Tarek F.T. Antonios

Rarefaction of Skin Capillaries in Borderline Essential Hypertension Suggests an Early Structural Abnormality

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.

Structural Skin Capillary Rarefaction in Essential Hypertension

A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension. This rarefaction may play a role in increasing peripheral resistance. However, the mechanism underlying this capillary rarefaction is not understood. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of dorsum of fingers in essential hypertension. The capillary microcirculation was examined with video microscopy before and after maximizing the number of perfused capillaries by venous congestion. The study group comprised 17 patients with essential hypertension (mean supine blood pressure, 155/96 mm Hg) and 17 closely matched normotensive controls (mean blood pressure, 127/77 mm Hg). We used intravital video microscopy with an epi-illuminated microscope to examine the skin of the dorsum of left middle phalanx before and after venous congestion at 60 mm Hg for 2 minutes. A significantly lower mean capillary density occurred at baseline in hypertensive subjects versus normotensive subjects. With venous occlusion, capillary density increased significantly in both groups; however, maximal capillary density remained significantly lower in the hypertensive subjects than in the normotensive subjects. The study strongly suggests that much of the reduction in capillary density in the hypertensive subjects is caused by structural (anatomic) absence of capillaries rather than functional nonperfusion.

Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension

Background: Rarefaction of skin capillaries in people with intermittent borderline essential hypertension suggests a primary or an early abnormality that may antedate the onset of sustained hypertension. Objective: To compare skin capillary density in subjects with and without a family history of essential hypertension. Subjects: 21 normotensive individuals, one or both of whose parents had essential hypertension (mean age 39.3 years; blood pressure 124/79 mm Hg); 21 normotensive controls with no family history of hypertension (age 46.3 years; blood pressure 124/78 mm Hg). Methods: The skin of the dorsum of the fingers was examined by intravital capillary microscopy before and after venous congestion at 60 mm Hg for two minutes. Results: By analysis of variance, both baseline and maximum skin capillary density were lower in subjects with a family history of essential hypertension than in those with no family history (baseline: 67 v 79 capillaries per field, p = 0.008; maximum: 74 v 93 capillaries per field, p < 0.0005). Conclusions: Capillary rarefaction in essential hypertension may occur before the increase in blood pressure and could, at least in part, reflect a primary rather than a secondary abnormality.

Salt—more adverse effects

Salt intake has been shown to be the most important determinant of blood pressure differences both between populations and within populations, as well as the main determinant of the rise in blood pressure with increasing age. In spite of this overwhelming evidence, the food industry for commercial reasons has sustained an artificial debate about the importance of salt intake. This has distracted attention from the other serious effects that a high salt intake may have. A high salt intake (a) exacerbates conditions where there is already sodium and water retention; (b) is the rate limiting factor for carcinoma of the stomach; (c) contributes to left ventricular hypertrophy; (d) is likely to hasten deterioration of renal function and renal disease; (e) is an exacerbating factor in asthma; and (f) increasingly is suggested as a major aggravating factor in osteoporosis.

Angiotensin converting enzyme inhibitors in hypertension : potential problems

Aim: To review potential problems associated with the use of angiotensin converting enzyme (ACE) inhibitors in the treatment of patients with hypertension. Physiological problems: ACE inhibitors cause a drop in blood pressure depending on the circulating level of angiotensin II. This may be a problem in patients with severe congestive heart failure, so that it is important to monitor the effect of the ACE inhibitor in this group. Hyperkalaemia can develop in patients with severe renal impairment and potassium plasma levels should be monitored. Renal impairment is another potential problem and in hypertensive patients renal function should be measured before, and a few weeks after, starting treatment. This is especially important when there is any possibility of fibromuscular hyperplasia or atheroscerotic renal artery stenosis. Non-physiological problems: In addition to a cough, which is the most common problem, skin rashes, loss of taste, haematological effects and angioneurotic oedema are also encountered. The incidence of a cough with most ACE inhibitors is 5-10%. Conclusions: Compared to other antihypertensive drugs, ACE inhibitors have the major advantage of being well tolerated by most patients with few side effects.

DELETERIOUS EFFECTS OF SALT INTAKE OTHER THAN EFFECTS ON BLOOD PRESSURE

1. Salt intake is not only known to play an important role in determining blood pressure (BP) but has been shown to have other deleterious effects independent of BP.

Mid-trimester blood pressure drop in normal pregnancy: myth or reality?

Background Current dogma states that there is a mid-trimester fall in blood pressure (BP) in uncomplicated pregnancy. In the early stages of a longitudinal study of microcirculatory changes in pregnancy, we noted an absence of this mid-trimester fall. Method We prospectively studied this phenomenon in all our subsequent recruits. From a total of 326 women, 255 primigravid white women normotensive at booking and after delivery were studied. Serial BP measurements were taken under controlled conditions through to 38 weeks gestation. BP measurements by midwives were extracted from the case notes of 51 women within this cohort and analysed to validate the results. SBP progressively increased from the first trimester through to 38 weeks gestation. Results The increase from baseline at 13 weeks was significant when compared with measurements at 22 weeks [mean difference: 2.8 mmHg; 95% (confidence interval) CI 1.9–3.7], 28 weeks (mean difference: 5.0 mmHg; 95% CI 3.5–6.5) and 36 weeks (mean difference: 7.7 mmHg; 95% CI 6.2–9.1). DBP showed a nonsignificant dip at 22 weeks (mean difference: −0.12 mmHg; 95% CI −0.92 to 0.68), a nonsignificant increase at 28 weeks (mean difference: 2.0 mmHg; 95% CI 0.80–3.2) and a significant increase at 36 weeks (mean difference: 6.0; 95% CI 4.6–7.3). In the validation cohort, the SBP (P = 0.0001) and DBP showed an increasing trend (P = 0.0001). Conclusion BP measured under controlled conditions showed a progressive rise in pregnancy, with no significant mid-trimester drop. The findings were replicated in the routine antenatal clinic measurements.

