Cynthia Cheng

Functional Capillary Rarefaction in Mild Blood Pressure Elevation

Capillary rarefaction is described in patients with moderate‐to‐severe hypertension. The study objective was to determine if structural and/or functional capillary rarefaction is detectable and associated with endothelial dysfunction in patients with mild blood pressure elevation (HBP: Systolic blood pressure 130–160 mm Hg). Capillary density was quantified by direct capillaroscopy in 110 nondiabetic black and non‐black subjects. Endothelial function was quantified by plethysmographic measures of flow‐mediated vasodilation. Compared to normotensives (NBP: N = 90), functional capillary rarefaction was detected in HBP (N = 20; p < 0.001). Functional capillary density measures correlated with endothelial function (p < 0.001). Functional, but not structural, capillary rarefaction is detectable and associated with endothelial dysfunction in both black and non‐black individuals with mild blood pressure elevation.

Capillary rarefaction in treated and untreated hypertensive subjects.

This study aimed to determine if capillary rarefaction is detectable and associated with endothelial dysfunction in persons with mild systolic blood pressure (SBP) elevation. Capillary density and endothelial function were quantified for 150 nondiabetic participants, grouped by blood pressure (BP) as normotensive, untreated high BP, and treated high BP. Structural capillary rarefaction measures were not different between the three groups. Functional capillary rarefaction measures were significantly lower in both high BP groups compared to normotensives, and correlated inversely with endothelial function. The study findings indicate that the hypertensive vascular pathologic process is already underway at modest levels of blood pressure elevation.

The Reliability of Patient Self-Reported Blood Pressures

Self‐monitoring of blood pressure actively involves patients in hypertension management. However, the usefulness of self‐monitoring of blood pressure may be limited by inaccurate patient reporting. The study objective was to assess reliability of patient blood pressure reporting over 6 months. Forty‐nine subjects with Joint National Committee stage 1 or 2 hypertension were enrolled. Unaware that the monitors electronically store readings, the subjects were asked to check and record outpatient blood pressures twice weekly. Stored and written readings were compared. On average, patient‐recorded blood pressures were equivalent to stored monitor values 80% or more of the time. Reliability of patient self‐reporting was sustained over the 6‐month study period. Notably, patients did not selectively report lower blood pressure readings. The overall mean self‐reported and stored monitor blood pressures were nearly identical: blood pressure (±SD) 134±16.8/78±11.6 mm Hg and 135±19.6/80±13.3 mm Hg, respectively. The reliability of self‐reporting of blood pressures for many patients supports the potential usefulness of self‐monitoring of blood pressure in hypertension management.

Association of Adipokines with Insulin Resistance, Microvascular Dysfunction, and Endothelial Dysfunction in Healthy Young Adults.

Proinflammatory adipokines (inflammation markers) from visceral adipose tissue may initiate the development of insulin resistance (IR) and endothelial dysfunction (ED). This studys objective was to investigate the association of five inflammation markers (CRP and four adipokines: IL-6, TNFα, PAI-1, and adiponectin) with IR (quantitative insulin resistance check index (QUICKI)), microvascular measures (capillary density and albumin-to-creatinine ratio (ACR)), and endothelial measures (forearm blood flow (FBF) increases from resting baseline to maximal vasodilation). Analyses were conducted via multiple linear regression. The 295 study participants were between 18 and 45 years of age, without diabetes or hypertension. They included 24% African Americans and 21% Asians with average body mass index of 25.4 kg/m2. All five inflammation markers were significantly associated with QUICKI. All but adiponectin were significantly associated with capillary density, but none were associated with ACR. Finally, IL-6 and PAI-1 were significantly associated with FBF increase. We also identified a potential interaction between obesity and IL-6 among normal-weight and overweight participants: IL-6 appeared to be positively associated with QUICKI and capillary density (beneficial effect), but the inverse was true among obese individuals. These study findings suggest that inflammation measures may be potential early markers of cardiovascular risk in young asymptomatic individuals.

Association of Capillary Density and Function Measures With Blood Pressure, Fasting Plasma Glucose, and Insulin Sensitivity

J Clin Hypertens (Greenwich). 2010;12:125–135. ©2009 Wiley Periodicals, Inc.

Alterations in capillary morphology are found in mild blood pressure elevation

Objectives Remodeling of small resistance arteries is an early sign of target organ damage in hypertension. Peripheral capillary morphology abnormalities in hypertension are not well studied. The study objective was to determine whether altered capillary morphology is associated with SBP, DBP, or both in individuals without and with mild blood pressure elevation (SBP = 130–160 mmHg). Another objective was to determine whether capillary morphology is associated with minimum forearm vascular resistance, a measure of altered resistance artery structure. Methods Participants included 115 nonpregnant, nondiabetic individuals 23–55 years of age. A five-component morphology score (distribution, tone, configuration, hypertrophy, and extravasates) was developed to describe fingernail bed capillaries visualized using venous congestion in digital photomicrographs. Multiple linear regression models adjusted for age, sex, race, tobacco use, hyperglycemia, dyslipidemia, and renal function were used to analyze the relationship between SBP, DBP, and minimum forearm vascular resistance with the morphology score. Results The total morphology score was significantly associated with SBP and DBP as well as minimum forearm vascular resistance (P < 0.005 for all). Among the five individual morphology score components, hypertrophy was significantly associated with SBP and DBP (P = 0.002 and 0.001, respectively), whereas extravasates were significantly associated with SBP only (P = 0.002). Conclusion A five-component capillary morphology score is associated with SBP, DBP, and altered resistance artery structure in individuals with and without mild blood pressure elevation. These observations suggest that target organ damage at the level of the microcirculation can be detected using capillary morphology.

