating characteristic curve (AUC) of mean HSBP or max HSBP for arterial stiffness in 758 patients with type 2 diabetes.

Results

In the univariate analyses, age, duration of diabetes mellitus, body mass index, mean clinic systolic blood pressure (SBP), mean HSBP and max HSBP were associated with PWV. Multivariate linear regression analyses indicated that mean morning SBP (β = 0.156, P = 0.001) or max morning SBP (β = 0.146, P = 0.001) were significantly associated with PWV. AUC (95% CI) for arterial stiffness, defined as PWV equal to or more than 1800 cm per second, in mean morning SBP and max morning SBP were 0.622 (0.582–0.662; P < 0.001) and 0.631 (0.591–0.670; P < 0.001), respectively.

Conclusions

Our findings implicate that max HSBP as well as mean HSBP was significantly associated with arterial stiffness in patients with type 2 diabetes.     

Increased augmentation index is paradoxically associated with lower in-hospital mortality in patients with acute ischemic stroke

Objective

To evaluate the association between arterial stiffness and stroke severity and in-hospital outcome in patients admitted with acute ischemic stroke.

Methods

We prospectively studied 415 consecutive patients who were admitted with acute ischemic stroke (39.5% males, age 78.8 ± 6.6 years). On the third day of hospitalization, the following markers of arterial stiffness were recorded: central systolic blood pressure (cSBP), diastolic BP (cDBP), mean pressure (cMP), pulse pressure (cPP), augmentation index (AIx) and pulse wave velocity (PWV). The severity of stroke was assessed on admission with the National Institutes of Health Stroke Scale (NIHSS) score. The outcome was evaluated with rates of dependency at discharge (modified Rankin scale score between 2 and 5) and in-hospital mortality.

Results

None of the markers of arterial stiffness showed significant correlation with the NIHSS score on admission. However, there was a trend for an inverse correlation with AIx (r = −0.142, p = 0.064) and for a positive correlation with PWV (r = 0.235, p = 0.054). None of the markers of arterial stiffness differed between patients who were dependent at discharge and those who were independent. Patients who died during hospitalization had higher cDBP and cMP but lower cPP and AIx than patients who were discharged. In binary logistic regression analysis, independent predictors of in-hospital mortality were NIHSS score on admission (relative risk (RR) 1.16, 95% confidence interval (CI) 1.08–1.25, p < 0.001), presence of atrial fibrillation (RR 6.41, 95% CI 1.37–29.93, p = 0.018) and AIx (RR 0.94, 95% CI 0.89–0.99, p = 0.030).

Conclusions

Increased AIx appears to be associated with lower in-hospital mortality rates in elderly patients with acute ischemic stroke. Other markers of arterial stiffness do not appear to be associated with short-term outcome in this population.     

The impact of aerobic exercise training on arterial stiffness in pre- and hypertensive subjects: A systematic review and meta-analysis

Background

Debate concerning aerobic exercise decreasing arterial stiffness in pre- and hypertensive individuals still exists. We sought to systematically review and quantify the effect of aerobic exercise training on arterial stiffness in pre- and hypertensive subjects.

Methods

MEDLINE, Cochrane, Scopus and Web of Science were searched up until August 2013 for trials assessing the effect of aerobic exercise interventions lasting 4 or more weeks on arterial stiffness in (pre)hypertensive subjects. Standardized mean difference (SMD) in arterial stiffness parameters (PWV, B-stiffness, Compliance, AIx) was calculated using a random-effects model. Subgroup and meta-regression analyses were used to study potential moderating factors.

Results

Fourteen trials comprising a total of 472 (pre)hypertensive subjects met the inclusion criteria. Arterial stiffness was not significantly reduced by aerobic training in (pre)hypertensive subjects (14 trials, SMD = − 0.19; P = .06). Likewise, post-intervention arterial stiffness was similar between the aerobic exercise-trained and control (pre)hypertensive subjects (8 trials, SMD = − 0.10; P = .43). Neither heterogeneity nor publication bias was detected in either of these analyses. In the subgroup analyses, arterial stiffness was significantly reduced in aerobic exercise-trained (pre)hypertensive subgroups below the median value in post minus pre-intervention systolic blood pressure (SBP) (SMD = − 0.38, P = .04) and in subgroups above the median value in the duration of the intervention (SMD = − 0.28, P = .03). Similar results were obtained in the meta-regression analysis.

