Prevalence of treatment for diabetes during 1997-2007, and trends in cardiovascular risk factors between 2001 and 2007 according to diabetic treatment, in the IPC (Investigations Préventives et Cliniques; Preventive and Clinical Investigations) cohort.

AIM: This study aimed to evaluate changes in the prevalence of glucose-lowering agents in a large, unselected general French population from 1997 to 2007, with specific focus on changes in other cardiovascular risk factors in relation to diabetic status during 2001-2002 and 2006-2007. METHODS: The prevalence of treated diabetes was assessed in a large population who had a health check-up at the "Investigations Préventives et Cliniques" Center between 1997-2007. Baseline characteristics and risk profiles of individuals with and without treatment for diabetes were assessed and compared with data for 2001-2002 and 2006-2007. RESULTS: From 1997 to 2007, the prevalence of treatment for diabetes increased from 0.75% to 1.73% in men and from 0.7% to 2.28% in women. In 2006-2007 compared with 2001-2002, the odds ratios for receiving glucose-lowering agents, adjusted for age, body mass index (BMI) and educational level, were 1.54 (95% CI: 1.28-1.86) in men and 1.59 (95% CI: 1.26-2.03) in women. In those treated for diabetes compared with untreated subjects, greater decreases in blood pressure, cholesterol and glycaemia were found, stress and depression scores improved, and a greater increase in BMI was found. Smoking decreased in both treated and untreated individuals. Physical activity decreased in treated individuals, but remained unchanged in the general population. CONCLUSION: The prevalence of people treated with diabetes increased in the Paris area. Although most concomitant risk factors decreased more in treated individuals than in the general population, physical activity and BMI worsened, thus, emphasizing the need for improving patient education.

Comparative biology of tropical Lethrinus species (Lethrinidae): challenges for multi-species management.

Life-history characteristics of six tropical Lethrinus species sampled from the Great Barrier Reef World Heritage Area were compared. Two species groups were identified based on fork length (LF ): large species with maximum LF > 640 mm (longface emperor Lethrinus olivaceus, yellowlip emperor Lethrinus xanthochilus and spangled emperor Lethrinus nebulosus) and small species with maximum LF < 480 mm (Pacific yellowtail emperor Lethrinus atkinsoni, pink ear emperor Lethrinus lentjan and ornate emperor Lethrinus ornatus). Lifespan was not correlated with LF . Early growth for all species was rapid and similar during the first few years of life, but coefficients of the von Bertalanffy growth function varied considerably among species. Growth also differed between sexes for L. atkinsoni. Reproductive characteristics varied among species, with peak periods of spawning occurring in November to December for L. atkinsoni, July to August for L. nebulous, September to October for L. olivaceus and a protracted season for L. lentjan, although fewer samples were available for the last two species. Sex-specific LF and age distributions and gonad histology of L. lentjan were suggestive of a functional protogynous reproductive pattern, as observed in other lethrinids. Gonad histology indicated non-functional protogynous hermaphroditism for L. atkinsoni and L. nebulosus. The diversity of life histories among these closely related species emphasizes the difficulty in devising single management strategies appropriate for multi-species fisheries and illustrates the importance of understanding species-specific life histories to infer responses to exploitation.

Impact of socioeconomic status on diabetes and cardiovascular risk factors: results of a large French survey.

