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Background Left ventricular (LV) function depends on the activity of transmembrane electrolyte transporters. Failing human myocardium has lower Na+/K+ ATPase expression and higher intracellular sodium concentrations. The ATP12A gene encodes a catalytic subunit of an ATPase that can function as a Na+/K+ pump. We, therefore, investigated the association between LV function and common genetic variants in ATP12A. Methods A random sample of 1166 participants (53.7% women; mean age 49.5 years, 44.8% hypertensive) was recruited in Belgium, Poland, Italy and Russia. We measured transmitral early and late diastolic velocities (E and A) by pulsed wave Doppler, and mitral annular velocities (e' and a') by tissue Doppler. Using principal component analysis, we summarized 7 Doppler indexes - namely, E, A, e' and a' velocities, and their ratios (E/A, e'/a', and E/e') - into a single diastolic score. We genotyped 5 tag SNPs (rs963984, rs9553395, rs10507337, rs12872010, rs2071490) in ATP12A. In our analysis we focused on rs10507337 because it is located within a transcription factor binding site. Results In the population-based analyses while adjusting for covariables and accounting for family clusters and country, rs10507337 C allele carriers had significantly higher E/A (P = 0.003), e' (P = 5.8x10-5), e'/a' (P = 0.003) and diastolic score (P = 0.0001) compared to TT homozygotes. Our findings were confirmed in the haplotype analysis and in the family-based analyses in 74 informative offspring. Conclusions LV diastolic function as assessed by conventional and tissue Doppler indexes including a composite diastolic score was associated with genetic variation in ATP12A. Further experimental studies are necessary to clarify the role of ATP12A in myocardial relaxation. [ABSTRACT FROM AUTHOR]

Experts proposed blood pressure (BP) load derived from 24-hour ambulatory BP recordings as a more accurate predictor of outcome than level, in particular in normotensive people. We analyzed 8711 subjects (mean age, 54.8 years; 47.0% women) randomly recruited from 10 populations. We expressed BP load as percentage (%) of systolic/ diastolic readings ≥135/≥85 mmHg and ≥120/≥70 mmHg during day and night, respectively, or as the area under the BP curve (mmHgxh) using the same ceiling values. During a period of 10.7 years (median), 1284 participants died and 1109 experienced a fatal or nonfatal cardiovascular end point. In multivariable-adjusted models, the risk of cardiovascular complications gradually increased across deciles of BP level and load (P<0.001), but BP load did not substantially refine risk prediction based on 24-hour systolic or diastolic BP level (generalized R2 statistic ≤0.294%; net reclassification improvement ≤0.28%; integrated discrimination improvement ≤0.001%). Systolic/diastolic BP load of 40.0/42.3% or 91.8/73.6 mmHgxh conferred a 10-year risk of a composite cardiovascular end point similar to a 24-hour systolic/diastolic BP of 130/80 mmHg. In analyses dichotomized according to these thresholds, increased BP load did not refine risk prediction in the whole study population (R²≤0.051) or in untreated participants with 24-hour ambulatory normotension (R²≤0.034). In conclusion, BP load does not improve risk stratification based on 24-hour BP level. This also applies to subjects with normal 24-hour BP for whom BP load was proposed to be particularly useful in risk stratification. [ABSTRACT FROM AUTHOR]

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Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24-hour ambulatory PP, we analyzed 9938 participants randomly recruited from 11 populations (47.3% women). After age stratification (<60 versus ≥60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (HRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mmHg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68 853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top PP tenth (mean, 60.6 mmHg). Using stepwise increasing PP levels, the lower boundary of the 95% confidence interval of the successive thresholds did not cross unity. Among 3910 older participants (39923 person-years), risk increased (P≤0.028) in the top PP tenth (mean, 76.1 mmHg). HRs were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69, and 1.40 for all cardiovascular, cardiac, and cerebrovascular events. The lower boundary of the 95% confidence interval of the HRs associated with stepwise increasing PP levels crossed unity at 64 mm Hg. While accounting for all covariables, the top tenth of PP contributed less than 0.3% (generalized R² statistic) to the overall risk among the elderly. Thus, in randomly recruited people, ambulatory PP does not add to risk stratification below age 60; in the elderly, PP is a weak risk factor with levels below 64 mmHg probably being innocuous. [ABSTRACT FROM AUTHOR]

