Association between periodontal disease and its treatment,flow-mediated dilatation and carotid intima-media thickness: A systematic review and meta-analysis

Objective

This meta-analysis sought to investigate the association between carotid intima-media thickness (c-IMT), flow-mediated dilation (FMD) and periodontitis (PD) and to assess the effect of periodontal treatment on c-IMT and FMD.

Methods

Electronic database searching, hand searching of bibliographic references of included papers, related reviews, and journals in relation to oral, cardiovascular and ultrasound imaging field was carried out. Random effects meta-analyses were performed to investigate the association of co-existence of increased c-IMT, impaired FMD and PD with potential changes in these variables following periodontal intervention.

Results

2009 citations and 101 full text articles were screened, with 35 meeting the review inclusion criteria of which 22 suitable for quantitative analysis. Meta-analysis demonstrated that the diagnosis of PD was associated with a mean increase in c-IMT of 0.08 mm (95% C.I. = 0.07–0.09) and a mean difference in FMD of 5.1% compared to controls (95% C.I. = 2.08–8.11%). A meta-analysis of the effects of periodontal treatment on FMD showed a mean improvement of 6.64% between test and control (95% C.I. = 2.83–10.44%).

Conclusions

This review demonstrated an association between increased c-IMT, impaired FMD and PD. Data from intervention studies suggested a beneficial effect of periodontal treatment on FMD indicating an improvement in endothelial function. The findings support investigation of periodontitis treatment on cardiovascular outcomes.     

Flow-mediated changes in pulse wave velocity: a new clinical measure of endothelial function.

AIMS: To test whether measuring hyperaemic changes in pulse wave velocity (PWV) could be used as a new method of assessing endothelial function for use in clinical practice. METHODS AND RESULTS: Flow-mediated changes in vascular tone may be used to assess endothelial function and may be induced by distal hyperaemia, while endothelium-mediated changes in vascular tone can influence PWV. These three known principles were combined to provide and test a novel method of measuring endothelial function by the acute effects of distal hyperaemia on upper and lower limb PWV (measured by a recently developed method). Flow-mediated changes in upper and lower limb PWV were compared in 17 healthy subjects and seven patients with stable chronic heart failure (CHF), as a condition where endothelial function is impaired but endothelium-independent dilator responses are retained. Corroborative measurements of PWV and brachial artery diameter responses to endothelium-dependent and -independent pharmacological stimuli were performed in a further eight healthy subjects. Flow-mediated reduction of PWV (by 14% with no change in blood pressure) was found in normal subjects but was almost abolished in patients with CHF. PWV responses appear to be inversely related to and relatively greater than brachial artery diameter responses. CONCLUSION: The method may offer potential advantages of practical use and sensitivity over conduit artery diameter responses to measure endothelial dysfunction.     

Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population

Background and aims

Oxidative stress has been advocated as a major cause for cardiovascular disease (CVD), and low plasma antioxidant concentrations are associated with endothelial dysfunction, the first step towards atherosclerosis. However, although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD, supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk. The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation (FMD) in volunteers at low cardiovascular risk.

Methods and results

In a crossover trial, 24 subjects (13 women, mean age 61 ± 3 years), received, in a randomised order, a 14-day high (HT) and a 14-day low (LT) antioxidant diets, with a 2-week wash-out (WO) in between. Both diets were comparable in daily portions of fruits and vegetables, and in alcohol, fibre and macronutrient intake, but differed in their total antioxidant capacity. Before and after each diet, anthropometrics, blood pressure, fasting plasma glucose, lipid profile, hepatic enzymes, circulating antioxidant concentrations, high sensitivity C-reactive protein (hs-CRP) and FMD were assessed.FMD increased significantly during the HT diet compared to the LT (p < 0.000). FMD values were 2.3% higher after HT compared with LT (p < 0.001) after adjustment for age, gender and diet order. α-tocopherol increased significantly (p < 0.05) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly (p < 0.05 and p < 0.01, respectively) during the HT diet, compared with the LT diet.

Conclusions

A short-term HT diet improves endothelial function in volunteers at low cardiovascular risk, which may further reduce their risk of CVD.     

