Defining patients at extremely high risk for coronary artery disease in heterozygous familial hypercholesterolemia.

AIM: Heterozygous patients with familial hypercholesterolemia (FH) are known to be associated with a high risk of coronary artery disease (CAD), which is a major determinant of their clinical outcome. The prognosis of heterozygous FH patients substantially varies, being dependent on the level of their CAD risk, and their therapeutic regimen should be individualized. We assessed critical levels of LDL-cholesterol (LDL-C) and Achilles tendon thickness (ATT) to identify heterozygous FH patients at "very high" risk for CAD. METHODS: One hundred and nine heterozygous FH patients who had no history of CAD and had had their plasma lipid profile and ATT assessed before treatment were followed up until their first CAD event or 31 December 2010. Multivariable logistic regression models were used to analyze the correlation of LDL-C and/or ATT levels with the risk of developing CAD. RESULTS: During the follow-up period, 21 of the 109 patients had a CAD event, diagnosed by coronary angiogram. Individuals in the highest tertile of LDL-C had a CAD risk 8.29-fold higher than those in the lowest tertile. Individuals in the highest tertile of the ATT group had a 7.82-fold higher CAD risk than those in the lowest tertile. Those who had either LDL-C ≥ 260 mg/dL or ATT ≥ 14.5 had a 23.94-fold higher CAD risk than those with LDL-C < 260 mg/dL and ATT <14.5 mm. CONCLUSIONS: In heterozygous FH patients, LDL-C 260 mg/dL or higher and/or ATT 14.5 mm or thicker are useful markers for extracting patients at "very high" risk for CAD.

Impact of statin treatment on the clinical fate of heterozygous familial hypercholesterolemia.

AIM: Familial hypercholesterolemia (FH) patients are at particular risk for premature coronary artery disease (CAD) caused by high levels of low density lipoprotein (LDL). Administration of statins enabled us to reduce LDL-C levels in heterozygous FH patients. To evaluate the impact of statins on the clinical fate of heterozygous FH, a retrospective study was performed. METHODS: We analyzed the clinical influence of statins on age at the first clinical onset of CAD in 329 consecutive FH patients referred to the lipid clinic of the National Cardiovascular Center. Among 329 heterozygous FH patients, the onset of CAD was identified in 101. RESULTS: The age at onset of CAD was 58.8+/-12.5 years in the 25 patients on statins at onset, significantly higher than that in the 76 patients not on statins (47.6+/-10.5 years) (p <0.001). The average age at CAD onset was significantly higher after widespread use of statins (54.2+/-13.2 years in 48 patients, Group 1) compared to before October 1989 when statins were approved in Japan (46.9+/-9.6 years in 53 patients; Group 2, p=0.002). A significant difference was seen between Groups 1 and 2 in the variables, including sex, prevalence of smoking habit, LDL-C, and the use of statins, aspirin and probucol. After adjusting for these variables, only statin use was independently associated with the difference in age at CAD onset by multivariable analysis. CONCLUSION: Statins have improved the clinical course of patients with heterozygous FH.

Association of plasma B-type natriuretic peptide levels with obesity in a general urban Japanese population: the Suita Study.

The inverse association between plasma B-type natriuretic peptide (BNP) levels and body mass index (BMI) has been reported in Western populations. Here we analyzed the relationship between plasma BNP and obesity in a general urban Japanese population. We recruited 1,759 subjects without atrial fibrillation or history of ischemic heart disease aged 38-95 years (mean age +/- standard deviation 64.5 +/- 10.9 years, 56.1% women, mean BMI 22.8 +/- 3.1 kg/m(2)) from the participants in the Suita Study between August 2002 and December 2003. In multivariable regression analyses adjusted for age, systolic blood pressure, pulse rate, serum creatinine, left ventricular hypertrophy in ECG, the inverse relationships between BNP levels and BMI (kg/m(2)) was found in both sexes (both p<0.001). Multivariable-adjusted mean plasma BNP levels in the group of BMI<18.5, 18.5< or =BMI< 22, 22< or =BMI<25, and 25< or =BMI were 23.4, 17.9, 14.0 and 13.0 pg/mL, respectively (trend p<0.001). The negative association of body fat (percentage and mass), skin fold thickness, or waist circumference with BNP levels was observed the negative associations in both sexes (p<0.01). Among the obesity indices, body fat mass is most tightly associated with BNP. In conclusion, plasma BNP was inversely associated with obesity related markers such as body fat mass, skinfold thickness and waist circumferences after adjusted for relevant covariates in a Japanese population.

Visceral fat is negatively associated with B-type natriuretic peptide levels in patients with advanced type 2 diabetes.

AIMS: The association between BMI and low levels of B-type natriuretic peptide (BNP), a marker of heart failure, has been demonstrated in a large population-based cohort. We examined the effects of obesity on BNP levels in patients with diabetes that are often associated with obesity and a higher risk for heart failure. METHODS: Plasma BNP levels, BMI, and cardiac function parameters were measured in 608 patients with type 2 diabetes. A computed tomography scan was performed to measure abdominal fat. RESULTS: In multivariable regression analyses adjusted for age, sex, systolic blood pressure, pulse rate, serum creatinine, asynergy, left atrial dimension, percent fractional shortening, and left ventricular mass, there was an inverse relationship between BMI and BNP (p<0.001). Obese individuals with 25

Pioglitazone treatment stimulates circulating CD34-positive cells in type 2 diabetes patients.

Circulating bone marrow derived immature cells, including CD34-positive (CD34(+)) cells, contribute to maintenance of the vasculature, not only as a pool of endothelial progenitor cells (EPCs), but also as a source of growth/angiogenesis factor. We hypothesized that the thiazolidineone compound pioglitazone could stimulate the circulating CD34(+) cells in diabetic patients. Thirty-four patients with type 2 diabetes received 15-30 mg pioglitazone for 24 weeks. The number of circulating CD34(+) cells significantly increased at 12 and continued this effect for 24 weeks (1.08+/-0.39, 1.34+/-0.34 and 1.32+/-0.28cells/microl at 0, 12 and 24 weeks, respectively). The change of CD34(+) cell levels (DeltaCD34(+) cells) between 0 and 12 weeks was significantly correlated with the change of high sensitive C reactive protein levels (Deltahs-CRP) and change in adiponectin levels (Deltaadiponectin) (r=-0.412, r=0.359, respectively). Our study demonstrated that pioglitazone treatment increased circulating CD34(+) cells, suggesting that this effect may at least partly contribute to the anti-atherosclerotic action of pioglitazone.