Conclusions

Arterial stiffness is not reduced in (pre)hypertensive subjects in response to aerobic training unless associated with a substantial reduction in SBP and/or prolonged duration.     

Improvement in arterial stiffness following cardiac rehabilitation

Background

Exercise has been shown to beneficially alter arterial stiffness in selected clinical settings. However, the effects of a standardized exercise protocol – “cardiac rehabilitation (CR)” – on measures of arterial stiffness in patients with established coronary heart disease (CHD) has not been well studied.

Methods

Using applanation tonometry, we studied arterial vascular properties in 26 men and 22 women (mean age 60.5 ± 10.8 years) with established CHD over a 20 week CR program. All patients continued to receive their anti-anginal and vasoactive medications. In addition to standard hemodynamics we estimated central aortic pressure, central arterial pulsatility, augmentation index and arterial pulse wave velocity (PWV).

Results

After 20 weeks of CR, there were no significant changes in resting heart rate or peripheral blood pressure. In 33 patients with at least two follow-up visits, central aortic systolic pressure was consistently lower than peripheral arterial blood pressure and decreased over the CR program time (baseline, 109 ± 16 mm Hg; final, 105 ± 14 mm Hg. p = 0.01). Both carotid–radial (n = 12) and carotid–femoral (n = 21) — derived PWV decreased over the CR program (carotid–radial: baseline, 7.3 ± 1.2 m/s; final, 6.6 ± 1.2 m/s, p = 0.028. carotid–femoral: baseline, 7.2 ± 1.4 m/s; final, 6.5 ± 1.3 m/s, p = 0.02).

Conclusions

In this group of patients with established CHD, arterial PWV was noted to significantly decrease over a 20 week CR program. This change occurred in the absence of detectable changes in peripheral blood pressure or heart rate. Decreases in PWV may serve as a sensitive indicator of improved arterial stiffness in patients with atherosclerotic arterial disease notwithstanding ongoing medical therapy.     

Association of aortic stiffness with biomarkers of myocardial wall stress after myocardial infarction

Background

Aortic pulse wave velocity (PWV) was linked to LV-geometry and -function in patients with kidney disease and non-ischemic cardiomyopathy. The role of aortic compliance after acute STEMI is so far unknown. In the present study, we prospectively investigated the relationship of increased aortic stiffness with biomarkers of myocardial wall stress 4 months after STEMI.

Methods

48 STEMI patients who were reperfused by primary coronary angioplasty underwent cardiovascular magnetic resonance (CMR) at baseline and at 4-month follow-up. The CMR protocol comprised cine-CMR as well as gadolinium contrast-enhanced CMR. Aortic PWV was determined by velocity-encoded, phase-contrast CMR. Blood samples were routinely drawn at baseline and follow-up to determine N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a subgroup of patients, mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) levels were determined.

Results

Patients with a PWV above median (> 7.0 m/s) had significantly higher NT-proBNP, MR-proADM and MR-proANP concentrations at 4-month follow-up than patients with a PWV below median (all p < 0.02). PWV showed moderate to good correlation with NT-proBNP, MR-proAMD and MR-proANP levels 4 months after STEMI (all p < 0.05). Multivariate analysis revealed PWV, beside myocardial infarct size, as an independent predictor of 4-month NT-proBNP levels after correction for age, creatinine and LV ejection fraction (model r: 0.781, p < 0.001).

Conclusion

Aortic stiffness is directly associated with biomarkers of myocardial wall stress 4 months after reperfused STEMI, suggesting a role for aortic stiffness in chronic LV-remodelling.     