Assessment of endothelial function in complex regional pain syndrome type I

The objective of this study is to investigate the endothelial function in complex regional pain syndrome. A total of 21 patients with CRPS and 15 healthy controls were enrolled. The mean age of patients was 22 ± 4.9 years and the mean duration of the disease was 5.9 ± 2.5 months. Flow-mediated vasodilatation (FMD) technique was performed for evaluating the endothelial function. Parameters were the waveforms obtained and the increase in diameter and blood flow of the brachial artery, which were expressed as the percent change from baseline. The differences of the waveforms obtained in the affected limbs in comparison to non-affected limbs and to controls were statistically significant. We observed a trend of greater percent dilating responses in the affected limbs; however, the differences showed no statistical significance. In macrovascular evaluation, the endothelial function seems to be impaired in the earlier stage of the disease.     

The effects of hyperuricaemia on flow-mediated and nitroglycerin-mediated dilatation in high-risk patients

Background and aimsUric acid is emerging as one of the newer risk markers to consider in the cardiovascular risk assessment because it is demonstrated to be associated with adverse cardiovascular outcomes, particularly in high cardiovascular risk patients. One of the proposed mechanisms involving hyperuricaemia is the development of vascular damage. The aim of this study is to examine the role of hyperuricaemia on vascular function in patients with high cardiovascular risk.Methods and resultsWe examined the clinical significance of hyperuricaemia in relation to vasomotor response of the brachial artery by using high-resolution ultrasound in 304 subjects with coronary artery disease and/or diabetes. Nitroglycerin-mediated dilatation (NMD) was significantly lower in the hyperuricaemic group compared with the normouricaemic group (12.8  ±  6.9% vs. 16.2  ±  7.7%, p < 0.001), but no significant difference was observed in flow-mediated dilatation (FMD) between the two groups [3.78 (95% CR: 1.5–9.9) vs. 3.88 (95% CR: −2.6 to 9.9), p = 0.78]. Multivariate analysis demonstrated that smoking was the strongest predictor of FMD (b = −0.81, p = 0.02); and that smoking (b = −2.62, p = 0.003), SBP (b = −0.11, p = 0.001), hyperuricaemia (b = −2.11, p = 0.02) and use of nitrates (b = −3.30, p = 0.001) were independent predictors of NMD.ConclusionHigh cardiovascular risk patients with hyperuricaemia had a lower NMD than those with normouricaemia. Importantly, hyperuricaemia was independently associated with NMD after multivariable adjustments. To further understand the pathophysiological mechanisms involving hyperuricaemia, particularly in the context of impaired NMD, further experimental and clinical studies are needed.     

Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure

Background and Aims

Flow-mediated dilatation of the brachial artery (FMD) is a biomarker of endothelial function and cardiovascular health. Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity. Various food ingredients such as polyphenols have been shown to improve FMD. We investigated whether consuming resveratrol, a polyphenol found in red wine, can enhance FMD acutely and whether there is a dose-response relationship for this effect.

Methods and Results

19 overweight/obese (BMI 25–35 kg m⁻²) men or post-menopausal women with untreated borderline hypertension (systolic BP: 130–160 mmHg or diastolic BP: 85–100 mmHg) consumed three doses of resveratrol (resVida™ 30, 90 and 270 mg) and a placebo at weekly intervals in a double-blind, randomized crossover comparison. One hour after consumption of the supplement, plasma resveratrol and FMD were measured. Data were analyzed by linear regression versus log₁₀ dose of resveratrol. 14 men and 5 women (age 55 ± 2 years, BMI 28.7 ± 0.5 kg m⁻², BP 141 ± 2/89 ± 1 mmHg) completed this study. There was a significant dose effect of resveratrol on plasma resveratrol concentration (P < 0.001) and on FMD (P < 0.01), which increased from 4.1 ± 0.8% (placebo) to 7.7 ± 1.5% after 270 mg resveratrol. FMD was also linearly related to log₁₀ plasma resveratrol concentration (P < 0.01).

Conclusion

Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner. This effect may contribute to the purported cardiovascular health benefits of grapes and red wine.     

