Increased Oral Dryness and Negative Oral Health-Related Quality of Life in Older People with Overweight or Obesity.

This cross-sectional study was to evaluate the association between the oral health-related quality of life (OHRQoL) of older Thai people with obesity and oral health indicators. General and oral conditions were assessed. Oral dryness was determined using the Xerostomia Inventory-11 (XI-11) and clinical oral dryness score (CODS). OHRQoL was evaluated by the oral health impact profile (OHIP-14). Participants were aged 60-86 years; 73 (59.3%) were overweight or obese, and 50 (40.7%) were normal weight. Older patients with obesity had almost four times the rate of hypertension (OR = 3.59; 95%CI:1.34-9.60; p = 0.002), more missing teeth (p = 0.025), and higher CODS (p = 0.014) than those without obesity. The total XI-11 scores were positively associated with the total CODS, after adjusting for BMI (r = 0.267, p = 0.003). Those with obesity had almost three times the tendency for a negative OHRQoL compared with the non-obese (OR = 2.73; 95%CI:1.12-6.71; p = 0.04). After adjusting for all related factors, the chances of predicting an OHIP-14 score of four based on obesity and total XI-11 score were 4.42 (95%CI:1.57-12.47; p = 0.005) and 1.11 (95%CI:1.02-1.20; p = 0.013), respectively. Obesity had an increasingly undesirable negative impact on the OHRQoL of older Thai people and was influenced by BMI and oral dryness.

Comparison of measured blood pressure levels, hypertension history, oral diseases, and associated factors among Thai dental patients.

PURPOSE: To compare blood pressure (BP), hypertension (HT) history, oral diseases, and potentially associated factors among dental patients in Thailand and explore the associations among them. METHODS: This study included 709 patients. Demographic data, BP levels, oral diseases, xerostomia, anxiety, depression, and associated factors were evaluated. RESULTS: One-third of the patients were male; patients with a history of HT were older than those without (P < 0.001). In total, 53 (7.5%) had such a history, and HT was controlled in 29 (54.7%) of them. Patients with possible HT (BP ≥140/90 mmHg; 94 in total, 13.3%) were five times more likely to have a definitive diagnosis of HT than those without possible HT (odd ratio [OR] = 4.95; 95% confidence interval [CI]: 2.76-8.87; P < 0.001). They also had an increased tendency to be taking antidyslipidemic (OR = 5.54; 95% CI: 2.90-10.60; P = 0.001) or antidiabetic (OR = 4.80; 95% CI: 1.91-12.08; P = 0.001) drugs. Male sex (ß = 0.156, P < 0.001), higher age (ß = 0.299, P < 0.001), higher body mass index (ß = 0.410, P < 0.001), and periapical tissue diseases (ß = 0.073, P = 0.019) were significantly associated with elevated systolic BP. Severe periodontitis (ß = 0.081, P = 0.023) and a comparable association pattern with systolic BP were related to diastolic BP. Multivariate analysis revealed no significant association between BP and tooth loss, xerostomia, smoking, education level, anxiety, or depression. CONCLUSION: Dentists play an essential role in screening for undiagnosed and uncontrolled HT. Significant associations were noted between oral inflammatory diseases and high BP.

Erratum: Suwattipong et al. Comparison of Point-of-Care Testing and Hospital-Based Methods in Screening for Potential Type 2 Diabetes Mellitus and Abnormal Glucose Regulation in a Dental Setting. Int. J. Environ. Res. Public Health 2021, 18, 6459.

In the original article [...].

Comparison of Point-of-Care Testing and Hospital-Based Methods in Screening for Potential Type 2 Diabetes Mellitus and Abnormal Glucose Regulation in a Dental Setting.

