Dosimetric study to assess the feasibility of intraoperative radiotherapy with electrons (ELIOT) as partial breast irradiation for patients with cardiac implantable electronic device (CIED).

PURPOSE: To report in-vivo dosimetry in the infraclavicular region, a potential site of a cardiac implantable electronic device (CIED) and to evaluate the absorbed dose from intraoperative radiotherapy with electrons (ELIOT). METHODS: 27 non-cardiopathic breast cancer (BC) patients without CIED received quadrantectomy and ELIOT as partial breast irradiation. Before delivering ELIOT, two catheters, each containing eight thermoluminescent dosimeters (TLDs), were positioned in the infraclavicular region. TLDs internal catheter was located deep in the tumor bed while the external catheter was placed on patient's skin. RESULTS: Data were available for 24/27 patients. The absorbed doses were referred to the dose of 21 Gy. Values measured by the external catheter were low, although statistically significant higher doses were found close to the applicator (mean values 0.26-0.49 Gy). External TLD doses in proximity of the applicator were lower than those detected by their internal counterparts. Values measured by the internal catheter TLDs varied according to the distance from the applicator while no correlation with tumor site and beam energy was found. The distance from the applicator to deliver < 2 Gy to a CIED was 2 cm, while from 2.5 cm the dose measured in all the patients became negligible. CONCLUSIONS: This dosimetric study provided data to support the clinical use of ELIOT in BC patients having CIEDs as long as the suggested minimum safe distance of 2.5 cm is taken from the RT field in case of ELIOT single dose of 21 Gy, in the energy range of 6-10 MeV.

Radiotherapy in patients with cardiac implantable electronic devices: clinical and dosimetric aspects.

As a result of aging, the number of patients with cardiac implantable electronic device (CIED) requiring radiotherapy (RT) continues to rise. The aim of this work was to evaluate RT-related malfunctions of CIED in a cohort of patients who underwent RT in our clinic from June 2010 to December 2016. We retrospectively analyzed 93 RT treatments in 63 patients with CIEDs. Patients were treated with 3D conformal RT, intensity-modulated RT and stereotactic RT. We collected clinical characteristics of cancer, models of CIEDs, total RT dose to tumor and radiation energy. Radiation dose delivered to CIED and its dysfunctions after RT was evaluated. Subgroup analysis of 48 RT treatments (32 patients) on chest and neck plus on 13 RT treatments (12 patients) with 18 MV neutron-producing photon energy considered as high risk was performed. The number of treatments of patients with CIEDs increased from 0.3% in 2011 to 1.2% in 2016. Two patients, treated with 18 MV photon beam, with implantable cardioverter-defibrillators (ICDs) that received a maximum dose of around 2.1 Gy, experienced adverse events: a reprogramming of ICD when the patient reached a delivered dose to the tumor of 32 Gy, and an altered sensing function requiring replacement after 11 months from the end of RT. Nearly 2% of patients with CIEDs from high-risk patients subgroup had experienced a damage of the device. Close cooperation between radiation oncologists, cardiologists, medical physicists and radiation technologists is needed to achieve the best practice management in these patients.

Familial premature coronary artery disease mortality and obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is linked to both coronary artery disease (CAD) and sudden death, but any causal role remains unclear. A family history of premature CAD and related mortality is an independent risk factor for the development of CAD. We hypothesized that OSA is associated with a family history of premature mortality from ischemic heart disease. METHODS: We prospectively studied 588 subjects who underwent polysomnography from May 2000 to June 2004. Demographics, comorbidities, family history of cardiovascular disease, and the ages and causes of death for 10 strata of family members were recorded for all subjects. We excluded those subjects with known causes of premature cardiac death, such as hypertrophic cardiomyopathy and long-QT syndrome. OSA was defined by American Academy of Sleep Medicine criteria (ie, apnea-hypopnea index >or= 5). Premature CAD mortality was defined as death due to ischemic heart disease or sudden cardiac death before 55 years of age (men) or 65 years of age (women). RESULTS: Polysomnography confirmed OSA in 316 subjects and excluded it in 202 subjects. The unadjusted odds ratio (OR) for OSA and a family history of premature CAD mortality was 2.11 (95% confidence interval [CI], 1.10 to 4.31; p = 0.031). After adjusting for each subject's sex, body mass index, and history of CAD, there was a significant and independent association between OSA and family history of premature CAD mortality (OR, 2.13; 95% CI, 1.04 to 4.66; p = 0.046). CONCLUSIONS: Regardless of their own CAD status, people with OSA are more likely than those without OSA to have a family history of premature CAD mortality.