Pulse wave velocity is increased in patients with transient myocardial ischemia

OBJECTIVE: We have recently shown that mean pulse pressure is higher in patients with transient myocardial ischemia. Pulse pressure elevation might be an important consequence of increased arterial stiffness. The aim of this study was to prove if arterial stiffness is changed in patients with transient myocardial ischemia who bear a high cardiovascular risk. Additionally we investigated whether arterial stiffness or wave reflection is the best indicator for transient myocardial ischemia. Aortic pulse wave velocity (PWV) is a measure of arterial stiffness, and augmentation index (AIx) an indication of arterial wave reflection. Both are indicators for cardiovascular risk. METHODS: PWV (carotid-femoral) and AIx (SphygmoCor) were assessed in 74 hypertensive patients. Transient myocardial ischemia was detected using an ST-triggered 24-h ambulatory blood pressure monitoring device. RESULTS: ST-segment depressions were recorded in 30 of 74 patients. There were no significant differences with regard to age, mean arterial pressure, systolic blood pressure, diastolic blood pressure or heart rate. PWV was seen to be higher in patients with transient myocardial ischemia (10.6 versus 9.5 m/s, P = 0.036). There was no significant difference in AIx between the two groups. PWV (r = 0.36, P = 0.002) but not AIx correlated with pulse pressure. CONCLUSIONS: PWV is higher in hypertensive individuals (age > 60 years) with transient myocardial ischemia, suggesting that PWV is an indicator of increased cardiovascular risk. Although AIx is known to be associated with several cardiovascular diseases, it was not seen to be associated with silent myocardial ischemia. Our results suggest that the clinical significance of parameters of arterial stiffness and arterial wave reflection change with age, with a higher clinical importance of PWV indicated in patients over the age of 60.     

Central haemodynamics reveal significant potential for prevention in Black hypertensive patients born and living in sub-Saharan Africa

Background

Few studies assessed arterial stiffness in Black hypertensive patients born and living in sub-Saharan Africa, where cardiovascular disease reaches epidemic proportions.

Methods

The Newer versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial is currently recruiting native African patients to compare the efficacy of various antihypertensive drugs given once daily as single-pill combinations. Two centres engaged in pulse wave analysis and measured carotid-femoral pulse wave velocity (PWV). Statistical methods included single and multiple linear regressions.

Results

Of 172 patients screened, 116 entered the ancillary study on central haemodynamics (51.3% women; mean age 52.7 years; untreated blood pressure 147.6/87.1 mm Hg). The augmentation indexes were higher (p < 0.0001) in women than men, both peripherally (pAI, 11.1 vs. −10.6%) and centrally (cAI, 39.0 vs. 28.0%). PWV (8.91 m/s) and central pulse pressure (cPP, 48.7 mm Hg) were similar (p > 0.844) in both sexes. pAI and cAI increased with female sex and mean arterial pressure, but decreased with heart rate and body mass index. cPP increased with age and mean arterial pressure. PWV increased with age and mean arterial pressure. Patients with measurements above the age-specific thresholds determined in healthy Black South Africans amounted to 0 for cAI, 1 (1.2%) for cPP, and 11 (18.3%) for PWV.

Conclusion

NOAAH patients have measures of arterial stiffness similar to those of a healthy Black reference population with determinants as reported in the literature. Our observations highlight the potential for the prevention of irreversible arterial damage by timely treating sub-Saharan hypertensive patients to target blood pressure levels.     

Aortic biomechanics by magnetic resonance: Early markers of aortic disease in Marfan syndrome regardless of aortic dilatation?

Background

Previous studies demonstrated the usefulness of MRI in the evaluation of aortic biomechanics in Marfan patients with aortic dilatation. However, these parameters have not been well studied in earlier stages of aortic disease. The present work aimed to study aortic biomechanics: aortic distensibility (AD) and pulse wave velocity (PWV), by MRI in Marfan patients without advanced aortic disease.

Methods

Eighty consecutive Marfan patients were compared with 36 age- and sex-matched controls. MRI images at the level of ascending, descending and abdominal aorta were used to determine AD and PWV.

