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Biomedical subjects

P Pauletto

Publications and source records attributed to P Pauletto.

At least 19 recordsLinked to original sources

Review article: the metabolic syndrome--a chronic cardiovascular inflammatory condition.

The atherosclerotic process is regulated by inflammatory mechanisms, which also appear to be involved in the modulation of insulin-resistance, a key player in the pathogenesis of the metabolic syndrome (MS). The interaction between components of the clinical phenotype of the MS with its biological phenotype (insulin resistance, dyslipidaemia, etc.) contributes to the development of a pro-inflammatory state characterized by an increased oxidative stress (i.e. oxidized lipoproteins) and a chronic, subclinical vascular inflammation, as also suggested by the increased C reactive protein (CRP) concentration found in patients with MS. The subclinical inflammatory state peculiar of the MS modulates the atherosclerotic process at different stages, resulting in: (i) endothelial dysfunction and increased expression of endothelial adhesion molecules; (ii) an enhanced recruitment of monocytes within the arterial wall, in the early stages of the atherosclerotic process; leading to (iii) the formation of an unstable atherosclerotic plaque, rich in inflammatory cells, which is the culprit lesion in the vast majority of both coronary and cerebrovascular events observed in with MS.

Atherosclerosis↗

Innate immunity and atherogenesis.

Atherosclerosis is recognized as the pathological basis of cardiovascular disease (CVD) and recent advances in basic science have shown that it should be considered as a chronic inflammatory process. Both elements of the innate and the adaptive immunity appear to be actively involved in atherogenesis. In fact, the potential role played by pattern-recognition receptors (Toll-like receptors and scavenger receptors), cytokines (such as IL-1, IL-6, TNFalpha), chemokines and pentraxines (such as CRP and PTX3) represents an emerging field of investigation in atherogenesis. In the near future we expect a better definition of the real biological and clinical impact on CVD of these mediators. On one side, they could become useful to complement traditional risk factors, in order to identify new categories of subjects prone to CVD development. On the other, they could become an additional potential target for therapeutic strategies.

Acute-Phase Proteins↗

Is apoptosis of vascular smooth muscle cells involved in the development of Takayasu arteritis? Suggestions from a case report.

OBJECTIVES: We report a female patient suffering from Takayasu arteritis (TA) who underwent surgical revascularization. METHODS: By studying specimens obtained at surgery, we evaluated the cell composition of the arterial wall, along with the maturation pattern of vascular smooth muscle cells (VSMC) during the active phase of TA. Using TUNEL, we detected apoptotic cells within the tunica media. RESULTS: The highest percentage of apoptotic cells was found in areas where inflammatory infiltrate was present and the medial structure was more or less damaged. Apoptotic cells were also found in structurally preserved areas, where VSMC but not inflammatory cells were present. CONCLUSIONS: Apoptosis involved not only inflammatory cells but also VSMC, particularly those of the immature type. We hypothesize a role for VSMC apoptosis in the development of TA.

Adult↗

Development of a meningioma in a patient with acromegaly during octreotide treatment: are there any causal relationships?

Somatostatin receptors are highly expressed in almost all meningiomas but in this setting their functional role is not clear. A 59-yr-old woman had been treated with octreotide after an unsuccessful operation for a GH-secreting pituitary adenoma. After 8 yr of treatment, a nuclear magnetic resonance (NMR) scan disclosed a 3 cm meningioma of the tentorium. Mean GH was 2.2 ng/ml and IGF-I 325 ng/ml. Meningioma was resected and tissue was digested to obtain tumor cell suspension. Aim of the study was to measure epidermal growth factor (EGF)-induced proliferation of cultured meningioma cells in the presence of either somatostatin or octreotide. Cells were grown to semiconfluency in Dolbecco's modified eagle medium (D-MEM) supplemented with 10% fetal calf serum (FCS). After 48 h in D-MEM without serum, the medium was replaced by fresh medium plus recombinant EGF (10 ng/ml) and somatostatin or octreotide were added in the final concentrations of 1, 10 and 100 nM. 20 h later 1 microcgCi of 3H-thymidine was added to each well. After 4 h, incorporated radioactivity was measured. While octreotide did not influence significantly cell growth at the three dose tested, somatostatin increased thymidine incorporation dose-dependently (peak 100 nM: 150% +/- 27% vs medium plus EGF, p<0.05). Octreotide effectively suppressed GH secretion in our acromegalic patient but is unlikely that its long-term use could have stimulated the growth of meningioma since it did not significantly influence the in vitro proliferation of the meningioma cells. These results suggest that somatostatin-mediated proliferative effect on meningioma cells is not mediated by the subtype 2 of the somatostatin receptor.