Reduced flow-mediated vasodilation of brachial artery in children with primary snoring

Background

Sleep disordered breathing, especially obstructive sleep apnea, is associated with endothelial dysfunction in both adults and children. However, the role of primary snoring (PS) on endothelial function has not been investigated. This study aimed to examine flow-mediated vasodilation (FMD) in both normal weight and overweight children with PS.

Methods

Children aged 6–18 years with habitual snoring were recruited from our sleep disorder clinic. Non-snoring controls were recruited from participants of a community growth survey. All subjects underwent polysomnography and FMD evaluation on the same day. Children with body mass index of greater than the 85th percentile of the local reference were defined as overweight. Subjects were divided into groups of normal weight, overweight, non-snorers and PS for comparisons.

Results

Two hundred and one children, of whom 83 were overweight, with a mean ± SD age of 11.3 ± 2.7 years were recruited. Seventy three out of 201 children had PS. Both normal weight (7.9 ± 1.3 vs. 8.5 ± 0.9, p = 0.012) and overweight subjects (7.4 ± 1.4 vs. 8.1 ± 1.1, p = 0.006) with PS had significantly reduced FMD than the non-snoring controls. Multivariate linear regression model showed that PS was independently associated with reduced FMD in both normal weight (p = 0.014) and overweight subgroups (p = 0.016) after controlling for obstructive apnea hypopnea index.

Conclusions

PS in children is associated with reduced FMD, independent of obesity.     

Myocardial contrast echocardiography in biopsy-proven primary cardiac amyloidosis

Cardiac vasculature is affected in 88–90% of patientswith primary cardiac amyloidosis (CA). Myocardial contrast echocardiography(MCE) relies on the ultrasound detection of microbubble contrastagents that are solely confined to the intravascular space,and are therefore useful in the evaluation of flow in the microvasculature.This is the first case report describing the use of MCE duringvasodilator stress to evaluate coronary flow reserve in a patientwith biopsy-proven primary CA and angiographically normal coronaries.Qualitative MCE demonstrated delayed replenishment of microbubblesduring peak stress; quantitative analysis was consistent witha reduction in total myocardial blood flow and reserve values.Comparative imaging modalities including strain and strain rateimaging, magnetic resonance imaging, and myocardial scintigraphywere suggestive to the diagnosis of CA. In conclusion, MCE isa method for recognition of microvascular dysfunction, and mightbe considered as a useful tool to augment echocardiographicassessment in the early diagnosis of CA.     

Obstructive intramural coronary amyloidosis and myocardial ischemia are common in primary amyloidosis

Purpose

The purpose of this study was to determine the prevalence of clinical syndromes and pathologic changes of myocardial ischemia due to obstructive intramural coronary amyloidosis among patients with primary amyloidosis and cardiac involvement.

Subjects and methods

Medical records and pathologic specimens were reviewed from 96 patients with primary amyloidosis and cardiac involvement at autopsy or after cardiac transplantation during a 20-year period. Medical records were reviewed for patient demographic and clinical characteristics, including evidence for syndromes of myocardial ischemia. Pathologic specimens were examined for obstructive intramural coronary amyloidosis and microscopic changes of myocardial ischemia.

Results

Obstructive intramural coronary amyloidosis was present in 63 of 96 patients (66%). Microscopic changes of myocardial ischemia were more common in patients with obstructive intramural coronary amyloidosis (86%) than in those without (52%) (P <.001). In the 76 patients without coexistent severe epicardial coronary atherosclerosis, changes of myocardial ischemia were more common in those with obstructive intramural coronary amyloidosis (83%) than in those without (45%) (P <.001). In patients who had tissue available for review, none had obstruction of epicardial coronary arteries from amyloid. Syndromes of myocardial ischemia affected 16 patients (25%) with obstructive intramural coronary amyloidosis but only 2 patients (6%) without (P = .027). For 11% of the patients with obstructive intramural coronary amyloidosis, a syndrome of myocardial ischemia consisting of acute myocardial infarction or angina pectoris was the first manifestation of primary amyloidosis.