Results

Marfan patients (27 men; age: 32.0 ± 10.5 years; mean aortic root diameter: 37.2 ± 4.6 mm) had lower AD at all levels (ascending 2.6 ± 2.1 vs. 6.2 ± 3.7 mm Hg^− 1 · 10^− 3, p < 0.001; descending 3.1 ± 2.0 vs. 8.3 ± 4.2, p < 0.001; and abdominal 4.5 ± 2.2 vs. 14.0 ± 5.2, p < 0.001), higher aortic arch PWV (8.1 ± 6.5 vs. 4.3 ± 1.8 m/s, p < 0.01) and ascending-to-abdominal PWV (6.1 ± 3.0 vs. 4.7 ± 1.5 m/s, p < 0.01) compared with controls. Thirty-five Marfan patients had a non-dilated aortic root (mean aortic root diameter: 34.5 ± 3.8 mm). In multivariable analyses, after adjustment for age, pulse pressure and aortic dimensions, AD remained lower and PWV higher in Marfan patients; even Marfan patients with non-dilated aortic root showed impaired aortic biomechanics compared with controls. Z-score for ascending AD < − 3.5 distinguished Marfan patients from controls with 82.5% sensitivity and 86.1% specificity.

Conclusions

Aortic biomechanics by MRI were abnormal in the entire aorta in Marfan patients. Moreover, Marfan patients without dilated aortic root showed clear impairment of aortic biomechanics, which suggests that they may be used as early markers of aortic involvement in these patients.     

Ambulatory Recording of Wave Reflections and Arterial Stiffness during Intra- and Interdialytic Periods in Patients Treated with Dialysis

Background and objectives

Wave reflections and arterial stiffness are independent cardiovascular risk factors in ESRD. Previous studies in this population included only static recordings before and after dialysis. This study investigated the variation of these indices during intra- and interdialytic intervals and examined demographic, clinical, and hemodynamic variables related to arterial function in patients undergoing hemodialysis.

Design, setting, participants, & measurements

Between February 2013 and May 2014, a total of 153 patients receiving maintenance hemodialysis in five dialysis centers of northern Greece underwent ambulatory BP monitoring with the newly introduced Mobil-O-Graph device (IEM, Stolberg, Germany) over a midweek dialysis session and the subsequent interdialytic period. Mobil-O-Graph is an oscillometric device that records brachial BP and pulse waves and estimates, via generalized transfer function, aortic BP, augmentation index (AIx) as a measure of wave reflections, and pulse wave velocity (PWV) as an index of arterial stiffness.

Results

AIx was lower during dialysis than in the interdialytic period of dialysis-on day (Day 1) (mean±SD, 24.7%±9.7% versus 26.8%±9.4%; P<0.001). In contrast, PWV remained unchanged between these intervals (9.31±2.2 versus 9.29±2.3 m/sec; P=0.60). Both AIx and PWV increased during dialysis-off day (Day 2) versus the out-of-dialysis period of Day 1 (28.8%±9.8% versus 26.8%±9.4% [P<0.001] and 9.39±2.3 versus 9.29±2.3 m/sec [P<0.001]). Older age (odds ratio [OR], 1.09; 95% confidence interval [95% CI], 1.02 to 1.15), female sex (OR, 7.56; 95% CI, 1.64 to 34.81), diabetic status (OR, 8.84; 95% CI, 1.76 to 17.48), and higher mean BP (OR, 1.17; 95% CI, 1.09 to 1.27) were associated with higher odds of high AIx; higher heart rate was associated with lower odds (OR, 0.71; 95% CI, 0.63 to 0.80) of high AIx. Older age (OR, 2.04; 95% CI, 1.61 to 2.58) and higher mean BP (OR, 1.15; 95% CI, 1.05 to 1.27) were independent correlates of high PWV.

Conclusions

This study showed a gradual interdialytic increase in AIx, whereas PWV was only slightly elevated during Day 2. Future studies are needed to elucidate the value of these ambulatory measures for cardiovascular risk prediction in ESRD.     

