(Hypertension. 1999;34:655-658.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Rarefaction of Skin Capillaries in Borderline Essential Hypertension Suggests an Early Structural Abnormality
From the Blood Pressure Unit (T.F.T.A., N.D.M., G.A.M.), Dermatology Unit, Department of Medicine (P.S.M.), and the Clinical Pharmacology Unit, Department of Pharmacology and Clinical Pharmacology (T.F.T.A., D.R.J.S.), St. George's Hospital Medical School, London, U.K.
Correspondence to Dr Tarek F.T. Antonios, Clinical Pharmacology Unit, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, U.K. E-mail t.antonios{at}sghms.ac.uk
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Abstract |
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Abstract—We recently showed that rarefaction of skin capillaries in the dorsum of the fingers of patients with essential hypertension is due to the structural (anatomic) absence of capillaries rather than functional nonperfusion. It is not known whether this rarefaction is primary (ie, antedates the onset of hypertension) or secondary (ie, as a consequence of sustained and prolonged elevation of blood pressure [BP]). The aim of the present investigation was to study skin capillary density in a group of patients with mild borderline hypertension to assess whether rarefaction antedates the onset of sustained elevation of BP. The study group included 18 patients with mild borderline hypertension (mean supine BP, 136/83 mm Hg), 32 normotensive controls (mean BP, 126/77 mm Hg), and 45 patients with established essential hypertension (mean BP, 156/98 mm Hg). The skin of the dorsum of the fingers was examined by intravital capillary videomicroscopy before and after venous congestion at 60 mm Hg for 2 minutes. Patients with borderline essential hypertension had the lowest resting capillary density when compared with normotensive controls and patients with established hypertension. Maximal capillary density with venous congestion in the borderline group remained the lowest. The study confirmed that patients with borderline essential hypertension have skin capillary densities that are equally low as or even lower than patients with established hypertension. Both groups had significantly lower capillary densities than normal controls. One explanation for the results is that capillary rarefaction may be due to an early structural abnormality in essential hypertension.
Key Words: hypertension, essential • microcirculation • capillaries • blood vessels, rarefaction
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Introduction |
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Rarefaction of capillaries and arterioles is now a well-established abnormality that occurs in many tissues in patients with human essential hypertension.1 2 3 4 5 We recently showed that the rarefaction of capillaries in the skin of the dorsum of the fingers in patients with essential hypertension is due to the structural (anatomic) absence of capillaries rather than nonperfusion or functional rarefaction.1 It is not yet known whether this rarefaction is primary (ie, antedates the onset of hypertension) or secondary (ie, occurring as a consequence of prolonged elevation of blood pressure). Previous studies indicated that rarefaction may occur in patients with borderline essential hypertension and only intermittent elevations of blood pressure.6 The use of the term "borderline hypertension" has been most confusing. According to the 1999 World Health Organization–International Society of Hypertension (WHO-ISH) guidelines for the management of hypertension,7 which are based on the sixth report of the United States' Joint National Committee (JNC-VI),8 the definition of borderline mild hypertension is a systolic blood pressure (SBP) between 140 and 149 mm Hg and a diastolic blood pressure (DBP) between 90 and 94 mm Hg. A more physiologically oriented definition of borderline hypertension is a state in which blood pressures have been documented within the normal range (ie, <140/90 mm Hg), but on at least 2 occasions, they have been documented as above that level.9 The aim of this study was to assess whether rarefaction of skin capillaries in patients with essential hypertension is an early abnormality that antedates the onset of the sustained elevation of blood pressure or if it is a secondary phenomenon that occurs as a consequence of the raised blood pressure.
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Methods |
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Subjects
Subjects consisted of 18 patients with mild borderline essential hypertension (whose blood pressures have been documented within the normal range [<140/90 mm Hg] but on at least 2 occasions were above that level but <150/95 mm Hg), 45 patients with previously untreated, established essential hypertension (SBP>160 mm Hg and/or DBP>95 mm Hg), and 32 normotensive controls (SBP<140 mm Hg and DBP<85 mm Hg on repeated measurements). All patients were assessed in the Blood Pressure Unit of St George's Hospital Medical School, and they were included in the study if no underlying cause for their high blood pressure was found. Patients with a history of connective tissue disease, diabetes mellitus, or skin diseases or who were on vasoactive drugs were excluded from the study. The protocol was approved by the local Ethics Committee of St. George's Hospital. Written informed consent was obtained from each patient.
Intravital Capillaroscopy
All capillaroscopy studies were done in parallel. Subjects were
studied in the morning between 9 and 11 AM after an
overnight fast. The capillaroscopy studies were performed in a
temperature-controlled laboratory (21°C to 24°C) after the study
subjects had rested for at least 20 minutes in the semisupine position.
Room temperature was monitored before and during the studies and, if
necessary, the temperature was adjusted by the use of fan heaters or
air conditioning. Patients were seated with the left forearm and hand
supported at the heart level. Both the hand and the forearm rested on a
splint surrounded by a vacuum pillow (a specially constructed pillow
filled with polyurethane foam that can be molded to any desired shape
by creating a vacuum) to restrict movement. Videomicroscopy with an
epi-illuminated microscope containing a 100-W mercury vapor lamp light
source, a PL 6.3/0.2 objective (Wild-Leitz type 307 to 143.004,
Leica UK Ltd), and a final magnification of x196 was used. Microscopic
images were recorded with a charge-coupled device camera
(Hitachi; model, CCD HV-725K) and transferred with a videoscaler
(VS-1000) and videotimer (For-A VTG 33) for storage onto a video
recorder (Panasonic; model, AUC 7350).