This study aimed to compare the screening methods between point-of-care (POC) testing and hospital-based methods for potential type 2 DM and abnormal glucose regulation (AGR) in a dental setting. A total of 274 consecutive subjects who attended the Faculty of Dentistry, Mahidol University, Bangkok, Thailand, were selected. Demographic data were collected. HbA1c was assessed using a finger prick blood sample and analyzed with a point-of-care (POC) testing machine (DCA Vantage®). Hyperglycemia was defined as POC HbA1c ≥ 5.7%. Random blood glucose (RBG) was also evaluated using a glucometer (OneTouch® SelectSimple™) and hyperglycemia was defined as RBG ≥ 110 mg/dl or ≥140 mg/dl. The subjects were then sent for laboratory measurements for fasting plasma glucose (FPG) and HbA1c. The prevalence of AGR (defined as FPG ≥ 100 mg/dl or laboratory HbA1c ≥ 5.7%) and potential type 2 DM (defined as FPG ≥ 126 mg/dl or laboratory HbA1c ≥ 6.5%) among subjects was calculated and receiver operating characteristic (ROC) analysis was performed using FPG and HbA1c for the diagnosis of AGR and potential type 2 DM. The prevalence of hyperglycemia defined as POC HbA1c ≥ 5.7%, RBG ≥ 110 mg/dl, and RBG ≥ 140 mg/dl was 49%, 63%, and 32%, respectively. After the evaluation using laboratory measurements, the prevalence of AGR was 25% and 17% using laboratory FPG and HbA1c criteria, respectively. Based on the ROC curves, the performances of POC HbA1c and RBG in predicting FPG-defined potential type 2 DM were high (AUC = 0.99; 95% CI 0.98-0.99 and AUC = 0.94; 95% CI 0.86-1.0, respectively) but lower in predicting AGR (AUC = 0.72; 95% CI 0.67-0.78 and AUC = 0.65; 95% CI 0.59-0.70, respectively). This study suggested that POC testing might be a potential tool for screening of subjects with potential type 2 DM in a dental setting.

Periodontal Treatment Improves Serum Levels of Leptin, Adiponectin, and C-Reactive Protein in Thai Patients with Overweight or Obesity.

Periodontitis and overweight or obesity independently change serum levels of leptin, adiponectin, and C-reactive protein (CRP). The aim of this study is to investigate the alterations of serum levels of leptin, adiponectin, and CRP after nonsurgical periodontal treatment (NSPT) in Thai patients with overweight or obesity (Owt/Ob) who did or did not exhibit severe periodontitis (SP) and normal weight (Nwt) patients with or without SP. Two hundred sixty patients were screened; 29 patients were included in this study. The study participants comprised 6 patients with Owt/Ob who exhibited SP, 11 patients with Owt/Ob who did not exhibit SP, 5 Nwt patients with SP, and 7 Nwt patients without SP. Periodontal disease status was evaluated; serum levels of leptin, adiponectin, and CRP were determined by enzyme-linked immunosorbent assay at baseline, as well as at 3 and 6 months after NSPT. At 3 months after NSPT, periodontal status was improved in all groups (p < 0.05), except Nwt patients without SP. Serum levels of leptin and CRP were significantly reduced, while serum levels of adiponectin were elevated after NSPT, regardless of bodyweight or waist circumference (p < 0.05). Improvement in serum levels of leptin after NSPT was also observed in the Nwt with SP group (p = 0.015); these levels did not significantly differ in Nwt patients without SP. NSPT reduces serum levels of leptin and CRP and enhances serum levels of adiponectin in Thai patients with Owt/Ob, irrespective of periodontitis severity. These results suggest a role for periodontal treatment in the systemic inflammatory response of Thai people with Owt/Ob.

Salivary and serum interleukin-17A and interleukin-18 levels in patients with type 2 diabetes mellitus with and without periodontitis.

OBJECTIVE: Interleukin (IL)-17A and IL-18 have been proposed to play important roles in periodontitis and type 2 diabetes mellitus (DM), but human data are conflicting. The present study aimed to investigate the roles of IL-17A and IL-18 in periodontitis and DM by measuring salivary and serum levels, respectively. MATERIALS AND METHODS: A total of 49 participants with type 2 DM and 25 control subjects without type 2 DM were recruited. A periodontal screening and recording (PSR) index (0, 1-2, 3, and 4) was used to classify whether these subjects had periodontitis. Salivary and serum IL-17A and IL-18 levels were measured by enzyme-linked immunosorbent assay. Multiple linear regression analyses were used to evaluate the associations between these cytokines and clinical parameters. RESULTS: Salivary IL-17A levels were not significantly different between patients with DM and controls, however, the levels were significantly higher in controls with periodontitis than those without periodontitis (p = 0.031). Salivary IL-17A levels were significantly associated with the PSR index (ß = 0.369, p = 0.011). Multiple linear regression analyses revealed the association of salivary IL-18 levels and fasting plasma glucose (ß = 0.270, p = 0.022) whereas serum IL-18 levels were associated with HbA1C (ß = 0.293, p = 0.017). No correlation between salivary and serum levels of IL-17A and IL-18 was found. CONCLUSION: Salivary IL-17A was strongly associated with periodontitis, whereas salivary IL-18 was associated with FPG and serum IL-18 was associated with HbA1C. These results suggest the role of these cytokines in periodontal inflammation and DM.