AIM: This study examined the association between deprivation and diabetes in a large French population, and evaluated the impact of deprivation on diabetes after taking in account a number of confounding factors. METHODS: A total of 32,435 men and 16,378 women, aged 35 to 80 years, who had a health checkup at the "Centre d'Investigations Préventives et Cliniques" (IPC Centre: a preventive medical center in Paris, France), between January 2003 and December 2006, were evaluated. Socioeconomic deprivation was assessed using the EPICES score. The most deprived subjects were those in the fifth quintile of score distribution. RESULTS: Several cardiovascular risk markers increased significantly in deprived subjects. In both genders, deprivation was associated with deleterous health status and lifestyle habits. In women, BMI, central obesity and the metabolic syndrome were associated with deprivation. The prevalence of diabetes increased with deprivation level. Compared with the first quintile of EPICES score distribution, the prevalence of diabetes was three to eight times higher in the fifth quintile. After taking into account age, and biological, clinical and lifestyle parameters, the risk of diabetes onset (odds ratio) among deprived vs. non-deprived subjects was 2.54 (95% CI: 1.99-3.24) in men and 2.2 (95% CI: 1.44-3.35) in women. CONCLUSION: In the general French population, deprivation was associated with deleterious health status and lifestyle. Risk of diabetes increased linearly with deprivation level and, after taking into account various confounding factors, the risk of diabetes remained significantly higher among deprived subjects. Other factors such as nutrition should now be examined to explain the excess risk of diabetes among the most deprived people.

[Incidence of arterial hypertension in French population after 60 years]. / Incidence de l'hypertension artérielle dans la population française de plus de 60ans.

OBJECTIVE: To evaluate incidence and determinants of arterial hypertension after 60 years. METHODS: Four thousand nine hundred and forty one subjects aged 60 years or above (2505 men: 64.2±4.2 years; 2436 women: 64.8±4.3 years) were explored two times at the IPC center, Paris, between 1992 and 2007, and were normotensive at the first visit (V1): systolic BP (SBP) less than 140mmHg and diastolic BP (DBP) less than 90mmHg without treatment. The delay between the two visits was 5.8±2.2 years. At the second visit, population was analysed as normotensives and hypertensives. An age-adjusted Anova compared groups. RESULTS: In men, incidence of hypertension is 41.5% and 25.9% for isolated systolic hypertension. In women, incidences were 37.8% and 27.8% respectively. Baseline characteristics for V2-hypertensives showed higher SBP, DBP, BMI, heart rate, glycemia, ECG abnormalities thanV2-normotensives but they had lower physical activity. The determinants of hypertension were: SBP, age, BMI, DBP, glycemia, and lack of physical activity for this age class. CONCLUSION: From 60 years old, 6-year incidence of hypertension is about 40% and 26% for isolated systolic hypertension, this latter being higher in women. Regular physical activity is protective.

Engineered silica nanocarriers as a high-payload delivery vehicle for antioxidant enzymes.

Antioxidant enzymes for the treatment of oxidative stress-related diseases remain a highly promising therapeutic approach. As poor localization and stability have been the greatest challenges to their clinical translation, a variety of nanocarrier systems have been developed to directly address these limitations. In most cases, there has been a trade-off between the delivered mass of enzyme loaded and the carrier's ability to protect the enzyme from proteolytic degradation. One potential method of overcoming this limitation is the use of ordered mesoporous silica materials as potential antioxidant enzyme nanocarriers. The present study compared the loading, activity and retention activity of an anti-oxidant enzyme, catalase, on four engineered mesoporous silica types: non-porous silica particles, spherical silica particles with radially oriented pores and hollow spherical silica particles with pores oriented either parallel to the hollow core or expanded, interconnected bimodal pores. All these silica types, except non-porous silica, displayed potential for effective catalase loading and protection against the proteolytic enzyme, pronase. Hollow particles with interconnected pores exhibit protein loading of up to 50 wt.% carrier mass, while still maintaining significant protection against proteolysis.

Waist circumference and mortality: impact of associated risk factors.

