Hypertension and non insulin-dependent diabetes mellitus (NIDDM) are well-known risk factors for atherosclerotic disease. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion ...molecule-1 (VCAM-1) may exert a relevant role in the pathogenesis of atherosclerosis; their prognostic relevance has been recently demonstrated. The aim of the study was to investigate possible inter-relation between circulating adhesion molecule levels, carotid artery structure and endothelial function in 15 patients with NIDDM, as well as in 15 patients with both NIDDM and essential hypertension (NIDDM+EH) compared with 15 normal subjects (NS) and 15 euglycaemic patients with EH, matched for age, sex and body weight. All subjects were submitted to a biopsy of the gluteal subcutaneous fat. Small arteries were dissected and mounted on a micromyograph, and the media-to-lumen (M/L) ratio was then calculated. Carotid artery structure was investigated by Doppler ultrasound. Endothelial function was evaluated by investigation of the flow-mediated dilatation (FMD) of the brachial artery. ICAM-1 and VCAM-1 plasma levels were measured by ELISA. ICAM-1 and VCAM-1 plasma levels were significantly greater and FMD smaller in EH, NIDDM and NIDDM+EH than in NS, but no difference was observed among the three pathological groups. Carotid artery structural changes were more pronounced in NIDDM+EH. No significant difference was observed among NIDDM, EH and NS. The M/L ratio of subcutaneous small resistance arteries was significantly greater in NIDDM+EH than in NIDDM or EH. NS had a smaller M/L ratio than the other groups. Significant correlations were observed between ICAM-1 plasma levels and indices of carotid artery structure in diabetic patients. However, the relations were close only in NIDDM+EH. In conclusion, our data suggest that NIDDM+EH may present more pronounced vascular structural alterations than NIDDM, and that adhesion molecules plasma levels are closely inter-related with carotid artery structural alterations, at least in NIDDM+EH, but not with M/L ratio of small resistance arteries.
OBJECTIVEThe time course of programmed cell death (apoptosis) in the vasculature of spontaneously hypertensive rats (SHRs) is still unclear. Moreover, no data are presently available about the ...possible interrelationships between apoptosis and vascular remodelling. The aim of this study was to investigate the mesenteric small resistance arteries and large arteries (aortas) of SHRs and normotensive Wistar-Kyoto (WKY) rats at different ages, before and after the development of overt hypertension.
METHODSTwenty-four SHRs (4, 8 or 12 weeks old) and 24 age-matched WKY rats were included in the study. Blood pressure was measured non-invasively. Rats were killed by decapitation and segments of aortas and small mesenteric arteries were dissected free from the surrounding tissue. Mesenteric arteries were mounted on a micromyograph and structural characteristics were measured (media thickness, media:lumen ratio, etc.). Apoptotic cells in the tunica media of large and small vessels were then stained using modified TdT-mediated dUTP Nick-End Labeling (TUNEL).
RESULTSAt 4 weeks of age no difference in the blood pressure and percentage of apoptosis in mesenteric arteries between SHRs and WKY rats was detected; however, the medialumen ratio of mesenteric small resistance arteries was significantly greater in SHRs. At 8 and 12 weeks of age systolic blood pressure, medialumen ratio and apoptosis rate in mesenteric small arteries was significantly higher in SHRs. The rate of apoptosis in the aortas was similar in the two strains at all three ages.
CONCLUSIONSAn increased prevalence of apoptosis was observed in mesenteric small arteries of 8- and 12-week-old SHRs. It is possible that apoptosis may exert a role in small resistance artery remodelling during the development and establishment of hypertension.
Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data ...are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker, candesartan cilexetil, on indices of subcutaneous small resistance artery structure in 15 patients with mild hypertension and NIDDM. Eight patients were treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from the gluteal region at baseline and after 1 year of treatment. Small arteries were dissected and mounted on a micromyograph and the media-to-internal lumen ratio was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was assessed. A similar blood pressure-lowering effect and a similar reduction of the media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular collagen content was reduced and metalloproteinase-9 was increased by candesartan, but not by enalapril. Changes of circulating indices of collagen turnover and circulating matrix metalloproteinase paralleled those of vascular collagen. The 2 drugs equally improved endothelial function. In conclusion, antihypertensive treatment with drugs that inhibit the renin-angiotensin-aldosterone system activity is able to correct, at least in part, alterations in small resistance artery structure in hypertensive patients with NIDDM. Candesartan may be more effective than enalapril in reducing collagen content in the vasculature.
BACKGROUND:Despite hyperaldosteronism being suggested as predisposing to arrhythmias, the relationship between atrial fibrillation and primary aldosteronism remains uncertain. Therefore, we tested ...the hypothesis that atrial fibrillation is a presentation of primary aldosteronism in hypertensive patients with unexplained atrial fibrillation.