Increased Plasma Osteocalcin, Oral Disease, and Altered Mandibular Bone Density in Postmenopausal Women.

An association between oral diseases and postmenopausal status has been recognized. However, the relationship between all oral disease, mandibular bone density, health status, and osteocalcin (OCN) bone markers in postmenopausal dental patients has not been reported. This study was therefore to verify the differences in plasma OCN levels, dental, periodontal, and oral mucosal disease, and mandibular bone density alterations from panoramic radiograph and systemic parameters in postmenopausal women, compared to premenopausal women. Oral, radiographic, and blood examination were performed in 92 females. Dental, periodontal, and oral mucosal statuses were recorded. Health profile parameters were collected from medical charts. Plasma OCN was evaluated by enzyme-linked immunosorbent assay. Forty-two (45.7%) participants were postmenopausal with a higher median age (55 (51, 62) years) than the premenopausal group (43 (38, 45) years). Overweight or obesity, hypercholesterolemia, and impaired fasting blood sugar were more prevalent in postmenopause. The average postmenopausal OCN level (425.62 ng/mL) was significantly higher than the premenopausal group (234.77 ng/mL, p < 0.001). The average number of missing teeth, mean attachment loss, alveolar bone loss, periapical lesion count, and clinical oral dryness score were also significantly higher in postmenopause (p=0.008, < 0.001, 0.031, 0.006, and 0.005, respectively). However, mandibular bone density determined by mandibular cortical index was lower in postmenopause (p < 0.001). The panoramic mandibular index, mandibular cortical width, fractal dimension, and other oral mucosal disease did not differ between the groups. Postmenopause was associated with elevated plasma OCN (ß = 0.504, p < 0.001) when related covariates were adjusted. Elevated plasma OCN, oral mucosal dryness, high number of periapical radiolucencies and missing teeth, and lower mandibular bone density from panoramic radiograph were prevalent in postmenopausal women. Dentists should suspect an increased risk of low bone mineral density in postmenopausal patients who display these clinical and radiographic findings, and they should be referred for further examination. Plasma OCN may interconnect a relationship between postmenopausal status and the low mandibular bone density.

Correlation of plasma osteopontin and osteocalcin with lower renal function in dental patients with carotid artery calcification and tooth loss.

OBJECTIVES: To investigate plasma osteopontin (OPN) and osteocalcin (OCN) levels in dental patients with carotid artery calcification (CAC) and determine the correlations between these proteins and renal function and tooth loss. METHODS: The health parameters and number of teeth of 99 participants were recorded. Panoramic radiographs were taken for CAC evaluation, and OPN and OCN levels were measured. RESULTS: None of the participants had overt kidney disease, and 14 (14.14%) had CAC. The age, sex, and health profiles of patients with CAC were not different from those without CAC. The OPN and OCN levels in participants with CAC were higher than in those without (p = 0.026 and p = 0.025, respectively). The OPN levels were correlated with the estimated glomerular filtration rate (eGFR) (p = 0.021) and tooth loss (p = 0.027). The OCN levels were correlated with the eGFR (p = 0.002), tooth loss (p = 0.023), blood urea nitrogen (p = 0.040), and creatinine levels (p = 0.031). The median tooth loss in individuals with an eGFR <60 mL/min/1.73 m2 was higher than that of individuals with an eGFR ≥60 mL/min/1.73 m2 (p = 0.033). In individuals with CAC, tooth loss correlated more strongly with the eGFR, and the correlation between OPN and OCN levels was more apparent. CONCLUSION: Dental patients with CAC and increased tooth loss have a greater tendency for decreased renal function, which may be associated with OPN and OCN; thus, these patients should be referred for investigation.