AIM: This study was designed to evaluate the risks of all-cause and cardiovascular mortality in subjects with large waist circumferences, with or without associated risk factors, and to determine whether or not waist circumference might identify high-risk subjects. METHODS: The population included 55,800 men (aged 52.1 ± 8.2 years) and 28,937 women (aged 54.2 ± 9.1 years) who had undergone a health checkup at the Preventive and Clinical Investigations Centre between January 1999 and December 2004 with a mean follow-up of 4.7 ± 1.7 years. An increased waist circumference was defined as those in the last quintile of distribution. Mortality risk for each waist-circumference quintile, with or without associated risk factors (hypertension, diabetes, elevated LDL cholesterol), was evaluated using Cox's regression models, including age, gender, tobacco and alcohol consumption, and physical activity. RESULTS: The percentage of subjects with hypertension, diabetes and raised LDL cholesterol levels increased from the first waist-circumference quintile to the last. After adjusting for variables, all-cause mortality risk did not increase significantly with large waist circumference only (HR: 1.19 [0.84-1.68]), but was significantly higher when an increased waist circumference was associated with at least one risk factor (HR=1.58 [1.26-1.98]; 3.70 [2.05-6.68] for three risk factors). Similar results were observed for cardiovascular mortality (HR: 0.85 [0.19-3.68] with only large waist circumference and 3.56 [2.05-6.57] when waist circumference was associated with at least one risk factor). CONCLUSION: In a population with low-to-moderate mortality risk, waist circumference alone did not identify high-risk subjects, thus suggesting that a more global approach is necessary.

Relationship between alcohol intake, health and social status and cardiovascular risk factors in the Urban Paris-Ile-de-France Cohort: is the cardioprotective action of alcohol a myth?

BACKGROUND/OBJECTIVES: Observational studies document the inverse relationship between cardiovascular disease (CVD) and moderate alcohol intake. However, the causal role for alcohol in cardioprotection remains uncertain as such protection may be caused by confounders and misclassification. The aim of our study was to evaluate potential confounders, which may contribute to putative cardioprotection by alcohol. SUBJECTS/METHODS: We evaluated clinical and biological characteristics, including cardiovascular (CV) risk factors and health status, of 149,773 subjects undergoing examination at our Center for CVD Prevention (The Urban Paris-Ile-de-France Cohort). The subjects were divided into four groups according to alcohol consumption: never, low (30 g/day); former drinkers were analyzed as a separate group. RESULTS: After adjustment for age, moderate male drinkers were more likely to display clinical and biological characteristics associated with lower CV risk, including low body mass index, heart rate, pulse pressure, fasting triglycerides, fasting glucose, stress and depression scores together with superior subjective health status, respiratory function, social status and physical activity. Moderate female drinkers equally displayed low waist circumference, blood pressure and fasting triglycerides and low-density lipoprotein-cholesterol. Alcohol intake was strongly associated with plasma high-density lipoprotein-cholesterol in both sexes. Multivariate analysis confirmed that moderate and low drinkers displayed better health status than did never drinkers. Importantly, few factors were causally related to alcohol intake. CONCLUSIONS: Moderate alcohol drinkers display a more favorable clinical and biological profile, consistent with lower CV risk as compared with nondrinkers and heavy drinkers. Therefore, moderate alcohol consumption may represent a marker of higher social level, superior health status and lower CV risk.

Mapping of five resistance genes to sugar-beet powdery mildew using AFLP and anchored SNP markers.

Sugar-beet powdery mildew, caused by the fungus Erysiphe betae, now occurs in all sugar-beet growing areas and can reduce sugar yield by up to 30%. Powdery mildew resistant plants from three novel sources were crossed with sugar beet to generate segregating populations. Evaluation of resistance was carried out in artificially inoculated field and controlled environment tests. The resistance level in two of the sources was found to be significantly higher than that in currently available sugar-beet cultivars. AFLP analysis was used in combination with bulked segregant analysis to develop markers linked to the resistant phenotype in each population. Five dominant major resistance genes were identified and assigned the proposed symbols Pm2 to Pm6. Pm3 conferred complete resistance to powdery mildew; the other genes conferred high levels of partial resistance. From the use of anchoring SNP markers, two genes were located to chromosome II and three to chromosome IV. Two of the genes on chromosome IV mapped to the same location and one of the genes on chromosome II mapped to the same region as the previously identified Pm1 gene. With the availability of these genes there is now excellent potential for achieving durable resistance to sugar-beet powdery mildew, thus reducing or obviating the need for chemical control.

Cardiovascular risk markers associated with the metabolic syndrome in a large French population: the "SYMFONIE" study.