Validation of the SAA-102 home blood pressure monitor according to the protocols of the European Society of Hypertension, the Association for the Advancement of Medical Instrumentation and the British Society of Hypertension.

OBJECTIVE: To determine the accuracy of a new oscillometric home blood pressure (BP) monitor for arm BP measurement, the SAA-102, developed by the Sensacare Company. DESIGN: Evaluation of the SAA-102 was performed using validation protocols of the European Society of Hypertension (ESH), the Association for the Advancement of Medical Instrumentation (AAMI), and the British Hypertension Society (BHS). METHODS: The SAA-102 monitor was assessed on 33 participants according to ESH requirements, which are based on four zones of accuracy differing from the mercury standard by 5, 10, 15 mmHg or more. Then the oscillometric monitor was tested on 85 participants according to AAMI criteria which require a mean device-observers discrepancy within 5+/-8 mmHg. Finally, the electronic device was evaluated on 93 participants according to BHS requirements, which are based on five phases: before-use calibration, in-use assessment, after-use calibration, static device validation and report of the results. RESULTS: The SAA-102 passed all phases of the ESH international protocol for both systolic and diastolic blood pressure (SBP and DBP). The SAA-102 passed also AAMI criteria for SBP and DBP. The mean discrepancy between the SAA-102 and observers was 0.1+/-4.6 and -2.7+/-5.2 mmHg, for SBP and DBP, respectively. According to BHS protocol, the oscillometric monitor achieved final grading of A/A for SBP and DBP, respectively. CONCLUSION: These data show that the SAA-102 device satisfies ESH, AAMI, and BHS protocols for both SBP and DBP and may be recommended for everyday use for BP monitoring at home and in clinical practice.

Lifestyle, family history and progression of hypertension.

BACKGROUND: Unhealthy lifestyle practices are risk factors for future hypertension. OBJECTIVES: The aim of this study was to investigate the association between lifestyle changes over a 6-year period and the risk of developing sustained hypertension in a cohort of young hypertensive individuals, and to identify the predictors of lifestyle impairment over time. METHODS: Seven-hundred and eighty never-treated hypertensive HARVEST participants, 18-45 years old, were studied. RESULTS: Only modest mean behavioral changes were observed during follow-up. This, however, was the net result of many participants improving and others worsening their lifestyle. Participants with a family history of hypertension (FH+, n = 459) had more undesirable lifestyles (P = 0.004) and higher clinic and ambulatory blood pressures (P = 0.03) at baseline than participants without a family history of hypertension (FH-). During the 6-year follow-up, FH- individuals strikingly worsened their lifestyle while FH+ participants exhibited impressive improvements (P < 0.00001). Other predictors of lifestyle impairment were male gender (P = 0.003) and age (P = 0.02). Adoption of an unfavorable lifestyle was accompanied by an increased risk of developing sustained hypertension (P = 0.04). Initiation of drug therapy for hypertension was significantly higher among FH- than FH+ individuals (53 versus 45%, respectively; P = 0.045). CONCLUSIONS: 'Lower risk' FH- stage 1 hypertensive individuals may initially be at higher risk of developing more severe hypertension in comparison with their FH+ counterparts. This increased risk may be attributed to worsening of their lifestyle profiles over time. Healthy lifestyles should be emphasized to all hypertensive individuals including patients with favorable lifestyle profiles.

Effect of body weight loss on blood pressure after 6 years of follow-up in stage 1 hypertension.

BACKGROUND: Although it is known that weight reduction reduces blood pressure (BP) in overweight patients, the optimal body weight (BW) loss in terms of BP response is not yet established. We evaluated the relationship between decrease in BW and BP over time in 796 stage 1 hypertensives. METHODS: The 166 subjects who lost BW were divided into four groups according to percent of BW loss at the end of a 74-month follow-up (G1, >2% to 5%, G2, >5% to 9%, G3, >9% to 13%, and G4, >13%) and were compared to the 219 subjects without changes in BW (G0, -2% to +2%). The BW increased (>2%) in the remaining 411 subjects. RESULTS: Among subjects with BW loss there was a progressive decrease in final systolic BP associated with BW loss category up to G3 (P = .007), therefore at the end of follow-up G3 had systolic BP 6.2 mm Hg lower than G0 (P = .06). However, among G3 and G4 subjects systolic BP decrease was almost identical (-6.2 nu -5.7 mm Hg, respectively, P = not significant). Similar results were obtained for diastolic BP, which declined up to G3 (P = .013). G3 had final diastolic BP 3.6 mm Hg lower than G0 (P = .037), whereas change in diastolic BP in G4 subjects was similar to that in G0 (-0.9 nu +0.1 mm Hg, respectively, P = not significant). Similar results were obtained in the group with body mass index (BMI) >27 kg/m(2). CONCLUSIONS: Our results indicate that in stage 1 hypertensives followed for more than 6 years the dose-response relationship between BW loss and decrease in BP is not linear irrespective of initial BW. The BW loss >13% of initial weight did not elicit additional BP decrease.