Effect of Modest Salt Reduction on Skin Capillary Rarefaction in White, Black, and Asian Individuals With Mild Hypertension

Microvascular rarefaction occurs in hypertension. We carried out a 12-week randomized double-blind crossover trial to determine the effect of a modest reduction in salt intake on capillary rarefaction in 71 whites, 69 blacks, and 29 Asians with untreated mildly raised blood pressure. Both basal and maximal (during venous congestion) skin capillary density were measured by capillaroscopy at the dorsum and the side of the fingers. In addition, we used orthogonal polarization spectral imaging to measure skin capillary density at the dorsum of the fingers and the hand web. With a reduction in salt intake from 9.7 to 6.5 g/day, there was an increase in capillary density (capillaries per millimeter squared) from 101±21 to 106±23 (basal) and 108±22 to 115±22 (maximal) at the dorsum, and 101±25 to 107±26 (basal) and 110±26 to 116±26 (maximal) at the side of the fingers (P<0.001 for all). Orthogonal polarization spectral imaging also showed a significant increase in capillary density both at the dorsum of the fingers and the web. Subgroup analysis showed that most of the changes were significant in all of the ethnic groups. Furthermore, there was a significant relationship between the change in 24-hour urinary sodium and the change in capillary density at the side of the fingers. These results demonstrate that a modest reduction in salt intake, as currently recommended, improves both functional and structural capillary rarefactions that occur in hypertension, and a larger reduction in salt intake would have a greater effect. The increase in capillary density may possibly carry additional beneficial effects on target organs.

Efficacy of Candesartan Cilexetil Alone or in Combination With Amlodipine and Hydrochlorothiazide in Moderate-to-Severe Hypertension

This multicenter study evaluated the efficacy of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, used alone or in combination with amlodipine or in combination with amlodipine and hydrochlorothiazide in the treatment of patients with moderate-to-severe essential hypertension. After a 2-week, single-blind, placebo run-in period, patients entered a 12-week, open-label, dose-titration period. The candesartan cilexetil dose was increased from 8 to 16 mg once daily; amlodipine (5 mg once daily), hydrochlorothiazide (25 mg once daily), and additional medication were also added sequentially if necessary. Patients then entered a final 4-week, parallel-group, double-blind, randomized, placebo-controlled withdrawal period of candesartan alone. A total of 216 patients were recruited. After a 2-week run-in period on placebo tablets, mean sitting blood pressure (BP) was 175/108 mm Hg. At the end of the 12-week dose-titration/maintenance period, mean sitting BP fell to 141/88 mm Hg. In 67 patients who were randomized to placebo and had their candesartan withdrawn, there was a highly significant increase in mean systolic/diastolic BP (13/6 mm Hg) compared with those patients who continued with candesartan (ANCOVA, P <0.0001). In conclusion, candesartan cilexetil is an effective BP-lowering drug when used alone or in combination with amlodipine or amlodipine plus hydrochlorothiazide in the treatment of moderate-to-severe essential hypertension. The drug was well tolerated throughout the investigation period.

How to detect early left atrial remodelling and dysfunction in mild-to-moderate hypertension.

Background and objectives Early changes in left atrial function in hypertension are difficult to assess quantitatively. Measuring atrial reversal flow into the pulmonary veins and regional left atrial deformation parameters assessed by Tissue Doppler-derived strain/rate (S/SR) imaging could provide quantitative assessment of left atrial deformation. We aimed to quantify changes in left atrial volume and deformation and pulmonary flow reversal (PVREVERS) in hypertension to detect subclinical left atrial dysfunction. Design, setting and patients In 74 hypertensive and 34 age-matched normotensive patients (mean age 49 ± 1.4 vs. 44.2 ± 2.1 years) echo studies were performed, including measurements of LAV during reservoir, conduit and pump phases and standard indices reflecting left ventricular filling. S/SR was measured in the lateral left atrial wall. Total deformation (STOTAL) and the contribution to early (SE-index) and late (SA-index) filling were calculated. Results Hypertensive patients had significantly impaired diastolic function and increased left atrial volume during all phases. Only LAVCONDUIT significantly correlated with both ventricular hypertrophy and parameters of diastolic function. Velocity time integral of PVREVERS correlated with blood pressure and LAVCONDUIT. In hypertensive patients STOTAL was significantly higher (54.9 ± 2.6 vs. 45.5 ± 2.7%, P < 0.03) and SE-index was lower (P < 0.0001). This was compensated for by an increased SA-index (P < 0.0001) and SR during atrial contraction (−4.9 ± 0.2 vs. −2.9 ± 0.3 1/s, P < 0.0001). SA-index correlated significantly with blood pressure (R = 0.4; P < 0.0001) and PVREVERS (R = 0.3; P < 0.001). Conclusion Changes in left atrial function due to hypertensive diastolic impairment are best reflected by LAVCONDUIT expansion. Hypertensive atrial dilatation is related to increase in PVREVERS. Left atrial S/SR offers a clinically valuable approach to detecting subclinical atrial dysfunction.