Aortic surgery is one of the risk factors for enhancement of pressure wave reflection in adult patients with congenital heart disease

Background

: Excessive aortic pressure wave reflection is one of the risk factors of cardiovascular diseases. In some clinical course of congenital heart diseases, the elevated pressure wave reflection has been reported. The purpose of this study is to elucidate the risk factors of the enhanced pressure wave reflection in adult patients with congenital heart disease.

Methods

: We enrolled 99 adult (≥ 20 years) patients with congenital heart disease. We measured their radial pressure augmentation index and examined the relationship between it and various clinical variables.

Results

: The radial pressure augmentation index was 77.1 ± 19.1% and it had a significant correlation with the history of aorto-pulmonary shunt (t = 4.194; p < 0.0001), age (t = 4.091; p < 0.0001), height (t = − 3.580; p = 0.001) and the history of direct aortic surgery (t = 2.253; p = 0.027). Forty-four patients (44.4%) demonstrated high radial augmentation index (> 1 SD of age- and gender matched control) and the determinants of the elevated radial augmentation index were the history of aorto-pulmonary shunt (odds ratio, 21.32; 95% confidence interval, 5.47–83.14; p < 0.0001) and the direct aortic surgery (4.18; 1.38–12.72; p = 0.012).

Conclusions

: The history of aortic surgeries enhances aortic pressure wave reflection in adult patients with congenital heart disease. The enhanced aortic pressure wave reflection is one of the risk factors for cardiovascular diseases. Therefore, the adult patients with congenital heart disease after aortic surgeries should be carefully observed and tightly controlled concerning the risk factors for cardiovascular diseases.     

Concentric left ventricular remodeling and aortic stiffness: A comparison of obesity and hypertension

Background

Increased thoracic ascending aortic stiffness is thought to contribute to concentric left ventricular hypertrophy and increased mortality, a pattern seen in hypertension. As such, aortic stiffness and increased left ventricular mass are candidates by which obesity increases cardiovascular risk. However, obesity is characterized predominantly by increased abdominal aortic stiffness and with eccentric left ventricular hypertrophy.

Methods

We aimed to establish whether or not, in addition to these changes, there is also an element of concentric remodeling in obesity that was predicted by ascending aortic stiffness. 301 subjects underwent cardiovascular magnetic resonance imaging to measure regional aortic distensibility and left ventricular morphology. To compare obesity with hypertension, subjects were separated into groups by hypertensive status and body mass index.

Results

In comparison to normotensive subjects, hypertension was linked with concentric remodeling (a 17% increase in left ventricular mass:volume ratio (LVM:VR), (p < 0.001)) and reduced ascending aortic distensibility (by 64%,p < 0.001). LVM:VR was negatively correlated with ascending aortic distensibility (R = − 0.36,p < 0.01). Obesity, in the absence of hypertension, was associated with elevated left ventricular mass when compared to normal weight normotensive subjects (by 27%, p < 0.01), in an eccentric pattern with cavity dilatation (p < 0.01). However, LVM:VR was also 14% larger than in normal weight normotensive subjects (p < 0.01), indicative of additional concentric remodeling. LVM:VR in obesity was, however, not correlated with ascending aortic distensibility when adjusted for mean arterial pressure (R = − 0.14,p < 0.14).

Conclusion

In summary, despite the predominantly eccentric pattern of left hypertrophy in obesity there is a concentric element of hypertrophy that, unlike in hypertension, is not linked to increased ascending aortic stiffness.     

Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease

Background

Osteopontin (OPN) and osteoprotegerin (OPG) have recently emerged as key factors in both vascular remodeling and development of atherosclerosis. Arterial stiffness has an independent predictive value for cardiovascular events. We evaluate the relationship between OPG, OPN serum levels and vascular function in coronary artery disease (CAD) patients.