Conclusion

Most patients with primary systemic amyloidosis and cardiac involvement have obstructive intramural coronary amyloidosis and associated microscopic changes of myocardial ischemia. Syndromes of myocardial ischemia may occur in these patients.     

Unusual CD4+CD28− T lymphocyte subset is implicated in the pathogenesis of early atherosclerosis in patients with rheumatoid arthritis

Background

Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis which is not fully explained by traditional risk factors. Such excess risk appears to be driven by systemic inflammation.

The indexes of arterial structure and function in women with simple obesity: a preliminary study

Obesity is associated with an increased risk of cardiovascular disorders. The aim of the present study was to compare the indexes of arterial structure and function in women with simple obesity and healthy individuals. Twenty-two women with simple obesity (body mass index [BMI]: 33.6 +/- 2.9 kg/m(2), age: 29.7 +/- 6.2 years), and 34 healthy women were included in the study. Healthy subjects were divided into two subgroups according to their age (<35 and >45 years): Control A-16 young women (age <35 years, BMI: 24.0 +/- 3.0 kg/m(2)), and Control B-18 older women (age >45 years, BMI: 25.8 +/- 2.9 kg/m(2)). Noninvasive, high-resolution, vascular ultrasound was used to evaluate the endothelial-dependent vasodilatation: flow-mediated dilatation of brachial artery (FMD); the arterial structure: intima-media thickness (IMT) of common carotid artery (CCA); and the compliance parameters corresponding to structural changes in large arteries (PWV: pulse wave velocity; PP: pulse pressure; TAC: total arterial compliance; Ao C: aorta compliance, CCA C: CCA compliance, stiffness indexes). Endothelial-dependent vasodilatation as represented by FMD was comparable in the obese group (16.8% +/- 7.9%; median: 15.5%) and healthy subjects (Control A: 14.1% +/- 4.7%; median: 13.6%; Control B: 13.9% +/- 6.5%; median: 13.0%). The mean value of IMT was significantly increased (P < 0.05) in Control B group (0.67 +/- 0.07 mm) in comparison to both obese patients (0.58 +/- 0.09 mm) and Control A group (0.53 +/- 0.05 mm). The compliance parameters (PWV, AoC, CCA C, stiffness indexes) were impaired in obese patients and Control B patients as compared to Control A individuals. PWV and stiffness indexes were significantly increased, and the AoC, CCA C-diameter, CCA C-area were significantly decreased. Simple obesity constitutes an important risk factor accelerating arterial stiffness in women.     

Diaphragm paralysis in primary systemic amyloidosis

A patient with primary (AL) systemic amyloidosis developed mononeuropathy multiplex complicated by diaphragmatic failure. High dose melphalan and autologous stem cell transplantation did not ameliorate neuropathy or diaphragm dysfunction. Nocturnal non-invasive ventilation lowered arterial carbon dioxide levels and improved daytime dyspnea. This is the first case associating AL amyloid-induced neuropathy with diaphragm dysfunction.     

Impairment of flow-mediated vasodilatation of brachial artery in patients with Cushing's Syndrome

Background Cushing’s Syndrome (CS) is associated with excess and premature cardiovascular disease. Endothelial dysfunction is the initiating event in the development of atherosclerosis. Endothelial function is assessed by flow-mediated dilatation (FMD) of brachial artery. The aim of this study was to assess FMD in patients with CS. Methods We prospectively evaluated 22 patients with CS (12 women, 10 men; aged 42 ± 11 years, serum cortisol 28.2 ± 14 μg/dl, 24-h urinary free cortisol (UFC) 269 ± 92 μg/day), and 23 control subjects (13 women, 10 men; aged 43 ± 10 years, serum cortisol 14 ± 4 μg/dl, 24 h cortisol 60 ± 22 μg/day). Endothelial function, measured as FMD of the brachial artery using ultrasound, was calculated in two groups. Endothelial function was evaluated by assessing 1-min postischemic FMD of the brachial artery. Results FMD was lower in patients with CS than that in those without (11.7 ± 4.8% vs. 15.8 ± 3.2%, P = 0.0001, respectively). There was no significant difference between two groups regarding baseline diameter of brachial artery. But, hyperemia diameter was lower in patients with CS than without CS (3.6 ± 0.22 mm vs. 3.9 ± 0.19 mm, P = 0.04, respectively) Conclusion Endothelium-dependent FMD may impair in patients with CS compared to controls. Measurement of endothelial function may identify high-risk individuals early and therapy to reduce or retard endothelial dysfunction in patients with CS may lead to decreased cardiovascular morbidity and mortality.     

