Influence of Genetic Risk Factors on Coronary Heart Disease Occurrence in Afro-Caribbeans.

BACKGROUND: Despite excessive rates of cardiovascular risk factors such as hypertension, diabetes, and obesity, Afro-Caribbeans have lower mortality rates from coronary heart disease (CHD) than do whites. This study evaluated the association of genetic risk markers previously identified in whites and CHD in Afro-Caribbeans. METHODS: We studied 537 Afro-Caribbean individuals (178 CHD cases and 359 controls) who were genotyped for 19 CHD-related single-nucleotide polymorphisms (SNPs). A genetic risk score (GRS) incorporating the 19 SNPs was calculated. These participants were compared with 1360 white individuals from the Second Northwick Park Heart Study. RESULTS: In Afro-Caribbeans, patients with CHD had higher rates of hypertension (78.7% vs 30.1%), hypercholesterolemia (52.8% vs 15.0%), and diabetes (53.9% vs 14.8%) and were more often men (64.0% vs 43.7%) and smokers (27.5% vs 13.4%) compared with non-CHD controls (all P < 0.001). The GRS was higher in Afro-Caribbeans with CHD than in those without CHD (13.90 vs 13.17; P < 0.001) and was significantly associated with CHD after adjustment for cardiovascular risk factors, with an odds ratio of 1.40 (95% confidence interval, 1.09-1.80) per standard deviation change. There were significant differences in allelic distributions between the 2 ethnic groups for 14 of the 19 SNPs. The GRS was substantially lower in Afro-Caribbean controls compared with white controls (13.17 vs 16.59; P < 0.001). CONCLUSIONS: This study demonstrates that a multilocus GRS composed of 19 SNPs associated with CHD in whites is a strong predictor of the disease in Afro-Caribbeans. The differences in CHD occurrence between Afro-Caribbeans and whites might be a result of significant discrepancies in common gene variant distribution.

Distribution of coronary artery disease severity and risk factors in Afro-Caribbeans.

BACKGROUND: Traditional risk factors are strong predictors of the incidence of coronary artery disease (CAD), but their association with disease severity remains controversial and could differ across ethnic groups. AIMS: In this study, we assessed the prevalence of cardiovascular risk factors (CRFs) in Afro-Caribbean patients with documented CAD, and sought to identify which of these factors are related to disease severity. METHODS: We retrospectively studied 420 consecutive patients with CAD. Disease severity was determined from the results of invasive coronary angiography, based on the presence or absence of multiple (two or three) diseased vessels and the myocardial jeopardy (MJ) score. RESULTS: In the studied population (mean age 64.7 ± 12.4 years), hypertension, diabetes and dyslipidaemia were the most frequent modifiable CRFs, present in 75.9, 47.8 and 37.8% of patients, respectively. Multiple logistic regression analysis showed that diabetes, male sex and personal cardiovascular history significantly increased the risk of multivessel CAD: odds ratios (ORs) of 1.53 (1.01-2.33; P=0.048), 1.61 (1.02-2.55; P=0.043) and 1.68 (1.11-2.56; P=0.015), respectively. Obesity was an independent negative predictor, with an OR of 0.48 (0.29-0.79; P=0.004). Other traditional CRFs (hypertension, dyslipidaemia, smoking, age and family history of vascular disease) were not associated with CAD severity. For high-risk lesions (MJ score ≥8), both diabetes and hypertension were independent predictors of disease severity, whereas obesity was no longer a protective factor. CONCLUSION: Diabetes emerged as the strongest modifiable risk factor predictor of multivessel disease in Afro-Caribbean patients, whereas obesity was an independent protective factor. The underlying mechanisms of these associations should be relevant to disease prevention.

Are G3 ENETS neuroendocrine neoplasms heterogeneous?

The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung NEC. To characterize the subgroup of non-small-cell-type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathological features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small-cell-type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Twenty-eight patients (17%) fulfill the inclusion criteria. Tumors were classified as well-differentiated NET (G3-WDNET) in 42.8% of cases and poorly differentiated, large-cell NEC (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or neuron-specific enolase were elevated in 42 and 25% respectively of G3-WDNET and 31 and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88 and 50% of G3-WDNET or G3-LCNEC respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified as G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P=0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (P=0.049). G3 ENETS GEP and thoracic neuroendocrine neoplasms (NEN) could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis, and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.

Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury. METHODS: ANP gene transfer was performed using a recombinant adenovirus containing the ANP cDNA controlled by the Rous sarcoma virus (RSV) long terminal repeat (Ad-RSV-ANP). A recombinant adenovirus expressing the RSV-controlled ß-galactosidase gene (Ad-RSV-ß-gal) was used as the control. Rat VSMC culture was used for in vitro studies. In the in vivo experiments, carotid arteries were analyzed after balloon injury and local infusion of the viral solution. RESULTS: VSMCs transfected by Ad-RSV-ANP produced a significant amount of ANP detected by immunoreactive assay and accumulated about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days after injury, neointimal formation and the intima/media ratio were reduced by 25% and 28%, respectively, in the Ad-RSV-ANP-treated group compared to the control group. CONCLUSIONS: The present study demonstrates the efficacy of recombinant adenovirus Ad-RSV-ANP with respect to inhibiting rat VSMC proliferation and migration. Our findings also provide evidence that ANP is implicated in the modulation of vascular remodeling following endothelial injury.

Vitamin D status in dark-skinned patients undergoing hemodialysis in a continually sunny country.