Elevated C-reactive protein in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular and cerebrovascular disease. Inflammatory processes associated with OSA may contribute to cardiovascular morbidity in these patients. We tested the hypothesis that OSA patients have increased plasma C-reactive protein (CRP). METHODS AND RESULTS: We studied 22 patients (18 males and 4 females) with newly diagnosed OSA, who were free of other diseases, had never been treated for OSA, and were taking no medications. We compared CRP measurements in these patients to measurements obtained in 20 control subjects (15 males and 5 females) who were matched for age and body mass index, and in whom occult OSA was excluded. Plasma CRP levels were significantly higher in patients with OSA than in controls (median [range] 0.33 [0.09 to 2.73] versus 0.09 [0.02 to 0.9] mg/dL, P<0.0003). In multivariate analysis, CRP levels were independently associated with OSA severity (F=6.8, P=0.032). CONCLUSIONS: OSA is associated with elevated levels of CRP, a marker of inflammation and of cardiovascular risk. The severity of OSA is proportional to the CRP level.

Fish-rich diet, leptin, and body mass.

BACKGROUND: Leptin has been implicated in cardiovascular disease. A diet rich in fish has been associated with decreased cardiac and vascular risk. METHODS AND RESULTS: We examined the relationship between diet and leptin in 2 related homogeneous African tribal populations of Tanzania. One tribe consumes freshwater fish as their main diet component (n=279), and the other tribe consumes a primarily vegetarian diet (n=329). In multivariate analysis, plasma leptin levels were associated with type of diet (F=14.3, P<0.001), independent of age, body mass index, body fat, alcohol consumption, or insulin. Both male (2.5+/-2 [fish diet] versus 11.2+/-2.4 [vegetarian diet] ng/mL, P=0.017) and female (5.0+/-1.9 [fish diet] versus 11.8+/-1.4 [vegetarian diet] ng/mL, P=0.007) fish eaters had lower plasma leptin levels than did their vegetable diet counterparts, even though body mass index values were virtually identical. CONCLUSIONS: A diet rich in fish is associated with lower plasma leptin, independent of body fat. These findings may have implications for understanding the reduced cardiovascular risk in subjects on a high-fish diet.

Independent association between plasma leptin and C-reactive protein in healthy humans.

BACKGROUND: C-reactive protein (CRP) is synthesized from the liver and is regulated by cytokines, especially interleukin-6. Leptin, the adipocyte-derived protein product of the ob gene, is related to amount of body fat. The long form of the leptin receptor resembles cytokine receptors, which include the interleukin-6 receptor. Both leptin and CRP may be increased in women, in obesity, and in inflammation, and both have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk. We tested the hypothesis that leptin is associated with CRP levels independently of the influences of gender, body mass index (BMI), waist-to-hip ratio, and other variables. METHODS AND RESULTS: We studied 100 healthy volunteers (48 men, and 52 women). For all subjects, leptin was independently associated with CRP after adjustment for age, gender, BMI, waist-to-hip ratio, smoking, and alcohol consumption (F=12.39, P=0.0007). There was a strong and significant positive relationship between leptin and CRP in both women (R=0.61, P<0.0001) and men (R=0.55, P<0.0001) considered separately. The association between leptin and CRP was significant even after adjustment for age, BMI, waist-to-hip ratio, smoking, and alcohol consumption in women (F=7.13, P=0.01) and men (F=5.69, P=0.02). When only subjects with BMI <25 kg/m2 were considered (n=47), CRP was not linked to BMI (R=0.02, P=0.96), but a significant association between leptin and CRP was still evident (R=0.55, P<0.0001). CONCLUSIONS: Leptin and CRP levels are independently associated in normal humans, providing further evidence linking metabolic and inflammatory cardiovascular disease mechanisms.

C-344T polymorphism of the aldosterone synthase gene and blood pressure in the elderly: a population-based study.