BACKGROUND The general belief that orthostatic hypotension (OH) predisposes to cardiovascular events is based on sparse and contradictory data, rarely derived from population studies. METHODS A total of 1,016 men and women aged ≥65 years was studied in a 12-year epidemiological population-based study. Cardiovascular events were detected in subjects with and without OH (blood pressure (BP) decrease ≥20mm Hg for systolic or ≥10mm Hg for diastolic), and Cox analysis was performed including OH as an independent variable. RESULTS In univariate analysis, coronary (20.2% vs. 13.1%, P = 0.05), cerebrovascular (13.1% vs. 8.4%, P = 0.05), and heart failure (HF) events (20.2% vs. 13.8%, P = 0.03) were apparently more incidental in subjects with OH than in those without OH. Nevertheless, after adjusting for age, gender, and systolic BP as confounders, OH did not act as a cardiovascular predictor (relative risk for cerebrovascular events 1.33, 95% confidence interval (CI), 0.78–2.2, for coronary events 1.25, CI 0.82–1.88, for HF 1.07, CI 0.71–1.62, for arrhythmias 0.82, CI 0.40–1.37, and for syncope 0.58, CI 0.13–2.71). CONCLUSIONS Although OH seems to be a predictor of coronary, cerebrovascular, and HF events, no predictive role was found in models that include biological confounders. Independent of the cause of OH, age and systolic BP, which are positively associated with OH, fully explain the greater incidence of cardiovascular events and the greater cardiovascular risk observed in subjects with OH. [ABSTRACT FROM AUTHOR]

BACKGROUND Average real variability (ARV) is a recently proposed index for short-term blood pressure (BP) variability. We aimed to determine the minimum number of BP readings required to compute ARV without loss of prognostic information. METHODS ARV was calculated from a discovery dataset that included 24-hour ambulatory BP measurements for 1,254 residents (mean age = 56.6 years; 43.5% women) of Copenhagen, Denmark. Concordance between ARV from full (≥80 BP readings) and randomly reduced 24-hour BP recordings was examined, as was prognostic accuracy. A test dataset that included 5,353 subjects (mean age = 54.0 years; 45.6% women) with at least 48 BP measurements from 11 randomly recruited population cohorts was used to validate the results. RESULTS In the discovery dataset, a minimum of 48 BP readings allowed an accurate assessment of the association between cardiovascular risk and ARV. In the test dataset, over 10.2 years (median), 806 participants died (335 cardiovascular deaths, 206 cardiac deaths) and 696 experienced a major fatal or nonfatal cardiovascular event. Standardized multivariable-adjusted hazard ratios (HRs) were computed for associations between outcome and BP variability. Higher diastolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.19), and cardiac (HR = 1.19) mortality and fatal combined with nonfatal cerebrovascular events (HR = 1.16). Higher systolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.17), and cardiac (HR = 1.24) mortality. CONCLUSIONS Forty-eight BP readings over 24 hours were observed to be adequate to compute ARV without meaningful loss of prognostic information. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: This research was aimed at clarifying whether high dietary fiber intake has an impact on incidence and risk of stroke at a population level. Methods: In 1647 unselected subjects, dietary fiber intake (DFI) was detected in a 12-year population-based study, using other dietary variables, anagraphics, biometrics, blood pressure, heart rate, blood lipids, glucose, insulin, uricaemia, fibrinogenaemia, erytrosedimentation rate, diabetes, insulin resistance, smoking, pulmonary disease and left ventricular hypertrophy as covariables. Results: In adjusted Cox models, high DFI reduced the risk of stroke. In analysis based on quintiles of fiber intake adjusted for confounders, HR for incidence of stroke was lower when the daily intake of soluble fiber was >25 g or that of insoluble fiber was >47 g. In multivariate analyses, using these values as cut-off of DFI, the risk of stroke was lower in those intaking more that the cut-off of soluble (HR 0.31, 0.17–0.55) or insoluble (HR 0.35, 0.19–0.63) fiber. Incidence of stroke was also lower (−50%, p < 0.003 and −46%, p < 0.01, respectively). Conclusions: Higher dietary DFI is inversely and independently associated to incidence and risk of stroke in general population. [Copyright &y& Elsevier]