Methods

The study population was consisted of 409 subjects (280 with CAD and 129 without CAD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. OPG and OPN levels were measured, as markers of vascular remodeling and calcification, by ELISA. Gensini score was used to evaluate the extent of CAD.

Results

CAD patients, compared to those without CAD, had higher OPG (3.91 ± 1.87 pmol/l vs. 2.88 ± 1.32 pmol/l, p < 0.001) and logOPN levels (1.81 ± 0.18 ng/ml vs. 1.71 ± 0.24 ng/ml, p < 0.001) and impaired PWV (8.94 ± 2.21 m/s vs. 8.28 ± 1.91 m/s, p = 0.006). Furthermore, PWV was associated with serum OPG levels (r = 0.19, p < 0.001) and with serum logOPN levels (r = 0.10, p = 0.049). Multivariate linear regression analysis revealed that increased OPG (p = 0.013) and logOPN (p = 0.006) levels are associated with 3‐vessel CAD and Gensini score (p = 0.04 for OPG and p = 0.09 for OPN), independently of other known cardiovascular risk factors.

Conclusion

The present study revealed that serum OPG and OPN levels are positively associated with arterial stiffness, and with the extent of CAD. These preliminary results suggest that OPG and OPN levels are significantly correlated with vascular function contributing to the pathogenesis of atherosclerosis in CAD. Further studies are needed to explore the mechanisms of action of OPG and OPN in CAD.     

Associations between periodontal disease and cardiovascular surrogate measures among Indigenous Australians

Background/objectives

Inflammation is a key pathogenetic factor in atherogenesis. Periodontitis is a chronic inflammatory source which can have systemic impacts. Indigenous Australians have a higher prevalence of periodontal disease and experience cardiovascular disease earlier than non-Indigenous Australians. The aim was to describe the association between severity of periodontal inflammatory disease and measures of arterial structure and function.

Methods

Periodontal disease in a convenience sample of Indigenous Australians was assessed clinically; for those with periodontal disease, the extent of periodontal pockets ≥ 4 mm was stratified into quartiles. Vascular health was measured non-invasively via carotid-dorsalis pedis pulse-wave velocity (PWV), and via B-mode ultrasound of the common carotid intima-media (IMT). Non-fasting blood samples were collected for lipid and inflammatory marker evaluation. Linear regression models were constructed to determine the associations between extent of periodontal pocketing and vascular health, adjusting for traditional cardiovascular common risk factors.

Results

273 Indigenous Australian adults were recruited and complete data was available for 269 participants (154 males), median age 39 years. Arterial stiffness (PWV) significantly increased with increasing extent of periodontal pocketing (p trend = 0.001). By contrast, carotid IMT did not differ across quartiles.

Conclusions

Periodontal pocketing was associated with central arterial stiffness, a marker of presymptomatic arterial dysfunction, in Indigenous Australian adults with periodontal disease.     

Macrophage migration inhibitory factor is associated with vascular dysfunction in patients with end-stage renal disease

Background

Patients with end-stage renal disease (ESRD) show a high prevalence of cardiovascular disease with arterial stiffness, atherosclerosis and endothelial dysfunction, leading to increased morbidity and mortality. The cytokine macrophage migration inhibitory factor (MIF) exhibits proinflammatory and proatherogenic functions and has recently emerged as a major regulator of atherogenesis. Studies examining the relationship between circulating MIF levels and vascular dysfunction in this high-risk population do not exist.

Methods

In patients with ESRD (n = 39) and healthy controls (n = 16) we assessed endothelial function by flow-mediated dilation of the brachial artery and arterial stiffness (augmentation pressure, augmentation index and pulse pressure) using applanation tonometry. High-sensitive Troponin and subendocardial viability ratio were determined to assess myocardial injury.

Results

Patients with ESRD had impaired endothelial function and higher plasma MIF levels. MIF levels negatively correlated with endothelial function (r = − 0.345, P = 0.031) and positively with arterial stiffness indices in patients with ESRD (pulse pressure r = − 0.374, P = 0.019 and augmentation pressure r = − 0.423, P = 0.025). In multivariate regression models besides age, gender, weight, and heart rate, MIF was an independent predictor for arterial stiffness. Impact on myocardial end-organ damage was reflected by correlation with high-sensitive Troponin I (r = 0.43, P = 0.009).