BACKGROUND: Vitamin D (vitD) insufficiency is common in end-stage renal disease. Seasonal and ethnic differences in vitD status have been reported previously. We hypothesized that vitD status in Afro-Caribbean patients on hemodialysis (HD) living in a country with a constant sunny climate would be better than that in African-American HD patients living in countries with a winter season. METHOD: A cross-sectional study was conducted in 152 Afro-Caribbean HD patients in a dialysis center located in Guadeloupe. We evaluated the prevalence of vitD insufficiency, defined as serum 25-hydroxyvitamin D (25(OH)D) levels below 30 ng/mL, compared with those results previously reported in African-American HD patients (88%). RESULTS: Prevalence of vitD insufficiency was 60% and thus lower than that in the African-American patients considered as the reference population (p<0.001). In our diabetic patients, this prevalence was 72.4%. Globally, 9.2% of patients had 25(OH)D below 15 ng/mL. Alfacalcidol therapy was prescribed in 29%. Mean 25(OH)D levels were higher in treated than in untreated patients (32 vs. 27 ng/mL; p=0.009). Patients with vitD insufficiency had dyslipidemia and diabetes more frequently. No significant differences were found between patients with and without vitD insufficiency for serum calcium, phosphorus and parathyroid hormone (PTH). In untreated patients, no significant correlation was found between 25(OH)D and PTH levels. CONCLUSION: Prevalence of vitD insufficiency in Afro-Caribbean HD patients was lower than that previously reported in African Americans undergoing HD in the United States. This finding may be due to the constantly sunny weather with a high intensity of UVB radiation in Guadeloupe.

[Half of the patients with primary hyperparathyroidisms have a vitamin D deficiency: aggravating the osseous attack]. / La moitié des patients atteints d'hyperparathyroïdies primaires ont un déficit en vitamine D aggravant l'atteinte osseuse.

BACKGROUND: Primary hyperparathyroidism (PHPT) associates hypocalcemia and hypophosphatemia secondary to parathyroid hormone (PTH) excess. PHPT is asymptomatic for 80% of patients and responsible for a decrease in bone mineral density particularly in women. Vitamin D deficiency increases the risk of bone fractures. METHODS: We performed a prospective analysis of patients with PHPT in order to evaluate the prevalence of vitamin D deficiency. We determined the effects of vitamin D deficiency on bone metabolism: calcium, phosphate and PTH levels. We also analyzed biochemical markers of bone remodeling and bone mineral density (BMD) before and 6 months after vitamin D replacement. RESULTS: 75 patients with PHPT were identified: 38 patients with vitamin D deficiency but only 22 patients could be followed (G1). 14 patients with a normal level of vitamin D were followed (G2). Prevalence of vitamin D deficiency was 51%. Calcium and phosphate levels were similar into both groups. PTH levels were higher in the G1 group. Calciuria was significantly lower in the G1. For markers of bone formation (fragments of collagen CTX and alkaline phosphatase): osteocalcine levels were higher in G1 group. For bone resorption: télopeptides levels were significantly higher in the G1 group. T score was significantly lower in this group, favoring a significant osseous attack. After 6 months of substitution with vitamin D, calcium decreased and hypophosphatemia normalized. PTH levels decreased (-50.7%). Calciuria increased without risks of urinary lithiasis. Bone mineral density loss decreased while markers of bone turn over increased. DISCUSSION: Vitamin D deficiency increases the risk of bone fragility in PHPT. Few data are available in France concerning the prevalence of vitamin D deficiency in PHPT. Our results were similar to data in other countries. Vitamin D replacement with regular monitoring of calcium and calciuria levels is beneficial for metabolic and hormonal status, improves bone density, without systematic opposing effects. The follow-up of effectiveness by BMD could be associated with measurement of markers of bone remodeling. CONCLUSION: In asymptomatic PHPT, particularly those for which surgery is not indicated, measurement of 25 OH Vitamin D should be systematic. It is recommended before surgery.

Body mass index (BMI) and waist circumference (WC) as screening tools for cardiovascular risk factors in Guadeloupean women.

Hypertension, dyslipidemia and type 2 diabetes, important cardiovascular risk factors, are strongly linked to obesity. Body mass index (BMI) and waist circumference (WC) are measures of obesity that can be useful in identifying individuals with these risk factors. We assessed which of the two measures is more informative at the population level. The study population included 5,149 consecutive women aged 18 to 74 recruited in an Health Center of Guadeloupe (FWI) in 1999. The areas under the ROC curves of BMI and WC and their 95% CI were computed and compared. Logistic regression analysis of BMI and WC and the areas under the ROC curves in two separate age groups (18-39 years and 40-74 years) showed that age modifies the discriminant ability of these parameters in identifying the CVD risk factors. Sensitivity equalled specificity at levels between 52-70% for BMI and 55-80% for WC. ROC areas for identifying each risk factors by BMI varied from 0.52 to 0.84 and by WC from 0.55 to 0.88. For the identifying of women with at least one CVD risk factor, in the whole population, the areas under the curves for BMI and WC (respectively, 0.71; 95% CI: 0.69-0.73 and 0.76; 95% CI: 0.74-0.78) were both significantly greater than 0.5. The difference between these correlated areas was 0.04, 95% CI [-0.05, -0.03]. The lowest values of the areas were noted in detecting women with dyslipidemia and the highest in detecting those with type 2 diabetes. Waist circumference, a practical tool that had a higher discriminant ability than BMI in identifying presence or absence of all these risk factors, appears as the best screening tool in this population.