BACKGROUND The double product (DP), consisting of the systolic blood pressure (SBP) multiplied by the pulse rate (PR), is an index of myocardial oxygen consumption, but its prognostic value in the general population remains unknown. METHODS We recorded health outcomes in 9,937 subjects (median age, 53.2 years; 47.3% women) randomly recruited from 11 populations and enrolled in the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcomes (IDACO) study. We obtained the SBP, PR, and DP for these subjects as determined through 24-hour ambulatory monitoring. RESULTS Over a median period of 11.0 years, 1,388 of the 9,937 study subjects died, of whom 536 and 794, respectively, died of cardiovascular (CV) and non-CV causes, and a further 1,161, 658, 494, and 465 subjects, respectively, experienced a CV, cardiac, coronary, or cerebrovascular event. In multivariate-adjusted Cox models, not including SBP and PR, DP predicted total, CV, and non-CV mortality (standardized hazard ratio [HR], ≥ 1.10; P ≤ 0.02), and all CV, cardiac, coronary, and stroke events (HR, ≥ 1.21; P < 0.0001). For CV mortality (HR, 1.34 vs. 1.30; P = 0.71) and coronary events (1.28 vs. 1.21; P = 0.26), SBP and the DP were equally predictive. As compared with DP, SBP was a stronger predictor of all CV events (1.39 vs. 1.27; P = 0.002) and stroke (1.61 vs. 1.36; P < 0.0001), and a slightly stronger predictor of cardiac events (1.32 vs. 1.22; P = 0.06). In fully adjusted models, including both SBP and PR, the predictive value of DP disappeared for fatal endpoints (P ≥ 0.07), coronary events (P = 0.06), and stroke (P = 0.12), or DP was even inversely associated with the risk of all CV and cardiac events (both P ≤ 0.01). CONCLUSION In the general population, we did not observe DP to add to risk stratification over and beyond SBP and PR. [ABSTRACT FROM AUTHOR]

To verify whether the C825T polymorphism of the GNB3 influences the response to neuropsychological tests, mini-mental state examination, digit span (DS), immediate and delayed prose memory, memory with interference at 10 and 30 seconds (MI 10 and 30), trail making tests (TMTs) A and B, abstraction task, verbal fluency (VF) test, figure drawing and copying, overlapping figures test and clock testwere performed in 220 elderlymen andwomen free fromclinical dementia and fromneurological and psychiatric diseases randomly taken from the Italian general population and analysed across the C825T polymorphism.The performance of DS, immediate and delayed prosememory, VF, and TMTs was worse in subjects who were TT for the polymorphism in comparison to the C-carriers.The performance of all tests declined with age. In the case of DS, immediate and delayed prose memory, MI 10 and VF, this trend wasmaintained in the C-carriers but not in TT. In the case of prosememory, ofmemory with interference, and of VF, schooling reduced the detrimental interaction between age and genotype. The C825T polymorphism of GNB3 gene therefore influences memory and verbal fluency, being additive to the effects of age and partially mitigated by schooling. [ABSTRACT FROM AUTHOR]

The efficacy of hypnotic suggestion of high performance was evaluated in 10 young healthy volunteers undergoing isometric exercise (hand grip) in basal conditions of usual normal consciousness and in profound hypnosis. To this aim, they were asked to perform dynamometric hand grip at maximal muscular strength and for the longest time compatible with individual tolerance. As a specific suggestion, a hallucination of drinking an 'energizing potion' capable of increasing muscular performance and abolishing the sense of fatigue and pain associated with isometric exercise was induced. Haemodynamic parameters were continuously measured. In comparison to basal conditions of usual consciousness, the exercise performer under hypnotic suggestion was associated with a 12% increase in maximal muscular strength and a 60% increase in exercise length. A greater increase of heart rate, arterial blood pressure, and double product-accompanied by a lower increase of stroke voLume and consequently of cardiac index-was recorded. Nevertheless, exercise-induced vasodilation was comparable in the two conditions, so that the increase in cardiac index observed during hypnotic suggestion was entirely sustained by heart rate increase. Such a condition can only be tolerated for a short time and at the expense of a reduced myocardial (particularly subendocardic) perfusion. It seems therefore that the hypnotic command 'perform over your natural limits' is followed by an increase in strength but particularly in exercise length. In such conditions, physical performance is actually greater than that achieved in normal conditions, as if the subject was able to draw on energies not usually employed in everyday life. This higher performance is unnatural and is sustained by muscular mechanisms activating unfavourable, and potentially dangerous, haemodynamic reflexes. Although hypnosis is a formidable tool in the study of human physiology, its use in the physical world (particularly sporting activities) should be limited to specific controlled con- ditions. In fact, by increasing muscular power and decreasing the sense of fatigue, hypnosis seems to be able to deprive subjects of the natural feedback mechanisms well-synthesized in the sentences 'It's too much for me' or 'I can't take it any more'. [ABSTRACT FROM AUTHOR]