OBJECTIVE: The SYMFONIE study was designed to analyze the clinical and biological characteristics, and the cardiovascular risk markers, in men and women with the metabolic syndrome compared to control subjects. RESEARCH DESIGN AND METHODS: The study population included 101,697 men and women, 18 to 80 years of age, who had a health checkup at the Centre d'Investigations Preventives et Cliniques (Paris, France) between 1997 to 2002. The metabolic syndrome was defined according to the ATpiiI-NCEP 2001 criteria. RESULTS: Out of the 66,202 men (47.4+/-11.8 years) and 35,495 women (48.5+/-13.6 years) included in this population, 6761 men (10.2%) and 2155 women (6.1%) presented the metabolic syndrome. Among subjects < or =40 years of age, the prevalence of the metabolic syndrome was 5.0% in men and 2.2% in women, and rose to 14.1% and 12.0%, respectively, among men and women >70 years of age. After adjustment for age, patients with the metabolic syndrome presented higher pulse pressure (systolic minus diastolic blood pressure), higher heart rate, lower vital respiratory capacity, lower physical activity, an increase in inflammatory status assessed through leukocyte count and dental inflammation, hepatic abnormalities, and increased levels of stress and depression. CONCLUSION: In this large French population, the prevalence of the metabolic syndrome is lower than in North American and northern European populations. Patients with the metabolic syndrome present several additional hemodynamic, inflammatory and psychological risk markers which could contribute to the poor cardiovascular prognosis of these subjects.

[Prevalence of intraocular hypertension and glaucoma in a nonselected French population]. / Prévalence de l'hypertonie oculaire et du glaucome dans une population française non sélectionnée.

AIMS: To measure intraocular pressure (IOP) in a large human sample and to assess the prevalence of glaucoma with elevated IOP and ocular hypertension (OHT) in this population. METHODS: We measured IOP in 2,074 subjects (men: women: 1,384: 690). If the IOP was higher than 20 mmHg, a photograph of the optic disc was taken and the visual field was examined. The optic nerve head and the visual field were evaluated in 395 individuals. RESULTS: In men aged 18-39 years, mean IOP was 15.5+/-3.1 mmHg and 16.4+/-3.5 mmHg after 60 years of age. In women, IOP reached 14.5+/-3.3 and 15.9+/-3.1 mmHg, respectively. IOP greater than 21 mmHg was found in 10.1% of males and 6.4% of females. The prevalence of OHT increased with age: from 5.3% to 15.5% in men and from 3% to 7.5% in women for the same age ranges. A diagnosis of glaucoma with elevated IOP was made in 2.2% of males and 3.0% of females. The prevalence of glaucoma increased with age from 0.8% to 5.7% in men and from 0.6% to 4.7% in women under 40 years and over 60 years of age, respectively. DISCUSSION: This study confirms the increase in IOP with age and the role of aging in the prevalence of OHT and glaucoma with elevated IOP. CONCLUSION: This transversal study shows the feasibility of intraocular hypertension and glaucoma screening and prevalence assessment in a nonselected large population in France.

Patterns of parental relatedness and pup survival in the grey seal (Halichoerus grypus).

Levels of parental relatedness can affect offspring survival and susceptibility to disease. We investigated parental relatedness of live and dead Halichoerus grypus pups between and within island populations and between possible causes of mortality. Nine microsatellites were used to calculate internal relatedness (IR) and standardized mean d2. We find that pups with higher than average levels of IR have significantly lower survival and that this varied between island populations and that certain loci contributed to the effect more than others. Although, there were no significant differences between causes of mortality, peritonitis, infection and stillborn had the highest levels of IR. These results provide evidence that parental relatedness is an important determinant of pre-weaning pup survival in the grey seal and that this may vary with cause of mortality given a larger sample size.

Combined effects of systolic blood pressure and serum cholesterol on cardiovascular mortality in young (<55 years) men and women.