Salivary and serum cystatin SA levels in patients with type 2 diabetes mellitus or diabetic nephropathy.

OBJECTIVE: To investigate putative salivary biomarkers for screening and diagnosis of type 2 diabetes mellitus and diabetic nephropathy. DESIGN: Saliva and serum samples were collected from 29 patients with type 2 diabetes, 20 patients with diabetic nephropathy, eight patients with non-diabetic induced nephropathy, and 25 healthy subjects. Initially, pooled unstimulated saliva samples from six sex- and age-matched healthy subjects and six patients with type 2 diabetes were subjected to two-dimensional gel electrophoresis, followed by mass spectrometry. Protein expression of cystatin SA in the saliva of patients with type 2 diabetes was further examined in saliva and serum using enzyme-linked immunosorbent assay (ELISA). RESULTS: Two-dimensional gel electrophoresis revealed upregulation of salivary cystatin SA in patients with type 2 diabetes. ELISA showed a weak trend of increasing salivary cystatin SA levels in patients with type 2 diabetes, compared with those levels in healthy subjects. When patients were stratified according to periodontal status, linear regression analyses revealed that salivary cystatin SA levels were associated with Periodontal Screening and Recording (PSR) index (ß = 0.297, p < 0.05) when the analysis was adjusted for age, sex, HbA1C, estimated glomerular filtration rate (eGFR), and number of teeth. Serum cystatin SA levels were negatively associated with eGFR (ß = -0.534, p < 0.0001) when the analysis was adjusted for age, sex, HbA1C, number of teeth, and PSR index. CONCLUSIONS: Salivary cystatin SA was associated with periodontal disease severity; moreover, serum cystatin SA levels could reflect kidney function.

Inverse Association of Plasma IgG Antibody to Aggregatibacter actinomycetemcomitans and High C-Reactive Protein Levels in Patients with Metabolic Syndrome and Periodontitis.

The association between clinically diagnosed periodontitis, a common chronic oral infection, and metabolic syndrome has been previously reported. The aim of this study was to investigate the association of plasma IgG levels against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia, C-reactive protein, and periodontal status with metabolic syndrome. Plasma IgG levels and C-reactive protein were measured by enzyme-linked immunosorbent assay, and salivary levels of A. actinomycetemcomitans and P. gingivalis were determined by quantitative real-time polymerase chain reaction. Among 127 individuals aged 35-76 years, 57 participants had metabolic syndrome and severe periodontitis, 25 had metabolic syndrome and an absence of severe periodontitis, 17 healthy individuals had severe periodontitis, and 28 healthy individuals were without severe periodontitis. Patients with metabolic syndrome had reduced humoral immune response to A. actinomycetemcomitans (p = 0.008), regardless of their salivary levels or periodontitis status compared with healthy participants. The IgG antibody response to P. gingivalis, regardless of their salivary levels or participants' health condition, was significantly higher in severe periodontitis patients (p<0.001). Plasma IgG titers for P. intermedia were inconsistent among metabolic syndrome or periodontal participants. Our results indicate that the presence of lower levels of IgG antibodies to A. actinomycetemcomitans (OR = 0.1; 95%CI 0.0-0.7), but not P. gingivalis, a severe periodontitis status (OR = 7.8; 95%CI 1.1-57.0), high C-reactive protein levels (OR = 9.4; 95%CI 1.0-88.2) and body mass index (OR = 3.0; 95%CI 1.7-5.2), are associated with the presence of metabolic syndrome. The role of the decreased IgG antibody response to A. actinomycetemcomitans, increased C-reactive protein levels on the association between periodontal disease and metabolic syndrome in a group of Thai patients is suggested.

Effect of Periodontitis on Adiponectin, C-Reactive Protein, and Immunoglobulin G Against Porphyromonas gingivalis in Thai People With Overweight or Obese Status.