Acromegaly↗

In vivo noninvasive identification of cell composition of intimal lesions: a combined approach with ultrasonography and immunocytochemistry.

PURPOSE: We investigated whether differences in cellular composition of the shoulder region of carotid plaque, a cell-rich, debris-free area, can be revealed with computer-driven analysis of ultrasound scans. METHODS: In 26 patients referred for carotid endarterectomy, the shoulder region of plaque eligible for surgical removal was identified with ultrasound scanning. Digital images were obtained and evaluated with a specially developed computer-driven system (Medical Image Processing [MIP]). The gray level distribution of the region of interest (ROI), along with some statistical parameters exploring the spatial distribution of pixels, such as entropy and second angular moment, were analyzed. In the specimen retrieved at surgery, the area corresponding to the ROI was selected. Cryosections were tested at immunocytochemistry with monoclonal antibodies specific to smooth muscle cells (SMCs), macrophages), and lymphocytes. Computerized image analysis was performed to quantify each cellular component of the lesion. RESULTS: Mean gray levels were related positively to the content of SMCs (r = 0.576, P =.002) and negatively to the content of macrophages (r = -0.555, P =.003). Lymphocytes did not show any correlation. Prevalence of SMCs, expressed as the ratio SMC/(SMC + macrophages), was related positively with entropy (r = 0.517, P =.007) and negatively with the second angular moment (r = -0.422, P =.032). The quartiles of gray level were useful for detecting significant differences in terms of cellular composition. CONCLUSIONS: Some cellular features of the shoulder region of plaque are associated with specific videodensitometric patterns evaluated with MIP. This approach enables in vivo noninvasive prediction and monitoring of cell composition of the shoulder region, and could be extended to study of the thickened intima.

Carotid Stenosis↗

Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE). METHODS: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-beta(2)-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed. RESULTS: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT. CONCLUSIONS: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.

Adult↗

Contribution of adventitial fibroblasts to neointima formation and vascular remodeling: from innocent bystander to active participant.

The adventitial layer surrounding the blood vessels has long been exclusively considered a supporting tissue the main function of which is to provide adequate nourishment to the muscle layers of tunica media. Although functionally interconnected, the adventitial and medial layers are structurally interfaced at the external elastic lamina level, clearly distinguishable at the maturational phase of vascular morphogenesis. Over the last few years the "passive" role that the adventitia seemed to play in experimental and spontaneous vascular pathologies involving proliferation, migration, differentiation, and apoptosis of vascular smooth muscle cells (VSMCs) has been questioned. It has been demonstrated that fibroblasts from the adventitia display an important partnership with the resident medial VSMCs in terms of phenotypic conversion, proliferation, apoptotic, and migratory properties the result of which is neointima formation and vascular remodeling. This article is an attempt at reviewing the major themes and more recent findings dealing with the phenotypic conversion process that leads adventitial "passive" (static) fibroblasts to become "activated" (mobile) myofibroblasts. This event shows some facets in common with vascular morphogenesis, ie, the process of recruitment, incorporation, and phenotypic conversion of cells surrounding the primitive endothelial tube in the definitive vessel wall. We hypothesize that during the response to vascular injuries in the adult, "activation" of adventitial fibroblasts is, at least in part, reminiscent of a developmental program that also invests, although with distinct spatiotemporal features, medial VSMCs.

Animals↗

Colorectal cancer metastatic phenotype stimulates production by fibroblasts of N-terminal peptide of type III collagen: clinical implications for prognosis.