AIMS: To evaluate the combined effects of the two most frequent modifiable risk factors, systolic blood pressure and serum cholesterol, on cardiovascular and coronary mortality, in a large French population aged 18 to 55 years. METHODS AND RESULTS: We studied 108,879 men (mean age 39.1+/-9.4 years) and 84,931 women (mean age 37.3+/-10.0 years) who had a health check-up at the IPC Center between 1978 and 1988. Mortality data for a mean period of 13 years were analysed. Systolic blood pressure and cholesterol levels were classified according to the cut-points proposed by international guidelines. In men, the prevalence of high cholesterol was more than twice as high in hypertensives as in normotensives; in women, it was more than three times higher. The combination of these two risk factors has additive effects on cardiovascular disease and coronary heart disease risk. In men, a borderline elevation of both systolic blood pressure (130-139 mmHg) and cholesterol (200-239 mg x dl(-1)) leads to a three- to four-fold increase in cardiovascular disease risk. Men with systolic blood pressure >or=160 mmHg represent a small percentage (about 5%) who have a 10-fold increase in cardiovascular disease and coronary heart disease risk, especially when high cholesterol is present. In women of the same age, similar trends were observed, but the results were less significant, probably due to the low cardiovascular disease mortality rates. CONCLUSIONS: In conclusion, in French subjects under 55 years of age, a combination of high systolic blood pressure and high serum cholesterol dramatically increased cardiovascular disease and coronary heart disease risk, especially in men. A more aggressive public health policy is needed to prevent the development of risk factors in younger subjects.

Reduced pulmonary function is associated with central arterial stiffness in men.

The association of impaired pulmonary function with cardiovascular morbidity and mortality has been reported in several prospective studies. The nature of this association and the mechanisms underlying it are unknown. Both atherosclerosis and central arterial stiffness might be involved. We recently reported, in a 4-yr longitudinal study, that reduced lung function predicts the development of carotid atherosclerotic plaques. In the present study, we report the associations of aortic stiffness with lung function measurements. One hundred and ninety-four men, aged 30 to 70 yr and free of coronary heart disease, who volunteered for a standard health examination were included. FEV(1) and FVC were used to assess lung function. Aortic stiffness was estimated from the carotid-femoral pulse-wave velocity (PWV), which increases proportionally with an increase in aortic stiffness. PWV was significantly and negatively associated with FEV(1) and FVC (partial correlation coefficients adjusted for age and height: -0.27 [p < 0.001] and -0.24 [p < 0.001], respectively). For every 1 SD increase in PWV (2.5 m/s), FEV(1) decreased by 195.2 +/- 50.1 ml (p < 0.001) in an age- and height-adjusted analysis. The corresponding decrease in FVC was 190.4 +/- 55.0 ml (p < 0.001). Further adjustment for cardiovascular risk factors (weight, smoking habits, hypercholesterolemia, diabetes, and hypertension) did not markedly alter these results. In addition, negative associations of PWV with lung function measurements were observed within each category of cardiovascular risk factors. This study suggests that reduced pulmonary function is independently associated with aortic stiffness in men. The interrelations between pulmonary and vascular alterations should be thoroughly investigated.

Pulse pressure and heart rate: independent risk factors for cancer?

In the present study, the roles of heart rate (HR) and pulse pressure (PP) on cancer mortality, after taking into account physical activity, cigarette smoking, alcohol consumption and other confounding factors or underlying disease, were examined in men. The study included 125,513 men aged 20 to 95 years who had a health check-up at the IPC Center between 1978 and 1988. HR and PP were classified into three groups: < 60, 60-80, > 80 bpm for HR and < 50, 51-64, > or = 65 mmHg for PP. Adjusted risk ratios related to the increment from one class of HR or PP to the next for all cancer mortality were 1.4 (1.2-1.5) and 1.3 (1.1-1.4), respectively. This relationship was independent of several known risk and confounding factors, especially cigarette smoking and physical activity, and could not be explained by the presence of underlying disease.

Combined effects of heart rate and pulse pressure on cardiovascular mortality according to age.