A Reproducible Computerized Method for Quantitation of Capillary Density using Nailfold Capillaroscopy

Capillaroscopy is a non-invasive, efficient, relatively inexpensive and easy to learn methodology for directly visualizing the microcirculation. The capillaroscopy technique can provide insight into a patients microvascular health, leading to a variety of potentially valuable dermatologic, ophthalmologic, rheumatologic and cardiovascular clinical applications. In addition, tumor growth may be dependent on angiogenesis, which can be quantitated by measuring microvessel density within the tumor. However, there is currently little to no standardization of techniques, and only one publication to date reports the reliability of a currently available, complex computer based algorithms for quantitating capillaroscopy data.(1) This paper describes a new, simpler, reliable, standardized capillary counting algorithm for quantitating nailfold capillaroscopy data. A simple, reproducible computerized capillaroscopy algorithm such as this would facilitate more widespread use of the technique among researchers and clinicians. Many researchers currently analyze capillaroscopy images by hand, promoting user fatigue and subjectivity of the results. This paper describes a novel, easy-to-use automated image processing algorithm in addition to a reproducible, semi-automated counting algorithm. This algorithm enables analysis of images in minutes while reducing subjectivity; only a minimal amount of training time (in our experience, less than 1 hr) is needed to learn the technique.

Non-invasive assessment of microvascular and endothelial function.

The authors have utilized capillaroscopy and forearm blood flow techniques to investigate the role of microvascular dysfunction in pathogenesis of cardiovascular disease. Capillaroscopy is a non-invasive, relatively inexpensive methodology for directly visualizing the microcirculation. Percent capillary recruitment is assessed by dividing the increase in capillary density induced by postocclusive reactive hyperemia (postocclusive reactive hyperemia capillary density minus baseline capillary density), by the maximal capillary density (observed during passive venous occlusion). Percent perfused capillaries represents the proportion of all capillaries present that are perfused (functionally active), and is calculated by dividing postocclusive reactive hyperemia capillary density by the maximal capillary density. Both percent capillary recruitment and percent perfused capillaries reflect the number of functional capillaries. The forearm blood flow (FBF) technique provides accepted non-invasive measures of endothelial function: The ratio FBF(max)/FBF(base) is computed as an estimate of vasodilation, by dividing the mean of the four FBF(max) values by the mean of the four FBFbase values. Forearm vascular resistance at maximal vasodilation (FVR(max)) is calculated as the mean arterial pressure (MAP) divided by FBF(max). Both the capillaroscopy and forearm techniques are readily acceptable to patients and can be learned quickly. The microvascular and endothelial function measures obtained using the methodologies described in this paper may have future utility in clinical patient cardiovascular risk-reduction strategies. As we have published reports demonstrating that microvascular and endothelial dysfunction are found in initial stages of hypertension including prehypertension, microvascular and endothelial function measures may eventually aid in early identification, risk-stratification and prevention of end-stage vascular pathology, with its potentially fatal consequences.

Validation of the Dietary Risk Assessment Food Frequency Questionnaire against the Keys Score for Saturated Fat and Cholesterol

OBJECTIVE The objective of this pilot study was to validate the Dietary Risk Assessment (DRA) food frequency questionnaire against the Keys score obtained from 2 2-day dietary recalls in a sample of subjects. DESIGN Cross-sectional study design. SETTING Urban university-based family practice. PARTICIPANTS The 105 subjects included outpatients, medical students, and staff. MAIN OUTCOME MEASURE Correlation between the DRA and Keys score. ANALYSIS Pearson correlation analysis. RESULTS We found that the correlation between the DRA and Keys score derived from the dietary recalls was .62 (P < .001). CONCLUSIONS AND IMPLICATIONS The simplicity of the DRA and its correlation with dietary recall may make this a useful dietary analysis and nutrition education tool for both patients and physicians.

Association of ambulatory heart rate and atherosclerosis risk factors with blood pressure in young non-hypertensive adults

Objective The study objective was to assess the association between 24 h ambulatory heart rate (HR), atherosclerosis risk factors and blood pressure (BP) in young non-hypertensive patients. Methods We recruited 186 participants aged 18–45 years from a large urban academic Family Medicine outpatient practice, serving 40 000 individuals for this observational study. The main analyses were based on multiple linear regression, with mean 24 h BP (systolic BP (SBP) or diastolic BP (DBP)) as the outcomes, mean 24 h HR as the main predictor of interest, and controlling for age, gender, race, insulin sensitivity/resistance and endothelial function measured by strain gauge venous occlusion plethysmography. Results HR was independently associated with mean 24 h SBP and DBP (SBP and DBP: p=0.042 and 0.001, respectively). In our analyses, associations were markedly stronger for ambulatory compared with office BP measurements. Endothelial dysfunction was associated with higher SBP (p=0.013); plasminogen activator inhibitor-1 was significantly associated with both SBP and DBP (p=0.041 and 0.015, respectively), while insulin resistance was not associated with either SBP or DBP. Insulin resistance and C reactive protein were significant predictors of HR (p=0.013 and 0.007, respectively). Conclusions These findings suggest that HR may be a potential marker of elevated cardiovascular risk in young asymptomatic individuals, prior to the development of clinical hypertension or cardiovascular disease.