In this study we assessed whether the serum levels of the N-terminal peptide of type III collagen (PIIIP), an index of type III collagen synthesis, are influenced by colorectal cancer stage, and whether "in vitro" fibroblast growth and PIIIP production could be altered by tumor tissues obtained from metastatic and nonmetastatic colorectal cancer. 208 colorectal cancer patients (115 colon and 93 rectum) were studied; 54 were stage I, 62 stage II, 37 stage III and 55 stage IV. PIIIP serum levels were significantly higher in stage IV as compared to all other patient groups. The 5-year survival of stage I, stage II, stage III and stage IV patients were 87%, 88%, 32% and 20%, respectively. In the subgroup of stage I and stage II patients considered together, PIIIP (> 0.5 U/ml), but not CEA (> 5 microg/l) serum levels, were predictive for survival. Fibroblast growth was significantly inhibited, while PIIIP production was significantly enhanced, when these cells were conditioned with colorectal cancer homogenates obtained from patients with distant metastases, than from those without distant metastases. In conclusion, colorectal tumors, when metastatic, stimulate fibroblasts' PIIIP synthesis and the serum levels of this peptide might predict patients' outcome after radical surgery.

Carcinoembryonic Antigen↗

Specific cellular features of atheroma associated with development of neointima after carotid endarterectomy: the carotid atherosclerosis and restenosis study.

BACKGROUND: The purpose of this study was to investigate whether some cellular and molecular features of tissue retrieved at carotid endarterectomy are associated with the extent of neointima formation at ultrasound follow-up. METHODS AND RESULTS: One hundred fifty patients were studied. Endarterectomy specimens were tested by immunocytochemistry with the use of (1) monoclonal antibodies that identify smooth muscle cells (SMCs) and fetal-type SMCs on the basis of smooth muscle and nonmuscle myosin content, (2) the anti-macrophage HAM 56, and (3) the anti-lymphocyte CD45RO. The maximum intima-media thickness (M-IMT) of the revascularized vessel was assessed by the use of B-mode ultrasonography 6 months after surgery. The M-IMT values were related positively to the number of SMCs (r=0.534, P<0.0005) and negatively to that of macrophages and lymphocytes (r=-0.428, P<0.0005, and -0.538, P=0.001, respectively). Patients were classified as class 1 (M-IMT </=1.0 mm), class 2 (1. 0 1.3 mm). An abundance of SMCs, mostly of fetal type, was found in the plaque of class 3 patients, whereas lesions from class 1 patients were rich in macrophages and lymphocytes. In the multivariate analysis, factors related to M-IMT were the number of SMCs and the percentage of fetal-type SMCs present in the plaque. CONCLUSIONS: Although the classic risk factors did not play a role, an abundance of SMCs and a scarcity of macrophages characterized the primary lesion of patients in whom neointima developed after surgery. In patients in whom neointima did not develop, lesions were rich in macrophages and lymphocytes. This approach can be useful in defining patients at risk of restenosis.

Aged↗

Cell composition of the human pulmonary valve: a comparative study with the aortic valve--the VESALIO Project. Vitalitate Exornatum Succedaneum Aorticum labore Ingegnoso Obtinebitur.

BACKGROUND: Cell populations present in human semilunar valves have not been investigated thoroughly. The aim of this study was to characterize the cell phenotypes in pulmonary valve leaflets (PVL) in comparison with aortic (AVL) valve leaflets. METHODS: AVL and PVL were dissected from hearts (n = 4) harvested from transplanted patients. Leaflets were processed for immunocytochemistry analysis and Western blotting procedures using a panel of monoclonal antibodies specific for cytoskeletal/contractile antigens. RESULTS: The fibrosa and the ventricularis layers of AVL had a higher cellularity than PVL. In PVL and AVL most cells were reactive for vimentin and nonmuscle (NM) myosin, though vimentin-positive cells were more abundant in AVL than in PVL. Sparse cells positive to anti-smooth muscle (SM) alpha-actin, calponin, and anti-SM myosin antibodies were found only at the outer edge of fibrosa. In Western blotting, AVL and PVL extracts were shown to be equally reactive for vimentin, SM alpha-actin, and NM myosin, whereas both valves were negative for SM myosin and SM22. CONCLUSIONS: Three distinct cell phenotypes have been identified in both valves: fibroblasts, myofibroblasts, and fetal-type SM cells whose distribution is specifically related to the valve layers. Although PVL and AVL cell populations differ quantitatively, some minor qualitative differences exist for vimentin and NM myosin distribution. These data are essential for studies aimed at repopulating valve scaffolds by using tissue engineering technology.