DESIGN AND METHODS:The Prospective Appraisal on the Prevalence of Primary Aldosteronism in Hypertensive (PAPPHY) Study recruited consecutive patients with atrial fibrillation and an unambiguous diagnosis of arterial hypertension at three referral centers for hypertension.
RESULTS:In a cohort entailing 411 atrial fibrillation patients, we identified 18% (age 61 ± 11 years; 32% women), who showed no known cause of the arrhythmia. A thorough diagnostic work-up allowed us to identify primary aldosteronism in 73 of these patients, i.e. 42% 95% confidence interval (CI) 31.8–53.9. Subtyping of primary aldosteronism demonstrated that surgically curable forms of primary aldosteronism accounted for 48% of the cases (95% CI 31.9–65.2). The high prevalence of primary aldosteronism was confirmed at sensitivity analyses.
CONCLUSION:These results provided compelling evidence that primary aldosteronism is highly prevalent in hypertensive patients with unexplained atrial fibrillation. Accordingly, they suggest that patients with no identifiable cause of the arrhythmia should be screened for primary aldosteronism to identify those who can be cured or markedly improved with target treatment.
CLINICAL TRIAL REGISTRATION:https://clinicaltrials.gov, IdentifierNCT01267747.
BACKGROUNDArterial hypertension is frequently associated with the presence of structural alterations in small arteries. Moreover, a reduced coronary flow reserve and vasodilator capacity has been ...observed in essential hypertensive patients, possibly due, at least in part, to microangiopathy of small coronary vessels. The aim of the present study was to evaluate a possible relationship between subcutaneous small artery structure and coronary flow reserve or vasodilator capacity in patients with essential hypertension.
METHODS AND RESULTSA total of 20 patients with mild to moderate essential hypertension were included in the study, and underwent a biopsy of the subcutaneous fat from the gluteal region. Small arteries were dissected and mounted on a micromyograph. The media thickness, the normalized internal diameter and the media lumen ratio (M/L) were then calculated. In addition, a transesophageal Doppler echocardiographic study, which allows the measurement of coronary flow velocity before and during maximal pharmacological vasodilatation, was performed. Coronary flow reserve (CFR) was measured as the ratio of coronary flow velocity assessed during adenosine infusion and that measured in basal conditions. From blood pressure and coronary flow velocity during adenosine infusion, minimum coronary resistance was calculated. CFR as well as minimum coronary resistance were significantly correlated to both M/L and to normalized internal diameter of subcutaneous small arteries.
CONCLUSIONSOur results are consistent with the hypothesis of a generalized remodelling of small arteries in the body, including the coronary circulation; this remodelling may play an important role in the reduction of coronary vasodilator capacity in patients with mild to moderate essential hypertension.
Resection for perihilar cholangiocarcinoma (pCCA) in primary sclerosing cholangitis (PSC) has been reported to lead to worse outcomes than resection for non-PSC pCCA. The aim of this study was to ...compare prognostic factors and outcomes after resection in patients with PSC-associated pCCA and non-PSC pCCA.
The international retrospective cohort comprised patients resected for pCCA from 21 centres (2000–2020). Patients operated with hepatobiliary resection, with pCCA verified by histology and with data on PSC status, were included. The primary outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications.
Of 1128 pCCA patients, 34 (3.0%) had underlying PSC. Median overall survival after resection was 33 months for PSC patients and 29 months for non-PSC patients (p = .630). Complications (Clavien-Dindo grade ≥ 3) were more frequent in PSC pCCA (71% versus 44%, p = .003). The rate of posthepatectomy liver failure (21% versus 17%, p = .530) and 90-day mortality (12% versus 13%, p = 1.000) was similar for PSC and non-PSC patients.
Median overall survival after resection for pCCA was similar in patients with underlying PSC and non-PSC patients. Complications were more frequent after resection for PSC-associated pCCA, with no difference in postoperative mortality.
Objective
Wall-to-lumen ratio of retinal arterioles might serve as an in-vivo parameter of vascular damage. Previous studies have shown a correlation between retinal arteriolar structure and blood ...pressure values, measured both in the clinic and during 24 hours ambulatory monitoring. We analyzed the impact of brachial clinic blood pressure (BP), of central BP and of 24 hours BP values on wall-to-lumen ratio of retinal arterioles.
Methods
In 267 subjects (129 males, age range 20–72 years; mean 54±7 years) wall-to-lumen ratio of retinal arterioles was assessed in vivo using scanning laser doppler flowmetry (Heidelberg retina flowmeter, Heidelberg Engineering). In addition clinic and 24 hours BP values were measured. Central hemodynamics and augmentation index (Ai) were assessed by pulse wave analysis.