The skin of the dorsum of the middle phalanx of the nondominant (usually, left) hand was examined. Four microscopic fields (0.68 mm2 each) centered around an ink spot were recorded continuously for 5 minutes to detect intermittently perfused capillaries. Still-frame video prints (Sony Multiscan Video-Printer UP-930) obtained from each recorded field were analyzed offline. The number of capillaries per field was counted by hand from these prints and from live playback of the recorded tapes. Skin temperature was monitored throughout the study with a temperature probe on the dorsum of the left index finger (YSI Telethermometers). Patients with cold hands or with Raynaud's phenomenon were excluded from the study.
Maximization of Visualized Skin Capillaries
The enhancing effect of venous congestion on the visualization
of skin capillaries by videomicroscopy was previously
reported.10 We recently showed that venous congestion
maximizes the number of visible capillaries1 more than
reactive hyperemia; it does this by increasing their red cell
content. In this study, a miniature blood pressure cuff was applied to
the base of the left middle finger and the cuff was then inflated and
maintained at 60 mm Hg for 2 minutes; further images were
recorded with the use of 1 of the 4 microscopic fields chosen at
random.
Blood Pressure and Heart Rate
Blood pressure was measured with a semiautomatic ultrasound
sphygmomanometer (ArterioSonde, Roche) with an appropriate cuff size.
Supine and standing BP were taken as the mean of 3 readings obtained at
1- to 2-minute intervals with the patient in the corresponding
position.
Blood Analysis
Venous blood was taken without stasis after the patient had been
sitting upright for 10 minutes. Variables measured included serum
electrolytes, urea, creatinine, uric acid, glucose, total
cholesterol, triglycerides, and full blood
count.
Statistical Analysis
All results are given as means±SEM. The data were
processed by StatView 5.0 (SAS Institute Inc). ANOVA and Bonferroni's
post hoc tests were used to compare groups. P<0.05 was
considered statistically significant.
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Results |
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The Table shows baseline characteristics and capillaroscopic data in the study subjects before and after 2 minutes of venous congestion at 60 mm Hg. A significant reduction (30%) occurred in mean capillary density at baseline (before venous congestion) in the borderline and established hypertensive subjects compared with the normotensive controls (57±4 and 58±3 compared with 76±3 per 0.68 mm2, respectively; P<0.0001) (Figure). With venous occlusion, capillary density increased significantly in both hypertensive groups (36% in the borderline group and 30% in the established hyper- tensive subjects); however, maximal capillary density was significantly lower in both groups as compared to normo- tensive controls (63±5, 70±3, and 93±3/field, respectively; P<0.0001) (Figure).
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Discussion |
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The present study found that significant structural rarefaction of the skin capillaries occurs in the early stages of human essential hypertension, with only mild intermittent elevation of blood pressure. Therefore, capillary rarefaction may be a primary or very early structural abnormality rather than a consequence of sustained hypertension. The results of this study agree with several previous studies on structural abnormalities in patients with borderline essential hypertension. Sullivan et al6 described the rarefaction of conjunctival capillaries in patients with intermittent elevation of blood pressure. They found that capillary density was inversely related to the cardiac index but not to blood pressure. Some authors consider this rarefaction a form of autoregulation, reflecting the long-term adaptation of microcirculation to the elevated blood pressure or the initial increase of blood flow.11
Our study also agreed with the results of Noon et al,12 who found that people with high blood pressure whose parents also had high blood pressure had fewer capillaries on the dorsum of their fingers, suggesting that defective angiogenesis may be an etiological component in the inheritance of high blood pressure.12 Also, Draaijer et al13 found that sodium-resistant borderline hypertensives had a possible structural reduction in nailfold skin capillary density when compared with both sodium-sensitive and control subjects.
In the Tecumseh blood pressure study, Julius et al14 found that subjects with borderline hypertension had elevated minimal forearm vascular resistance (measured during maximal dilatation), indicating a structural decrease in the cross-sectional area of the vascular bed (rarefaction), and a decreased peak Doppler E/A ratio on echocardiography (evidence of diastolic dysfunction).
A number of studies demonstrated that an elevated cardiac output frequently occurs in patients with borderline hypertension15 16 17 and, as the cardiac output returns to normal levels, a state of sustained DBP elevation is demonstrable.18 19 In actuality, patients with borderline hypertension may have elevated, normal, or reduced cardiac output, and with advancing age, the cardiac output declines in these patients.20 Recently, a number of studies showed that individuals with borderline hypertension, even in the adolescent age range, may have a relative enlargement of the left ventricle as compared with normotensive patients.21 Primary structural rarefaction of capillaries may support the theory of reduced angiogenesis and diminished microvascular growth in primary hypertension.
In conclusion, the study demonstrates significantly low skin capillary densities in patients with mild intermittent borderline essential hypertension, equivalent to the densities in patients with established hypertension. This suggests that rarefaction may be an early event in the development of hypertension and not secondary to the sustained elevation of blood pressure. The study also strongly suggests that much of the reduction in capillary density in hypertension is due to the anatomic absence of capillaries, rather than a functional reduction.
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Footnotes |
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T.F.T.A. designed the study, recruited subjects, collected and analyzed the data, and wrote the article. D.R.J.S. helped write the article. N.D.M. helped recruit subjects and take measurements. P.S.M. and G.A.M. were responsible for overall supervision and also helped write the article.
Received March 18, 1999; first decision March 25, 1999; accepted May 24, 1999.
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References |
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1. Antonios TFT, Singer DRJ, Markandu ND, Mortimer PS, MacGregor GA. Structural skin capillary rarefaction in essential hypertension. Hypertension. 1999;33:998–1001.
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