Actins↗

Effect of blood pressure and physical activity on carotid artery intima-media thickness in stage 1 hypertensives and controls.

The aim of the study was to investigate whether hypertension and physical training induce parallel changes in the arterial wall. Ninety-seven never-treated stage 1 hypertensive patients (HT) (systolic blood pressure 140 to 159 mm Hg or diastolic blood pressure 90 to 99 mm Hg) aged 18 to 45 years taking part in the Hypertension and Ambulatory Recording Venetia Study and 27 normotensive volunteers (NT) aged 30 +/- 9 years were studied. Data on physical or sports activity were collected and scored, and target organ involvement was investigated by assessing microalbuminuria, echocardiography, and carotid ultrasound study. The carotid arteries were examined according to the Atherosclerosis Risk in Communities protocol. Mean (m-IMT) and maximal (M-IMT) carotid intima-media thickness were measured at end-diastole in the far wall common carotid artery, in the bulb and internal carotid artery, in the lateral and posterior projection, averaging the left and right sides. A comparable level of physical activity was present in HT patients and NT subjects. Twenty-four-hour blood pressure and blood lipid levels, as well as target organ damage, were similar in physically active and sedentary HT. The m-IMT of the common carotid was greater in sedentary HT than in sedentary NT, as well as in active than in sedentary NT. The m-IMT of the internal carotid artery was also greater in active HT than in active NT, as well as in active than in sedentary HT. In logistic regression, comparing the first and fourth quartile of m-IMT, scored physical activity was a predictor of m-IMT in the internal carotid artery. No statistical interaction was found between physical activity and hypertension, indicating that these two items have a cumulative effect and act independently of each other. Sedentary HT had significantly greater levels of M-IMT than sedentary NT in all sites but the bulbs; in the internal and common carotid arteries, HT exercisers had significantly greater M-IMT than NT exercisers. Therefore, physical activity appears to be an early independent predictor of carotid wall thickness. This factor should be taken into consideration in population-based studies aimed at investigating supraortic vessels as it can act as a confounder.

Adult↗

Cerebral perfusion in hypertensive patients: effects of lacidipine and hydrochlorothiazide.

Previous studies have shown areas of cerebral hypoperfusion in the frontal and parietal lobes of asymptomatic hypertensives, in the absence of extracranial carotid artery stenosis. The aims of the present study were: (a) to correlate the presence of focal cortical hypoperfusion with the presence of white matter lesions (WML), lacunae and extracranial carotid artery stenosis; and (b) to compare the effects on cerebral perfusion of the dihydropyridine calcium entry blocker lacidipine and of hydrochlorothiazide (HCTZ) in hypertensive patients with carotid artery stenosis. Forty-one patients (30 males, aged 40-75) with mild to moderate essential hypertension and with negative history for cerebrovascular diseases were investigated. Twenty-four had normal extracranial carotid arteries at echo-colourDoppler examination, while 17 had at least one 50-70% stenosis of the internal carotid artery (ICA). At computed tomography (CT) scan, five patients had one or more lacunar infarctions, four WML, three lacunar infarctions and WML, and 26 a normal CT scan. Three, with old cortical infarctions, were excluded from further analysis. The prevalence of lesions was significantly higher among the patients with carotid artery stenosis (44% vs. 29%; p < 0.05). Distribution of mean relative cortical perfusion (MRCP) of regions of interest [hexamethyl-propileneamine oxime-single photon emission tomography (SPET)] was not normal, with a negative skewness in patients with lacunae. MRCP was slightly but significantly reduced in patients with lacunae in comparison with hypertensives with normal CT scan and with WML. The asymmetry index of tracer distribution was significantly greater in the patients with lacunar infarctions and WML than in the hypertensive patients with normal CT scan, irrespective of the presence of internal carotid artery stenosis. Fifteen hypertensives (13 males, aged 55-75 years) with at least one moderate stenosis of ICA at duplex scanning were treated in a double-blind, randomised, parallel study with lacidipine (4-6 mg o.d.) or HCTZ (25-50 mg o.d.) for 3 months after a 4-week single-blind placebo period. At baseline, perfusion of the cortical and basal areas was similar in the stenotic and the contralateral side. Despite the fall in pressure, both treatments increased MRCP in the stenotic side and in the contralateral side. The lower the baseline perfusion, the larger its increase with treatment. The decrease of local cerebral vascular resistance was significantly greater with lacidipine than with HCTZ. We conclude that in hypertensive patients, the distribution of cerebral flow is uneven, mostly in the presence of small asymptomatic subcortical lesions and independently from internal carotid artery stenosis. Antihypertensive treatment with lacidipine and HCTZ reduces local cerebral resistance and corrects focal hypoperfusion without inducing steal effects in patients with ICA stenosis.