BACKGROUND: Obesity and periodontitis are associated with an inflammatory background. Inflammatory mediators involved may have reciprocal effects on one another. In this study, the levels of inflammatory mediators implicated in overweight or obese status and periodontitis are simultaneously evaluated. METHODS: Body mass index (BMI) and waist circumference, periodontal disease status, and plasma levels of adiponectin, leptin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule 1, C-reactive protein (CRP), immunoglobulin (Ig)G antibody against Porphyromonas gingivalis, and IgG against Aggregatibacter actinomycetemcomitans in 109 periodontitis participants with various BMIs were measured. BMI ≥23.0 kg/m(2) was considered overweight or obese. RESULTS: Plasma adiponectin was decreased (P = 0.04), whereas CRP and IgG against P. gingivalis were increased (P = 0.04 and P = 0.001, respectively) in patients with severe periodontitis compared with patients with mild or moderate periodontitis, independent of overweight or obese status. Plasma CRP, ICAM-1, and leptin were increased (P <0.001, P = 0.007, and P <0.001, respectively) and adiponectin was decreased (P = 0.04) in overweight or obese participants compared with normal weight participants, without influence of periodontitis severity. No interaction effect between periodontitis and overweight or obese status existed for these protein levels after the data were adjusted for age, sex, plasma levels of triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure (P = 0.48). CONCLUSIONS: Periodontitis and overweight or obese BMI change plasma levels of the inflammatory mediators adiponectin and CRP, independently. This study suggests a role of periodontitis in systemic inflammatory response in Thai people who are overweight or obese.

Direct Immunofluorescence in Oral Lichen Planus.

INTRODUCTION: Oral lichen planus (OLP) is a common immune-mediated oral mucosal disease. Diagnosis of OLP depends mainly on both clinical and histopathological features. Direct immunofluorescence (DIF) is a useful investigation method to distinguish between similar lesions and to confirm diagnosis in cases of uncharacterized features. AIM: The purpose of this study was to evaluate the prevalence and pattern of DIF in a group of Thai patients with OLP. MATERIALS AND METHODS: Records of clinically and histologically diagnosed OLP patients attending the Oral Medicine Clinic, Faculty of Dentistry, Mahidol University, Bangkok, Thailand were consecutively reviewed for DIF results. The DIF patterns in these patients were analysed. RESULTS: There were 82 atrophic and/or erosive OLP patients with a mean age of 51.6 years. Male to female ratio was 1:5. Of these, 82.9% showed positive DIF. Buccal mucosa was superior to the gingiva and palate in terms of sensitivity for DIF. All specimens except one (98.5%) demonstrated deposition of fibrinogen at the basement membrane zone (BMZ) in a shaggy pattern. The most common DIF pattern was shaggy fibrinogen at BMZ with IgM deposition on the colloid bodies (CB) (35.3%) followed by shaggy fibrinogen along BMZ (27.9%). CONCLUSION: The prevalence of positive DIF in Thai OLP patients was 82.9%. The most common finding was shaggy fibrinogen at BMZ. The typical pattern was shaggy fibrinogen along BMZ with or without positive IgM at CB. DIF pattern could be evaluated for the diagnosis of OLP lacking clinical and/or histopathological characteristic features.

Association of untreated metabolic syndrome with moderate to severe periodontitis in Thai population.

BACKGROUND: Metabolic syndrome (MetS) correlates with systemic inflammation. A relation of MetS to periodontitis has been reported. This study aims to evaluate whether periodontitis is associated with untreated MetS, plasma adiponectin, and leptin among Thai people. METHODS: One hundred twenty-five participants (aged 35 to 76 years) were recruited. Demographic and biologic data, bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) of all teeth were examined. Plasma adiponectin and leptin levels were measured. RESULTS: Forty-four participants (35.2%) were healthy, and 81 (64.8%) had MetS. All periodontal conditions (BOP, PD, and CAL) were significantly worse in patients with MetS than healthy participants. After adjustment for confounders, MetS was strongly associated with severe periodontitis (odds ratio [OR] = 3.60, 95% confidence interval [CI]: 1.34 to 9.65). MetS with four to five components had a higher association with periodontitis than did MetS with three components (OR = 5.49, 95% CI: 1.75 to 17.19), whereas each separate component had no association with periodontitis, except for high diastolic blood pressure. Periodontitis was also associated with age (OR = 1.08, 95% CI: 1.01 to 1.14) and education (OR = 3.76, 95% CI: 1.05 to 13.40). The risk of MetS was predicted by body mass index and plasma adiponectin (OR = 1.90, 95% CI: 1.24 to 2.92 and OR = 0.93, 95% CI: 0.88 to 0.98, respectively). CONCLUSIONS: There may be a relationship between untreated MetS and periodontitis in Thai people. Periodontal diagnosis should be regularly conducted in patients with MetS.