OBJECTIVES: The aim of the study was to assess the combined effects of pulse pressure (PP) and heart rate (HR) on cardiovascular mortality in a large French population. DESIGN: The study population was composed of 125,513 men and 96,301 women aged 16-95 years who had a health check-up at the IPC Center between January 1978 and December 1988. Subjects taking antihypertensive treatment were excluded. Mortality was assessed for an 8-year period. HR and PP were classified into three groups. HR groups were: < 60, 60-79 and > or = 80 beats per minute (bpm). PP groups were: < 50, 50-64 and > or = 65 mmHg. RESULTS: In men, PP and HR were both positively associated with cardiovascular mortality risk. In women, mean arterial pressure (MAP) but not PP or HR was associated with cardiovascular mortality. In men, a combined elevation of PP and HR was associated with an important increase of cardiovascular mortality risk. The group with the highest PP and the highest HR had a 4.8-fold increase in cardiovascular mortality risk as compared to the reference group (PP < 50 mmHg and HR < 60 bpm). This effect was more pronounced in younger men (5.4-fold increase) than in older men (3.7-fold increase), as compared to the reference groups of the same age. In women, the combined effects of PP and HR on cardiovascular mortality were not significant. CONCLUSION: A combined elevation of the two components of pulsatile arterial stress is associated with an important increase in cardiovascular mortality in men, especially in younger men. In women, steady-state stress (evaluated primarily by MAP), but not pulsatile stress, is an important determinant of cardiovascular mortality.

Cardiovascular mortality in hypertensive men according to presence of associated risk factors.

To evaluate the risk of cardiovascular disease (CVD) mortality in hypertensive men according to the presence of associated risk factors (ARFs). The population was composed of 29 640 normotensive men without ARFs (reference group) and 60 343 hypertensive men (with and without ARFs) who had a standard health checkup at the Centre d'Investigations Préventives et Cliniques between 1978 and 1988. Mortality data for a mean period of 14 years were analyzed. The following ARFs were considered: total cholesterol >/=2.5 g/L, personal history of diabetes, smoking (current smokers), body mass index >28 kg/m(2), and heart rate >80 bpm. CVD risk related to the presence of isolated hypertension (assessed in hypertensive subjects without ARFs versus the reference group) increased linearly from 15% at the age of 30 years to 134% at the age of 80 years. In hypertensive subjects, one additional ARF increased CVD risk by 56% (47% to 65%, P<0.01) in younger subjects but only by 4% (-8% to 17%, P=NS) in older subjects. The role of hypercholesterolemia and tobacco smoking in CVD mortality was significantly higher in hypertensive subjects aged <55 years than in hypertensive subjects aged >/=55 years (P<0.01), whereas the roles of tachycardia and obesity were not affected by age. In younger hypertensive subjects, evaluation of CVD risk and therapeutic strategies should target ARFS: In older subjects, the presence of high blood pressure levels seems to be the major determinant of CVD risk.

Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity.

Chronological age is the primary determinant of stiffness of central arteries. Increased stiffness is an independent indicator of cardiovascular risk. The aim of this study was to determine whether telomere length, a possible index of biological aging, provides a better account than chronological age for variation in arterial stiffness, evaluated by measuring pulse pressure and aortic pulse wave velocity. The study population included 193 French subjects (120 men, 73 women), with a mean age of 56+/-11 years, who were not on any antihypertensive medications. Telomere length was evaluated in white blood cells by measuring the mean length of the terminal restriction fragments. Age-adjusted telomere length was longer in women than in men (8.67+/-0.09 versus 8.37+/-0.07 kb; P=0.016). In both genders, telomere length was inversely correlated with age (P<0.01). Multivariate analysis showed that in men, but not in women, telomere length significantly contributed to pulse pressure and pulse wave velocity variations. In conclusion, telomere length provides an additional account to chronological age of variations in both pulse pressure and pulse wave velocity among men, such that men with shorter telomere length are more likely to exhibit high pulse pressure and pulse wave velocity, which are indices of large artery stiffness. The longer telomere length in women suggests that for a given chronological age, biological aging of men is more advanced than that of women.

Should diastolic and systolic blood pressure be considered for cardiovascular risk evaluation: a study in middle-aged men and women.