After rapid hypnotic induction, 12 healthy volunteers underwent hypnotic deepening with relaxation or with fractionation (without relaxation) in a random latin-square protocol. Electroencephalographic occipital alpha activity was measured, low-resolution brain electromagnetic tomography was performed, and hemodynamics (stroke volume, heart rate, cardiac output, mean arterial blood pressure, forearm arterial flow and resistance) were monitored in basal conditions and after deepening. After relaxation, both forearm flow (−18%) and blood pressure (−4%) decreased; forearm resistance remained unchanged. After fractionation, a forearm flow decrease comparable to that recorded after relaxation was observed, but blood pressure remained unchanged, leading to an increase of forearm resistance (+51%). Central hemodynamics did not change. Alpha activity increased in the precuneus after fractionation only. In conclusion, both relaxation and fractionation have vasoconstrictor effects, but fractionation is also associated with an increase in peripheral resistance. [ABSTRACT FROM PUBLISHER]

BackgroundThe role of C825T polymorphism of the candidate GNB3 gene in predicting cerebrovascular outcome has been poorly explored in longitudinal setting at a population level.MethodsIn an epidemiological setting, 1,678 men and women from general population were genotyped for C825T polymorphism of GNB3 gene and follow-up for 10 years to detect nonfatal and fatal cerebrovascular events (CE). Established cerebrovascular risk factors were used to adjust the multivariate Cox analysis for confounders.ResultsSeventy-three nonfatal and 30 fatal CE were recorded. Incidence of CE was higher in TT than in C-carriers (fatal: 2.6 vs. 1.7%, P < 0.03; nonfatal: 7.8 vs. 3.9%, P < 0.03; fatal recurrences: 1.6 vs. 0.6%, P < 0.03). In Cox analysis, the TT genotype predicted nonfatal (hazard ratio 1.99, 95% confidence interval 1.05-3.79, P = 0.03), fatal (2.91, 1.05-8.12, P = 0.04), and fatal recurrent CE (6.82, 1.50-31.1, P = 0.02) also after adjustment for age, gender, systolic and diastolic blood pressure, body adiposity, atherogenetic blood lipids, serum uric acid, diabetes, calories, caffeine and ethanol intake, and coronary events at baseline. Further adjustment for historical CE made the association between TT genotype and incident fatal CE nonsignificant (hazard ratio 2.72, 95% confidence interval 0.96-7.22, P = 0.06).ConclusionsThe TT genotype of GNB3 gene predicts incident CE independent of blood pressure and other established risk factors at a population level. Further studies are needed to clarify the nature and pathways of this association.American Journal of Hypertension (2012). doi:10.1038/ajh.2011.257 [ABSTRACT FROM AUTHOR]

The article discusses the study that analyzed subjects from the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes to determine the significance of white-coat hypertension in isolated systolic hypertension subjects. The subjects with white-coat hypertension are presented to have higher risks for a cardiovascular event. A term treated normalized hypertension is cited to be given to those receiving antihypertensive treatment.

Background. As arteries become stiffer with ageing, reflected waves move faster and augment late systolic pressure. We investigated the age dependency of peripheral and central systolic pressure, pressure amplification (peripheral systolic blood pressure − central systolic blood pressure), and peripheral and central systolic augmentation (maximal systolic pressure minus the first peak of the pressure wave). Methods. We randomly recruited 1420 White Europeans (mean age, 41.7 years). peripheral systolic blood pressure and central systolic blood pressure were measured by means of an oscillometric sphygmomanometer and pulse wave analysis, respectively. Results. In cross-sectional analyses (731 women, 689 men), central systolic blood pressure and central systolic augmentation increased more with age than peripheral systolic blood pressure and peripheral systolic augmentation. These age-related increases were greater in women than men. The age-related decrease in pressure amplification was similar in both sexes. In longitudinal analyses (208 women, 190 men), the annual increases in central systolic blood pressure and central systolic augmentation were steeper ( p < 0.001) than those in peripheral systolic blood pressure and peripheral systolic augmentation with no sex differences ( p ≥ 0.068), except for peripheral systolic augmentation, which was larger in women ( p = 0.002). Longitudinally, pressure amplification decreased more with age in women than men ( p = 0.012). In multivariable-adjusted analyses, age was the overriding determinant of peripheral systolic blood pressure and central systolic blood pressure. Conclusion. With ageing, peripheral systolic blood pressure approximates to central systolic blood pressure. This might explain why in older subjects peripheral systolic blood pressure becomes the main predictor of cardiovascular complications. [ABSTRACT FROM AUTHOR]