Results
In never treated patients with essential hypertension (n=56) a higher wall-to-lumen ratio (0.37±0.19 vs. 0.30±0.13, P=0.05) was observed in comparison with normotensive individuals (n=115); no significant differences were observed between treated (n=96) and untreated hypertensive patients.
Wall to lumen ratio and wall cross sectional area of retinal arterioles were significantly related to clinic systolic BP(r=0.23, P=0.005) and PP(r=0.18, P=0.005), to 24 hours systolic BP(r=0.28, P=0.0001) and PP(r=0.19, P=0.003) and to central systolic BP(r=0.20, P=0.01) and central PP(r=0.21, P=0.001). Multiple regression analysis including all BP indices revealed that only mean systolic 24 hours BP is independently associated with an increased wall-to-lumen ratio of retinal arterioles.
Conclusion
in this quite large group of hypertensive patients and normotensive individuals 24 hours systolic BP seems to be the strongest determinant of increased WLR of retinal arterioles.
Background
Carotid-femoral pulse wave velocity (cfPWV) is an independent predictor of cardiovascular events and its measurement is recommended by current hypertension guidelines. Few data are ...available on the progression of PWV over time. The aim of the present study was to assess the progression of aortic stiffness over a 5-year period in a general population in Northern Italy (Vobarno Study).
Methods
227 subjects, 42% males(age 50±4 years, hypertension in 51% at baseline visit, BL), underwent a BL and a follow up (FU) visit, after 5.1±0.4 years. In all subjects laboratory examinations, measurement of clinic and 24 hours blood pressure(BP) and of cfPWV were performed at BL and at FU.
Results
In the overall population cfPWV increased from 8.28±1.27 at BL to 8.51±3.2 m/s at FU(p<0.05), change: 0.22±1.25. cfPWV significantly increased from BL to FU in hypertensive subjects (HT)(from 8.61 ±1.41 to 8.90±1.40, p<0.01)but not in normotensives (NT)(from 7.97±1.03 to 8.11±1.11, p n.s). The absolute change in cfPWV from BL to FU progressively increased from -0.052±0.108 in NT, to 0.480±0.163 in treated HT and to 0.483±0.138 in untreated HT(p for trend<0.01);after adjustment for possible confounders(age, gender, BMI, baseline cfPWV and change in mean BP)the difference remained statistically significant. At multivariate analysis the variables independently related to the progression of cfPWV were cfPWV and mean BP at BL (beta −0.55, p<0.01, and beta 0.18, p<0.01, respectively) and the change in mean BP during follow-up (beta 0.20, p = 0.001).
Conclusions
In a general population sample in Northern Italy the main determinants of the increase in arterial stiffness during a 5 years FU were cfPWV and mean BP at BL and change in mean BP over time.
Background
The determinants of aortic stiffness have been elucidated in several studies, while few data are available for carotid stiffness. Aim of the study was to identify the main determinants of ...carotid arterial stiffness parameters in a general population in Northern-Italy(Vobarno Study).
Methods
183subjects(61% female, mean age 55± 4,53% hypertensives,59% treated) underwent laboratory examinations and both clinic and 24 hours BP measurement (Spacelabs 90207). A non-invasive echotracking system was used to measure intima-media thickness, diameter, distension, distensibility (Dist), distensibility coefficient (CDist), compliance coefficient (CC) and elastic modulus (Einc) on 4-cm long common carotid artery segment. Results: correlation coefficient of Dist, CDist and Einc are shown in Table 1.
At multivariate analysis the independent predictor of Dist, CDist and Einc were age (β = -0.22, β = -0.22 and β = 0.18, respectively, all p<0.01), BMI (β = -0.18, β = -0.18 and β = 0.14, respectively, all p<0.05), MBP (β = -0.34, β = -0.33 and β = 0.40, respectively, all p<0.001)and female gender(β = 0.19, β = 0.18 and β = -0.15, respectively, all p<0.05). When carotid arterial stiffness parameters were compared in males and females, a significantly lower values of Dist and CC were observed in females (365±97 vs 427±124 μm, p<0.001 and 0.63±0.24 vs 0.83±0.29 mm
2
/kPa
−1
, p<0.001, respectively). After adjusting for possible confounders in a multivariate model distension(345 vs 456 μm, p<0.001), CDist (23.4 vs 30.3 kPa
−1
*10
−3
, p<0.001) and CC (0.61 vs0.87 mm
2
/kPa
−1
, p<0.001)were significantly lower in females while Einc was significantly higher in females(0.45 vs 0.34 kPa*10
3
, p = 0.007). Conclusion: in a general population sample age, female gender, BMI and clinic and 24 hours BP values are associated to an increase local carotid stiffness.
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