Comparison of salivary and plasma adiponectin and leptin in patients with metabolic syndrome.

BACKGROUND: The relationship of saliva with plasma protein levels makes saliva an attractive diagnostic tool. Plasma levels of adiponectin and leptin in healthy individuals or diabetes mellitus patients have been previously reported. Nevertheless, salivary levels of these adipocytokines in patients with metabolic syndrome (MS) have never been investigated. This study was aimed to determine adiponectin and leptin levels in saliva and plasma from patients with metabolic syndrome, and evaluate any correlation of these levels with MS. METHODS: Forty-six healthy and 82 MS patients were enrolled. Demographic data and blood biochemistries were recorded. Saliva and plasma adiponectin and leptin levels were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Adiponectin and leptin were higher in plasma than in saliva (p < .001). Plasma adiponectin was decreased and plasma leptin increased in patients with MS (p < .001). Salivary adiponectin and salivary leptin were not different between healthy subjects and MS patients (p = .619 and p = .523). Correlation between salivary and plasma adiponectin showed significant association (r = .211, p = .018) while salivary and plasma leptin had no correlation (r = -.161, p = .069). Significant correlation was observed between the salivary adiponectin/salivary leptin ratio and plasma adiponectin (r = .371, p < .001), but not with any component of MS. Increased triglyceride and waist circumference were associated with risk of having a low level of plasma adiponectin (OR = 1.009; 95% CI 1.002-1.015 and OR = 1.125; 95% CI 1.029-1.230). For leptin, body mass index and high-density lipoprotein cholesterol (HDL-C) were associated with a high level of plasma leptin (OR = 1.621; 95% CI 1.212-2.168 and OR = .966; 95% CI .938-.996). The OR for MS as predicted by plasma adiponectin was .928 (95% CI .881-.977). CONCLUSIONS: This study showed that salivary adiponectin and leptin do not correlate with MS. Although correlation between salivary and plasma adiponectin was observed, no association with MS was observed. Only plasma adiponectin may be useful for the prediction of MS.

The prevalence of carotid artery calcifications detected on panoramic radiographs in patients with metabolic syndrome.

OBJECTIVES: The purpose of this study was to determine the prevalence of carotid artery calcifications (CAC) detected on panoramic radiographs in patients with metabolic syndrome (MetS). STUDY DESIGN: Eighty-five Thai subjects (29 men, 56 women) who had MetS according to the International Diabetes Federation definition were evaluated for CAC detected on panoramic radiographs. The confirmation of findings was done by ultrasonography. RESULTS: Carotid artery calcifications were detected in 19 subjects (22.4%) with a mean age of 64 years, range 48-74 years. These subjects included 12 men and 7 women. The CAC were significantly more common in men than in women (P = .002). There were 8 subjects (9.4%) with bilateral calcifications and 11 subjects (12.9%) with unilateral calcification. No significant difference between the right and left sides was found (P = .44). CONCLUSION: Thai people with MetS have high prevalence of radiographically detectable carotid artery calcifications.

Carotid artery calcification detected on panoramic radiographs in a group of Thai population.

OBJECTIVE: To determine the prevalence of carotid artery calcification (CAC) detected on panoramic radiographs in a Thai population. STUDY DESIGN: The panoramic radiographs of the patients 50 and older (N = 1,370) visiting Mahidol University from January 1998 through September 2004 were retrospectively reviewed for CAC. The medical records of the positive subjects were then reviewed. RESULTS: Thirty-four (2.5%) of the 1,370 patients, 16 men and 18 women, with a mean age of 69 and a range of 50 to 87 years, had 1 or more CACs. These calcifications were unilateral in 25 (73.5%) and bilateral in 9 (26.5%) subjects. Of those positive subjects, 18 reported hypertension, 10 reported diabetes mellitus, and 5 reported hyperlipidemia. CONCLUSIONS: Although it is uncommon to find CAC in the Thai population, dentists should be aware of this calcification on the routine panoramic radiographs and promptly refer for cerebrovascular and cardiovascular evaluation.