Previous studies on the prognostic significance of the morning blood pressure surge (MS) produced inconsistent results. Using the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome, we analyzed 5645 subjects (mean age: 53.0 years; 54.0% women) randomly recruited in 8 countries. The sleep-through and the preawakening MS were the differences in the morning blood pressure with the lowest nighttime blood pressure and the preawakening blood pressure, respectively. We computed multivariable-adjusted hazard ratios comparing the risk in ethnic- and sex-specific deciles of the MS relative to the average risk in the whole study population. During follow-up (median: 11.4 years), 785 deaths and 611 fatal and nonfatal cardiovascular events occurred. While accounting for covariables and the night:day ratio of systolic pressure, the hazard ratio of all-cause mortality was 1.32 (95% CI: 1.09 to 1.59; P=0.004) in the top decile of the systolic sleep-through MS (>or=37.0 mm Hg). For cardiovascular and noncardiovascular death, these hazard ratios were 1.18 (95% CI: 0.87 to 1.61; P=0.30) and 1.42 (95% CI: 1.11 to 1.80; P=0.005). For all cardiovascular, cardiac, coronary, and cerebrovascular events, the hazard ratios in the top decile of the systolic sleep-through MS were 1.30 (95% CI: 1.06 to 1.60; P=0.01), 1.52 (95% CI: 1.15 to 2.00; P=0.004), 1.45 (95% CI: 1.04 to 2.03; P=0.03), and 0.95 (95% CI: 0.68 to 1.32; P=0.74), respectively. Analysis of the preawakening systolic MS and the diastolic MS generated consistent results. In conclusion, a MS above the 90th percentile significantly and independently predicted cardiovascular outcome and might contribute to risk stratification by ambulatory blood pressure monitoring. [ABSTRACT FROM AUTHOR]

Summary: Stroke is the second most common cause of death worldwide and is the complication of hypertension that is most directly linked to blood pressure. Hypertension affects nearly 30% of the world''s population; therefore, reducing blood pressure is key for the prevention of stroke. Unlike the established role of hypertension as a risk factor for stroke, the prognostic importance of blood pressure in determining outcome after acute stroke is unclear. The acute hypertensive response occurs in more than 50% of all patients with acute stroke and is associated with poor prognosis. The relation between the outcome of acute stroke and blood pressure is U-shaped, with the best outcome at systolic blood-pressure levels ranging from about 140 to 180 mm Hg. The evidence that decreasing blood pressure in hypertensive patients with acute ischaemic or haemorrhagic stroke improves prognosis needs further confirmation. Whether raising blood pressure to improve perfusion of ischaemic brain areas is beneficial remains even more uncertain. Present guidelines for the management of blood pressure in patients with acute stroke are not evidence-based, but results from ongoing trials might provide more informed recommendations for the future. [Copyright &y& Elsevier]

High systolic blood pressure represents a challenge for the modern world. Epidemiologists are in the best position to appreciate the importance of systolic hypertension and its cardiovascular consequences. Although the label of hypertension seems to have lower importance in the elderly, and above all in the very old, than in younger people, high systolic and high pulse pressure are risk factors for cardiovascular events and necessitates treatment. Unfortunately, due to indolence and lack of aggressiveness, only a limited fraction of elderly hypertensive patients receives adequate therapy. [ABSTRACT FROM AUTHOR]