Adult↗

Fish oil supplementation prevents neointima formation in nonhypercholesterolemic balloon-injured rabbit carotid artery by reducing medial and adventitial cell activation.

We asked whether balloon-injured neointima formation in the presence of high/low serum cholesterol (CT) levels might be affected by dietary supplementation with fish oil (FO). To test this hypothesis, we examined the differentiation, proliferation, or apoptosis profile of smooth muscle cell (SMC) and adventitial cell response to a mild injury induced via a Fogarty catheter in the carotid artery of adult rabbits that had been fed a standard chow or 0.5% CT-enriched diet starting 4 weeks before the lesion. One week before surgery, animals received FO supplementation. This regimen was continued for the following 3 weeks. The effect of FO on the early proliferative/migratory response of carotid SMCs was also examined in 2- and 7-day-injured normocholesterolemic rabbits. As controls, animals subjected to 3-week endothelial injury and animals kept on a 7-week CT diet were used. Carotid cryosections from the various animal groups were evaluated for morphometry (image analysis), differentiation (immunofluorescence with monoclonal antibodies specific for smooth muscle markers, ie, myosin isoforms, SM22, and fibronectin), proliferation (bromodeoxyuridine incorporation), and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling). FO treatment significantly reduced the development of intimal thickening in normocholesterolemic rabbits but had no efficacy in the presence of relatively higher serum CT levels. At day 2 (adventitia) and day 7 (neointima, media, and adventitia), the proliferation index of SMCs in FO-treated injured rabbits was markedly lower than in untreated injured controls. Concomitantly with the antiproliferative effect, FO was able to decrease the size of 2 cell types involved in the cell growth response to endothelial injury, namely, the "fetal-type" medial SMC subpopulation and the fibroblast-derived adventitial myofibroblasts. Thus, in our experimental conditions, a low CT level is a permissive condition for FO to prevent neointima formation to a considerable extent. This event is attributable to the early postinjury effect of FO on SMC/adventitial cell proliferation/differentiation patterns.

Animals↗

Cerebral perfusion in hypertensives with carotid artery stenosis: a comparative study of lacidipine and hydrochlorothiazide.

Focal cerebral hypoperfusion is a common finding in uncomplicated hypertensives even in the absence of large vessel atherosclerosis, and neuropsychological deficits correlate with cerebral hypoperfusion in hypertensive patients with cerebral microangiopathy. We investigated the effects on cerebral perfusion of the dihydropiridine calcium antagonist lacidipine and of hydrochlorothiazide (HCTZ) in asymptomatic hypertensive patients with concomitant atherosclerosis of the carotid arteries. Fifteen essential hypertensives (including 13 males, aged 55-75 years) with at least one 30-60% stenosis of the internal carotid artery at echo-color Doppler examination were treated in a double-blind, randomized, parallel study with lacidipine (4-6 mg od) or HCTZ (25-50 mg od) for 3 months after a 4-week single-blind placebo period. Regional cerebral perfusion was assessed at baseline and at the end of the treatment period with HMPAO-SPECT. Relative perfusion of cortical and subcortical areas was calculated as the ratio between their tracer activity and that of the cerebellum. At baseline, mean relative perfusion (MRP) of the cortical and subcortical areas was similar in the stenotic and the contralateral side. Despite the fall in pressure, lacidipine increased MRP both in the cortical and in the subcortical areas, whereas HCTZ increased MRP only in the cortical areas. The mean change in local vascular resistance, adjusted for initial perfusion value, was -20 A.U. (arbitrary unit) with lacidipine and -12 A.U. with HCTZ (p < 0.001). These differential effects of antihypertensive drugs on subcortical perfusion may be of benefit in the long-term prevention of vascular dementia in hypertensive patients.