Vascular dysfunction and its recovery after transradial coronary angioplasty- A serial observational study

ObjectiveTo serially evaluate the effect of trans-radial coronary angioplasty (TRA) on the vascular function of radial artery (RA) and upstream brachial artery (BA) and to find out the relative contribution of endothelial dependent flow-mediated vasodilatation (FMD) and endothelial independent nitrate mediated dilatation (NMD).MethodsForty patients of chronic stable angina with successful TRA were studied. FMD and NMD of bilateral RA and BA were measured with high-resolution ultrasound, before and at 24 h and at 3 months, after catheterization.ResultsFMD as well as NMD were significantly decreased in right RA (16.3 ± 3.6% to 5.7 ± 1.8%; p = 0.001, and 24.1 ± 5.3% to 9.7 ± 2.8%; p = 0.001, respectively) as well as in upstream BA (17.0 ± 1.6% to 9.4 ± 0.5%; p = 0.001,and 26.5 ± 6.8% to 20.5 ± 3.7%; p = 0.001, respectively) at 24 h. FMD/NMD ratio was also decreased in RA (70 ± 10% to 60 ± 10%; p = 0.04) and as well as in BA (70 ± 20% to 50 ± 10%; p = 0.03). The endothelial dysfunctions returned to normal at 3 months. Control arm did not show any change in vascular function at any point of time. Radial artery diameter/sheath ratio <1 and catheter exchanges >2 were the independent predictors for >50% decrease in FMD.ConclusionsTRA results in reversible depression in FMD as well as NMD in the radial artery as well as upstream brachial artery. These vascular dysfunctions are limited to the catheterized arm only and return to normal after 3 months.     

Left atrial myopathy in cardiac amyloidosis: implications of novel echocardiographic techniques.

AIMS: To assess left atrial (LA) function and determine the prevalence of LA dysfunction in AL amyloidosis (AL) using conventional and strain echocardiography. METHODS AND RESULTS: LA ejection fraction, LA filling fraction, LA ejection force, peak LA systolic strain rate (LAsSR), and LA systolic strain (LA epsilon) were determined in 95 AL patients (70 with and 25 without echocardiographic evidence of cardiac involvement, abbreviated CAL and NCAL, respectively), 30 age-matched controls (CON), and 20 patients with diastolic dysfunction and LA dilatation (DD). Peak LAsSR >2 standard deviations below mean CON value was used as the cut-off for normal LA function. LA ejection fraction was lower in CAL when compared with CON (40.4+/-13.6 vs. 67.0+/-6%, P=0.01). Left atrial septal strain rate and strain were lower in CAL (0.8+/-0.5 s(-1) and 5.5+/-4%, respectively) compared with CON (1.8+/-0.8 s(-1) and 14+/-4%, respectively, P=<0.0001), NCAL (1.6+/-0.8 s(-1) and 13+/-7%, respectively, P<0.0001) and DD (1.3+/-0.4 s(-1) and 10+/-2%, respectively, P<0.0001). Based on peak LA systolic strain rate criteria, the cut-off values for normal LA function were -1.1 s(-1) and -1.05 s(-1) for lateral and septal walls. Using these criteria, LA dysfunction was identified in 32% (lateral LA criteria) and 60% (septal LA criteria) of CAL patients. Lateral and septal LAsSR were lower in CAL patients with vs. those without symptoms of heart failure. Inter- and intra-observer agreement was high for LA strain echocardiography. CONCLUSION: LA function assessment using strain echocardiography is feasible with low intra- and inter-observer variability. LA dysfunction is observed in AL patients without other echocardiographic features of cardiac involvement and may contribute to cardiac symptoms in CAL.     