Cardiovascular disease remains the leading cause of death worldwide. In this review, we briefly summarize new insights on the modulation of genetic cardiovascular risk by host factors such as sex and age and lifestyle factors such as salt intake. As phenotypes (genotypes) of interest, we considered left ventricular structure and function (ADD1 Gly460Trp; AGTR2 G1675A; ACE D/I), the incidence of heart failure (ADD1 Gly460Trp), heart rate variability (CYP11B2 C-344T; AGTR1 A1166C), carotid distensibility (IL6 G-174C), and serum lipid levels (APOE ɛ 2/ ɛ 3/ ɛ 4; APOA1 A 75G). In each case, the associations with the genetic cardiovascular risk factor were modulated by sex, age, sodium intake, or a combination thereof. These interactions highlight that genetic risk factors and phenotype-genotype associations can only be interpreted within their ecogenetic context. Perhaps a better understanding of these phenomena will lead researchers to target in a more specific way the pathophysiologic mechanisms operating within each individual. [ABSTRACT FROM AUTHOR]

Background: The role of body mass index (BMI) as a factor influencing longevity of the elderly subject is still under debate. Objective: To evaluate at a population level whether or not BMI is a risk factor of mortality in the elderly, highlighting possible gender-related differences. Methods: 3,282 subjects aged 65–95 years, were recruited from an Italian general population and 12-year events were recorded. Blood tests and anthropometric measurements were performed. BMI as a continuous item was divided into quintiles and, for each quintile, adjusted hazard ratio (HR) with 95% confidence intervals for mortality was derived by classes of age and gender from Cox analysis. Results: BMI inversely predicted overall and cancer mortality in men only. Overall mortality rate was 64.7% (HR = 1.63 [1.23–2.71]) in the 1st quintile of BMI, 54.9% (1.21 [0.92–1.73]) in the 2nd, 54.1% (1.20 [0.85–1.67]) in the 3rd, 53.3% (1.04 [0.82–1.32]) in the 4th and 52.5% in the 5th; cancer mortality rate was 23.1% (HR = 2.35 [1.31–4.23]), 14.2% (HR = 1.19 [0.65–1.80]), 15.8% (HR = 1.49 [0.93–2.39]), 15.8% (HR = 1.36 [0.84–2.16]) and 13.4%, respectively. The relationship between BMI and mortality remained significant only in men aged 76 years or less. No relationship was found between BMI and coronary or cerebrovascular mortality. Conclusions: BMI <22.7 kg/m2 does not improve survival in the elderly, while it is an independent predictor of cancer mortality in men aged ≤76 years. No prediction based on BMI is possible in women. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate risk pattern and mortality in a general population epidemiologic study performed by a staff of hypertension specialists working as the "good father of a family," with lifestyle and therapeutic advice and instrumental measurements. Mortality among the study population (n=856) during the 4-y study was compared with that recorded in the general population during the 4-y period before the study; those who refused to participate in the study were also recorded (n=280). Among study subjects, blood pressure decreased by 3.6/3.5 mm Hg (P<.01/P<.0001), serum total cholesterol by 3.8% (P<.0001), and low-density lipoprotein cholesterol by 10.9% (P<.01); awareness of hypertension increased by 87% (P<.0001); 20% of hypercholesterolemic patients (P<.01) and 28% of diabetic patients (P<.001) were identified; and 40% of hypertensive patients (P<.0001) were treated. Overall 4-y mortality was 12.5% in study subjects, 36.6% in renitent subjects (P<.0001 vs enrolled), and 19.9% during the period preceding the study (P<.0001 vs enrolled); cardiovascular mortality rates were 5.8%, 18.6% (P<.0001), and 11.4% (P<.0001), respectively. In particular, the frequency of fatal stroke was 0.06%, 3.8% (P<.0001), and 2.5% (P<.0001), respectively, and that of fatal coronary events was 3.4%, 7.5% (P<.0001), and 4.6% (P<.0001), respectively. In conclusion, when an epidemiologic professional staff member approaches patients in a manner similar to that of the "good father of a family," a better risk pattern and lower mortality rates (particularly cerebrovascular and coronary) are seen in those who are receptive to the care provided; those who decide not to participate in health care opportunities do not benefit. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of low-density lipoprotein cholesterol (LDL-C) as a predictor of mortality in elderly subjects. Design: Population-based prospective cohort study. Setting: Two communities in northern Italy. Participants: Three thousand one hundred twenty Caucasian subjects aged 65 and older recruited in for the Cardiovascular Study in the Elderly and followed up for 12 years. Measurements: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL-C, glucose, creatinine, and body mass index. Clinical measures: medical assessment, diabetes mellitus, hypertension, stroke, coronary disease, heart failure, and smoking and drinking habits. Vital status measures: death certificates from the Registry Office and causes of death according to the International Classification of Diseases. After plotting mortality rates using quartiles of LDL-C, relative hazard rates (RHRs) were calculated using multivariate Cox regression analyses. When the trend was nonlinear, the RHRs were further calculated for the 25th, 50th, and 75th percentiles of the distribution to confirm curvilinearity. Results: The distribution of risk of total mortality in women and of fatal heart failure in all subjects was curvilinear (non J-shaped), decreasing nonlinearly with LDL-C. For total mortality in men and cardiovascular mortality in both sexes, the relationship with LDL-C was J-shaped. The risk of fatal myocardial infarction was J-shaped in men, whereas it increased linearly with higher LDL-C in women. In both sexes, the association between stroke mortality and LDL-C was not significant. Conclusion: This study adds to the uncertainty of the role of elevated levels of LDL-C as a risk factor for mortality in old people. [ABSTRACT FROM AUTHOR]