Conclusion

Our findings show that high MIF plasma levels are associated with diminished endothelial function and arterial stiffness and are correlated with myocardial injury. Further studies are necessary to investigate whether modulation of MIF might have an impact on atherosclerotic disease in this high-risk population.     

MRI-assessed regional pulse wave velocity for predicting absence of regional aorta luminal growth in marfan syndrome

Background

In patients with Marfan syndrome (MFS), increased aortic wall stiffening may lead to progressive aortic dilatation. Aortic Pulse Wave Velocity (PWV), a marker of wall stiffness can be assessed regionally, using in-plane multi-directional velocity-encoded MRI. This study examined the diagnostic accuracy of regional PWV for prediction of regional aortic luminal growth during 2-year follow-up in MFS patients.

Methods

In twenty-one MFS patients (mean age 36 ± 15 years, 11 male) regional PWV and aortic luminal areas were assessed by 1.5 T MRI. At 2-year follow-up, the incidence of luminal growth, defined as mean luminal diameter increase > 2 mm was determined for five aortic segments (S1, ascending aorta; S2, aortic arch; S3, thoracic descending aorta, S4, supra-renal and S5, infra-renal abdominal aorta). Regional PWV at baseline was considered increased when exceeding age-related normal PWV (healthy volunteers (n = 26; mean age 30 ± 10 years, 15 male)) by two standard-errors. Sensitivity and specificity of regional PWV-testing for prediction of regional luminal growth were determined.

Results

Regional PWV at baseline was increased in 17 out of 102 segments (17%). Significant luminal growth at follow-up was reported in 14 segments (14%). The specificity of regional PWV-testing was ≥ 78% for all aortic segments, sensitivity was ≤ 33%.

Conclusions

Regional PWV was significantly increased in MFS patients as compared to healthy volunteers within similar age range, in all aortic segments except the ascending aorta. Furthermore, regional PWV-assessment has moderate to high specificity for predicting absence of regional aortic luminal growth for all aortic segments in MFS patients.     

Relationships between reduced heart rate variability and pre-clinical cardiovascular disease in patients with type 2 diabetes

Aims

Reduced heart rate variability (HRV), an early sign of diabetic cardiovascular autonomic neuropathy (CAN), is associated with worse cardiovascular outcomes. The objective was to evaluate relationships between HRV parameters and three pre-clinical cardiovascular disease markers (left ventricular hypertrophy [LVH], aortic stiffness and carotid atherosclerosis) in type 2 diabetes.

Methods

In a cross-sectional study, 313 patients with type 2 diabetes performed 24-h Holter monitoring, carotid ultrasonography (intima-media thickness and plaques measurements), aortic pulse wave velocity measurement and echocardiography (left ventricular mass index [LVMI] measurement). Time-domain HRV parameters were the standard deviation of all normal RR intervals (SDNN), the standard deviation of the averaged normal RR intervals for all 5 min segments (SDANN), the root mean square of differences between adjacent R-R intervals (rMSSD), and the percentage of adjacent R-R intervals that varied by >50 ms (pNN50). Multivariate linear and logistic regressions assessed associations between HRV parameters and the three markers of pre-clinical cardiovascular disease.

Results

Patients with reduced HRV had longer diabetes duration, greater prevalences of microvascular complications, lower physical fitness, and higher heart rate, glycated hemoglobin, albuminuria and LVMI than patients with normal HRV. On multivariate regressions, after adjustments for several confounders, reduced SDNN and SDANN were independently associated with LVH and aortic stiffness. No HRV parameter was associated with carotid atherosclerosis.

Conclusions

Two reduced HRV parameters, SDNN and SDANN, which reflect cardiovascular autonomic imbalance, were associated with LVH and aortic stiffness, markers of pre-clinical cardiovascular disease. These findings may offer insights into physiopathological mechanisms linking CAN to worse cardiovascular prognosis.     