OBJECTIVES: The goal of this study was to evaluate the role of diastolic blood pressure (DBP) in cardiovascular mortality for different systolic blood pressure (SBP) levels in middle-aged men and women. BACKGROUND: In middle-aged subjects it is unclear whether DBP, in addition to SBP, should be considered for risk evaluation. METHODS: Subjects (77,023 men; 48,480 women) aged 40 to 70 years old, had no major cardiovascular disease, no antihypertensive treatment and were examined at the Centre d'Investigations Preventives et Cliniques between 1972 and 1988. Mortality was assessed for an 8- to 12-year period. RESULTS: In both genders, cardiovascular mortality increased with the SBP level. In men and women with normal SBP levels, DBP did not influence cardiovascular mortality after adjustment for age and SBP. In men with systolic hypertension, a U-shaped curve relationship between cardiovascular mortality and DBP was observed, with the lowest mortality rates in the group with DBP 90 to 99 mm Hg. Compared with this group, age- and SBP-adjusted cardiovascular mortality was higher by 73% (p < 0.02) in the group with DBP <90 mm Hg and by 65% (p < 0.001) in the group with DBP > or =110 mm Hg. In women with systolic hypertension, however, DBP was positively correlated with cardiovascular mortality. CONCLUSIONS: In middle-aged subjects, classification of cardiovascular risk according to DBP levels should take into account gender, especially when SBP levels are elevated. Men with systolic hypertension are at higher risk when their DBP is "normal" than when they present a mild to moderate increase in DBP. In women of the same age, however, systolic-diastolic hypertension represents a higher risk than isolated systolic hypertension.

How can hypertensive patients be better treated? The contribution of combination therapy.

Recent studies demonstrated that target blood pressure (BP) in treated hypertensive patients should be below 140 mmHg for systolic blood pressure (SBP) and below 90 mmHg for diastolic blood pressure (DBP). However, population studies from several countries have demonstrated that in clinical practice the proportion of controlled hypertensive patients is less than 30%. In order to elucidate these questions in France we analysed a large population of 145,000 subjects examined at the Centre d'Investigations Préventives et Cliniques in Paris (IPC). Among those with high BP at the time of their IPC visit, only 20% received an antihypertensive treatment. Among those receiving an antihypertensive treatment, less than 27% (24% in men and 30% in women) presented with BP values less than 140 mmHg for SBP and less than 90 mmHg for DBP. This analysis also showed that 72% of hypertensive patients presented with at least one modifiable associated cardiovascular risk factor and that more than 30% of hypertensive men and more than 25% of hypertensive women presented with at least two associated risk factors. The use of combination therapies could help to increase the percentage of well-controlled hypertensive subjects. It has been shown that in order to reach this BP level, combination therapy should be used in more than two-thirds of the treated subjects. The trandolapril-verapamil combination is the first fixed combination of an angiotensin-converting enzyme inhibitor and a non-dihydropyridine calcium-channel blocker. Administered once daily, this combination reduces BP more than a classic monotherapy. The effects of the trandolapril-verapamil combination on risk factors are either neutral (metabolic parameters), or even beneficial (reduction in heart rate).

LRDD, a novel leucine rich repeat and death domain containing protein.

Death domains (DD) and leucine rich repeats (LRR) are two different types of protein interaction motifs. Death domains are found predominantly in proteins involved in signaling and are involved in homo- and heteromultimerization. Leucine rich repeats are found in proteins with diverse cellular functions, like cell adhesion and cellular signaling, and mediate reversible protein-protein interactions. In this paper we report the cloning of a new human gene called LRDD (leucine repeat death domain containing protein). LRDD encodes a protein of 83 kDa with six LRRs at the N-terminus and a DD at the C-terminus. LRDD appears to be processed into two fragments of about 33 and 55 kDa, containing LRRs and DD respectively. Interestingly, LRDD is shown to interact with two other death domain containing proteins, FADD and MADD, presumably through death domain interactions. LRDD may represent a new type of adapter protein that could be involved in signaling or other cellular functions.