Increased prevalence of subclinical atherosclerosis in ankylosing spondylitis

ObjectivesThe increased risk of atherosclerosis in inflammatory rheumatic diseases like rheumatoid arthritis and systemic lupus erythematosus has been established in various studies. However, similar studies in ankylosing spondylitis (AS) have yielded conflicting results. We studied subclinical atherosclerosis and endothelial dysfunction sonographically in AS patients and compared the results with matched healthy controls.MethodsFifty AS patients and 50 age and sex matched controls were recruited. However, 45 AS patients (28.6 ± 8.2 years; 42 males and 3 females) and 42 healthy controls (29.6 ± 8.6 years; 38 males and 4 females) were studied, as the others were excluded because of dyslipidemia. Height, weight, and waist circumference measurements were taken. Flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness of the common carotid artery (CIMT) and ankle-brachial index (ABI) were measured sonographically.ResultsAS patients had significantly higher CIMT compared to controls (0.56 ± 0.1 mm in AS patients and 0.51 ± 0.08 mm in controls; p = 0.03). FMD was lower in AS patients (14.1 + 9.7%) as compared to controls (18.1 + 8.7%; p = 0.04) and ABI was higher in patients (1.16 + 0.1) as compared to controls (1.1 + 0.1; p = 0.05) 20% of AS cases had impaired FMD (defined as a FMD <4.5%) compared to none among the controls (p = 0.03).ConclusionsThis study revealed an increased prevalence of subclinical atherosclerosis in AS patients.     

New therapeutic approaches in primary systemic AL amyloidosis

Received: April 9, 1999 / Accepted: September 6, 1999     

隐性高血压患者内皮依赖性血管舒张功能的变化

目的探讨隐性高血压患者肱动脉血流介导的内皮依赖性血管舒张功能(FMD)的变化及其影响因素。方法根据动态血压和诊室偶测血压将研究对象分为隐性高血压组(n=32)、原发性高血压(EH)组(n=30)和正常血压组(n=30)。所有入选者均通过超声测定肱动脉FMD和颈动脉内膜中层厚度(I MT),并测定血清生化指标及高敏C反应蛋白(hsCRP)。结果隐性高血压组(6.3±3.5)%和EH组的FMD(6.1±2.8)%均低于正常血压组(8.4±4.8)%(均P<0.05),但隐性高血压组和EH组患者FMD无显著性差异(P>0.05);隐性高血压组、EH组和正常血压组的I MT分别为(0.58±0.12)、(0.62±0.12)和(0.42±0.09)mm,3组比较,差异有统计学意义(P<0.01),隐性高血压组和EH组I MT无显著性差异(P>0.05);直线相关分析显示隐性高血压组患者FMD与I MT具有直线负相关(r=-0.59,P<0.01);多因素Logistic回归分析显示空腹血糖(OR=4.3,95%CI1.01～18.08)、hsCRP(OR=4.1,95%CI1.02～16.2)和白昼平均收缩压(dSB...     

A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis

Interleukin (IL)-6 is a pleiotropic proinflammatory cytokine involved in the pathogenesis of both atherosclerosis and rheumatoid arthritis. The role of the IL-6/IL-6 receptor pathway in the documented acceleration of atherosclerosis in rheumatoid arthritis has not been examined. In a non-randomized prospective pilot study we asked whether endothelial dysfunction, defined as impaired flow mediated dilatation (FMD), and aortic stiffness, assessed by pulse wave velocity (PWV) improve after 3 and 6 monthly therapeutic infusions of the anti-IL-6 receptor antibody tocilizumab for active rheumatoid arthritis. We found that FMD increased from 3.3 ± 0.8 to 4.4 ± 1.2 to 5.2 ± 1.9% (p = 0.003), whereas PWV decreased from 8.2 ± 1.2 to 7.7 ± 1.3 to 7.0 ± 1.0 m/s (p < 0.001). Whether these beneficial arterial changes are direct effects of the IL-6/IL-6 receptor pathway inhibition, maintained over time and translate into better clinical outcome warrants further studies.