Aged↗

Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo.

BACKGROUND: The participation of endothelin-1 (ET-1) in the control of vascular tone in humans has been questioned, on the basis of the finding of subthreshold immunoreactive (ir) ET-1 plasma levels. However, because most ET-1 is secreted abluminally, it might attain a higher concentration in the tunica media than in plasma. Furthermore, evidence indicates that vascular smooth muscle cells (VSMCs) can synthesize ET-1 on stimulation in vitro. We therefore looked for irET-1 in the different layers of the wall of human arteries, including renal, gastric, and internal thoracic artery wall, obtained ex vivo from consenting patients with coronary artery disease and/or high blood pressure undergoing surgery, as well as from young organ donors. METHODS AND RESULTS: We performed immunohistochemistry with specific anti-ET-1 and anti-vWF antibodies followed by detection with an avidin-biotin complex ultrasensitive kit. The presence of preproET-1 and human endothelin-converting enzyme-1 (hECE-1) mRNA was also investigated by reverse transcription-polymerase chain reaction in homogenates of vessel wall, including preparations deprived of both endothelium and adventitia, and in isolated VSMCs. We detected irET-1 in the endothelium of all arteries and in the tunica media of internal thoracic artery from most patients with coronary artery disease. PreproET-1 and hECE-1 mRNA was also detected in VSMCs isolated from these vessels. irET-1 and irvWF staining in endothelium and tunica media was measured by use of microscope-coupled computer-assisted technology. Significant correlations between the amount of irET-1 in the tunica media and mean blood pressure (P<0.05), total serum cholesterol (P<0.05), and number of atherosclerotic sites (P<0.001) were found. Thus, in organ donors, irET-1 was detectable almost exclusively in endothelial cells, whereas in patients with coronary artery disease and/or arterial hypertension, sizable amounts of irET-1 were detectable in the tunica media of different types of arteries. In addition, VSMCs isolated from these vessels coexpressed the preproET-1 and hECE-1 genes. CONCLUSIONS: Collectively, these findings are consistent with the contention that endothelial damage occurs in most patients with atherosclerosis and/or hypertension and that ET-1 is synthesized in VSMCs of these patients.

Adult↗

Effects of a traditional lifestyle on the cardiovascular risk profile: the Amondava population of the Brazilian Amazon. Comparison with matched African, Italian and Polish populations.

OBJECTIVE: To determine the relationships between lifestyle and cardiovascular risk factors among the Brazilian Amondava, one of the world's most isolated populations. DESIGN: Cross-sectional, population-based study. Four age- and sex-matched samples from Brazil Africa, Italy and Poland, representing different levels of modernization, were compared. Body weight, height, blood pressure, serum cholesterol and glycaemia were measured, and a standard questionnaire administered. Data concerning dietary habits and physical activity were collected. A personal socio-economic score was calculated, on the basis of type of economy, level of formal education, type of occupation, type of habitat, availability of piped water and electricity, main source of income, housing conditions, availability of radio, television or personal computer, knowledge of a second language, and organized health facilities. SETTING: Primary epidemiological screening, at an institution. RESULTS: Among the Amondava blood pressure was always <140/90 mm Hg, it did not increase with age and was not correlated with any other variable; 46.6% of subjects had systolic blood pressure <100 mm Hg. Blood pressure among the Amondava (109.6+/-11.1/69.5+/-6.4 mm Hg) was on average lower (P<0.0001) than in all other samples. Among the Amondava, the concentration of total cholesterol was always <200 mg/dl, i.e. similar to that of Africans whose diet included large amounts of vegetable foodstuffs; 90% had glycaemia (<80 mg/dl), and their mean value was the lowest (55.1+/-14.9 mg/dl) of all the groups. CONCLUSIONS: In addition to a possible genetic predisposition not analysed in this study, a traditional lifestyle (no contact with civilization, diet based on complex carbohydrates and vegetables, high energy expenditure) may protect against the development of hypertension, hypercholesterolaemia, and diabetes.