Manidipine and lercanidipine are considered effective and safe in the treatment of chronic arterial hypertension and are equipotent in reducing blood pressure (BP) levels. Their main side effect is ankle-foot edema. After a 2-week placebo run-in period, these 2 drugs were compared in a controlled parallel-group study lasting 3 months, involving 53 patients with mild-to-moderate essential hypertension (26 assigned to manidipine and 27 to lercanidipine). At the end of the active treatment period, BP was significantly reduced in comparison with the end of the placebo phase in both the manidipine and the lercanidipine groups, without significant differences between the 2 drugs. Daytime BP was significantly reduced by 5.5%/5.6% with manidipine and by 3.8%/6.6% with lercanidipine, while smaller reductions were seen at nighttime. The smoothness index was the same with both drugs. Unlike lercanidipine, manidipine significantly reduced both basal (-30%) and minimal vascular resistance (-39%), qualifying it as a potent vasodilator. Despite vasodilation, heart rate was not increased but was even slightly reduced by treatment. Ankle-foot edema was observed with both drugs but was less pronounced with manidipine, probably because of greater postcapillary dilatation. In conclusion, manidipine and lercanidipine are both effective and safe in mild-to-moderate essential hypertension, although the former seems to have a more favorable tolerability profile than the latter. [ABSTRACT FROM AUTHOR]

The associations of the β-adducin C1797T polymorphism with blood pressure (BP) and various indexes of sodium homeostasis were investigated in 388 men and 456 women, aged 18 to 60 years, recruited from three European populations (Cracow, Poland, n = 300; Novosibirsk, Russian Federation, n = 274; Mirano, Italy; n = 270). Phenotypes included 24-h ambulatory BP and urinary excretion of electrolytes and aldosterone. Subjects were genotyped for the β-adducin polymorphism. Both a population-based association study and a family-based analysis were performed. Urinary sodium excretion was higher in Cracow than in Mirano (241 v 185 mmol/24 h, P < .05) and intermediate in Novosibirsk (206 mmol/24 h). The β-adducin T allele (15.2% v 9.1%, P < .0001) was more prevalent in Mirano than in the two Slavic centers. In both population-based and family-based association analyses, there was significant heterogeneity between Slavic and Italian subjects in the phenotype–genotype relationships with β-adducin. In the Slavic centers, 24-h systolic BP was higher in T allele carriers than in CC homozygotes (122.3 v 119.7 mm Hg, P = .03), whereas this was not the case in Mirano (121.8 v 122.9 mm Hg, P = .42). In Slavic (212.6 v 233.1 mmol/24 h) as well as in Italian (166.1 v 191.5 mmol/24 h) participants, 24-h sodium excretion was lower (P = .01) in T allele carriers than in CC homozygotes. These results were confirmed in the family-based analysis of offspring using a quantitative transmission disequilibrium test. In conclusion, the frequency of the β-adducin T allele and salt intake differ across European populations. Thus, both variation in genetic background and salt intake may explain the observed heterogeneity in the phenotype–genotype relationships. Genetic determinants of complex quantitative traits such as BP can only be investigated within their epidemiologic context. [Copyright &y& Elsevier]