Inflammatory status, arterial stiffness and central hemodynamics in hypertensive patients with metabolic syndrome

Introduction

Inflammatory state is activated in metabolic syndrome and may explain part of the adverse prognosis of this entity. Arterial stiffness, central blood pressures and wave reflections are independent predictors of cardiovascular risk. This study investigates the relation between low-grade inflammation and arterial stiffness and central hemodynamics in patients with metabolic syndrome.

Methods

We studied 106 consecutive hypertensive patients with metabolic syndrome. Arterial stiffness was assessed by carotid-femoral (c-f) and carotid-radial (c-r) pulse wave velocity (PWV). Central blood pressures were evaluated by pulse wave analysis and heart rate corrected augmentation index (AIx₇₅) was used as a measure of wave reflections. White blood cell count (WBC), high sensitivity C-reactive protein (hsCRP) and fibrinogen were measured as inflammatory markers.

Results

In univariable analysis, PWVc-f correlated with both hsCRP (p < 0.01) and fibrinogen (p < 0.01), while PWVc-r correlated with hsCRP (p = 0.05). Regarding central blood pressures, aortic SBP correlated positively with hsCRP (p < 0.05) and marginally with fibrinogen (p = 0.06) and WBC (p = 0.08). Interestingly, no correlation was found between AIx₇₅ and any of these biomarkers. After adjustment for age, gender, smoking, mean arterial pressure, heart rate, waist circumference, glucose, total and HDL cholesterol, PWVc-f was independently related to hsCRP (p < 0.001) and fibrinogen (p < 0.01), while a marginal independent correlation was also found between PWVc-r and hsCRP (p = 0.06). Furthermore, aortic PP independently associated with fibrinogen (p < 0.05) whereas marginal associations demonstrated between aortic SBP and hsCRP and fibrinogen (p = 0.06 for both).

Conclusion

Inflammatory status is related to arterial stiffness and central blood pressures (but not to augmentation index) in hypertensives with metabolic syndrome. These findings may have implications for increased cardiovascular risk in these patients.     

Measurement accuracy of non-invasively obtained central blood pressure by applanation tonometry: A systematic review and meta-analysis

Background and objectives

Non-invasive methods based on applanation tonometry have been proposed to estimate central blood pressure. However, the accuracy of these methods hasn't been systematically examined.

Methods

We performed a systematic review and meta-analysis of studies comparing estimated and invasively measured central BP.

Results

Sufficient data were available in 22 studies for meta-analysis (857 subjects and 1167 measurements). Acquired arterial pressure waveforms in these studies were directly measured, calibrated to match invasive aortic mean BP and diastolic BP or calibrated to match brachial BP measured with a sphygmomanometer, cuff BP. Of the former 2 conditions, the errors of estimated central BP were small with a mean and standard deviation of difference − 1.1 ± 4.1 mm Hg (95% limits of agreement − 9.1–6.9 mm Hg) for central systolic BP; − 0.5 ± 2.1 mm Hg (− 4.6–3.6 mm Hg) for central diastolic BP; and − 0.8 ± 5.1 mm Hg (− 10.8–9.2 mm Hg) for central pulse pressure. However, the errors inflated to − 8.2 ± 10.3 mm Hg (− 28.4–12.0 mm Hg) for central systolic BP, 7.6 ± 8.7 mm Hg (− 9.5–24.6 mm Hg) for central diastolic BP, and − 12.2 ± 10.4 mm Hg (− 32.5–8.1 mm Hg) for central pulse pressure, when calibrated to cuff BP. The findings were still evident in subgroup analysis conducted with different central BP estimating methods and validated cuff BP monitors.

Conclusion

Present tonometry-based central BP estimating methods are acceptable in theory, with small errors. However, based on current available evidence, there is substantial room for improvement in measurement accuracy of central BP when cuff BP is used to calibrate the peripheral waveforms.