Adolescent↗

Factors underlying the increase in carotid intima-media thickness in borderline hypertensives.

To define the role played by various risk and behavioral factors in the increase of carotid intima-media thickness (IMT) observed in borderline hypertensives. Using B-mode ultrasonography, we compared 97 borderline hypertensives enrolled in the HARVEST study to 27 normotensive controls. Intima-media thickness was measured in the right and left common carotid artery, bulb, and internal carotid artery. Mean IMT (m-IMT), maximum IMT (M-IMT), the mean of M-IMT (M-MAX), and the prevalence of raised lesions (IMT>1 mm) were established. Compared to the controls, higher systolic BP, diastolic BP, mean arterial blood pressure levels and body mass index (BMI) were present in the borderline hypertensives, whereas age, smoking, physical activity, serum cholesterol, and triglycerides were similar. After adjusting for age, sex, heart rate, BMI, smoking, serum cholesterol, triglycerides, and physical activity, higher values of m-IMT and M-IMT were present in most carotid segments of borderline hypertensives compared with controls. After further adjustment for systolic BP and diastolic BP, differences were no longer significant. The adjusted M-MAX was 0.59+/-0.12 in borderline hypertensives compared with 0.50+/-0.10 in controls (P<0.001). After adjustment for systolic BP and diastolic BP it was 0.58+/-0.11 in borderline hypertensives compared with 0.50+/-0.12 in controls (P<0.005). In the various carotid segments, the prevalence of raised lesions was 1. 2% in borderline hypertensives compared with 0.3% in controls (P<0. 001). In the multivariate analysis m-IMT, M-IMT, and M-MAX were related to ambulatory mean arterial pressure, systolic BP and diastolic BP, serum cholesterol and triglycerides, BMI, age, and physical activity. Higher IMT values were found in subjects who were physically active than in those who were sedentary. In borderline hypertensives, an increase in IMT takes place not only in the common carotid artery but also in the bulb and the internal carotid segment. Blood pressure levels are a main determinant of m-IMT while the interaction of BP with other risk factors such as age and plasma lipids is more relevant for advanced intima-media thickening such as M-MAX.

Adult↗

Fish intake, independent of apo(a) size, accounts for lower plasma lipoprotein(a) levels in Bantu fishermen of Tanzania: The Lugalawa Study.

Plasma lipoprotein(a) [Lp(a)] levels are largely genetically determined by sequences linked to the gene encoding apolipoprotein(a) [apo(a)], the distinct protein component of Lp(a). Apo(a) is highly polymorphic in length due to variation in the numbers of a sequence encoding the apo(a) kringle 4 domain, and plasma levels of Lp(a) are inversely correlated with apo(a) size. In 2 racially homogeneous Bantu populations from Tanzania differing in their dietary habits, we found that median plasma levels of Lp(a) were 48% lower in those living on a fish diet than in those living on a vegetarian diet. Considering the relationship between apo(a) size and Lp(a) plasma concentration, we have extensively evaluated apo(a) isoform distribution in the 2 populations to determine the impact of apo(a) size in the determination of Lp(a) values. The majority of individuals (82% of the fishermen and 80% of the vegetarians) had 2 expressed apo(a) alleles. Additionally, the fishermen had a high frequency of large apo(a) isoforms, whereas a higher frequency of small isoforms was found in the vegetarians. When subjects from the 2 groups were matched for apo(a) phenotype, the median Lp(a) value was 40% lower in Bantus on the fish diet than in those on the vegetarian diet. A significant inverse relationship was also found between plasma n-3 polyunsaturated fatty acids and Lp(a) levels (r=-0.24, P=0.01). The results of this study are consistent with the concept that a diet rich in n-3 polyunsaturated fatty acids, and not genetic differences, is responsible for the lower plasma levels of Lp(a) in the fish-eating Bantus and strongly suggest that a sustained fish-based diet is able to lower plasma levels of Lp(a).

Adult↗