OBJECTIVES: Whether the C-344T polymorphism of the aldosterone synthase gene is important for blood pressure control remains controversial. It has been proposed that an association between this polymorphism and blood pressure might be evident in elderly subjects. The aim of the present study was to test this hypothesis in an epidemiological context. DESIGN: A cross-sectional epidemiological evaluation of a highly homogeneous unselected general population of elderly Caucasians. METHODS: Lifestyle, medical history, anthropometrics, skinfold thickness, supine blood pressure, heart rate and biochemical measures were recorded in 437 subjects aged > or = 65 years living in a secluded valley. All were genotyped for C-344T allele status and underwent measurements of plasma aldosterone and renin. RESULTS: The C-344T genotypic frequency did not deviate from Hardy-Weinberg equilibrium. The aldosterone to renin ratio was 19% lower in the CC than in the TT genotype. Systolic blood pressure was significantly lower in subjects with the CC genotype, higher in the TT (+9.6 mmHg versus CC) and intermediate in the CT (+7.9 mmHg versus CC). Adjustment for age, gender, smoking and antihypertensive treatment did not affect this association. Diastolic blood pressure did not differ across genotypes. A significant increase of systolic blood pressure with increasing age and with increasing skinfold thickness was observed in the TT homozygotes but not in the C-carriers. CONCLUSIONS: These data support the concept that the C-344T polymorphism plays a role in controlling systolic blood pressure and the age-related increase in systolic blood pressure in response to age and to body fat, possibly through differences in modulation of aldosterone synthesis.

alpha-Adducin Gly460Trp polymorphism, left ventricular mass and plasma renin activity.

OBJECTIVE: Left ventricular hypertrophy (LVH) is associated with an increased risk for cardiovascular morbidity and mortality. Epidemiological studies suggest that LVH may be influenced by genetic factors. However, the evidence associating individual genes with left ventricular (LV) mass is inconsistent and contradictory. METHODS: We investigated the association between angiotensin-converting enzyme insertion/deletion, angiotensinogen and alpha-adducin polymorphisms with LV mass and plasma renin activity (PRA) in 162 men with mild, never-treated hypertension who were recruited for the Hypertension and Ambulatory Recording Venetia Study. The effect of each polymorphism on LV mass and PRA was tested in one-way analysis of covariance using LV mass index or PRA as the dependent variable after adjusting for covariates. RESULTS: The alpha-adducin polymorphism was the only individual polymorphism independently associated with LV mass index (F = 7.78, P= 0.006). Patients homozygous for the allele of that polymorphism had a LV mass index (123.4 +/- 10.5 g/m(2) ) significantly higher compared with heterozygotes (90.8 +/- 2.5 g/m(2) , P<0.01) or homozygotes (94.7 +/- 1.7 g/m(2) , P<0.05). These subjects also have significantly lower PRA (F = 4.2, P= 0.017). Albeit uncommon, 40% of homozygotes of the alpha-adducin polymorphism had LVH (odds ratio, 15.1; 95% confidence interval, 3.0-82.1). CONCLUSIONS: The homozygotic state of the allele of alpha-adducin polymorphism is independently associated with increased LV mass and low PRA. These data suggest that genetic considerations may contribute importantly to risk stratification, and perhaps therapeutic interventions targeted at LVH and the renin-angiotensin system in hypertensive patients.

Erythropoietin and obstructive sleep apnea.

OBJECTIVE: We tested the hypothesis that repetitive severe hypoxemia resulting from obstructive sleep apnea would increase serum erythropoietin, and that this increase would be attenuated by effective treatment of obstructive sleep apnea. METHODS: We studied healthy untreated patients with obstructive sleep apnea (18 severe and 10 very mild) before and after acute treatment with continuous positive airway pressure, and 12 healthy control subjects free of obstructive sleep apnea. RESULTS: Baseline erythropoietin levels before sleep were similar in the obstructive sleep apnea and control groups. However, erythropoietin levels increased (by 20%, P =.037) in patients with severe obstructive sleep apnea after 3.5 hours untreated (lowest O2, 77% +/- 3%), and decreased after 4 hours of continuous positive airway pressure treatment (P =.001). Erythropoietin responses in patients with severe obstructive sleep apnea were different (F = 4.0, P =.03) from controls, in whom erythropoietin levels remained stable throughout the night (P =.94). Erythropoietin responses were similar in very mild obstructive sleep apnea and controls (P =.58). CONCLUSIONS: Our results indicate that untreated severe obstructive sleep apnea results in increased erythropoietin, which decreases after continuous positive airway pressure treatment. Increased erythropoietin may be a potential reversible mechanism to explain the association between obstructive sleep apnea and cardiovascular disease.

Leptin is associated with the size of the apolipoprotein(a) particle in African tribal populations living on fish or vegetarian diet.

OBJECTIVE: Apolipoprotein(a) [or apo(a)] isoform size, which is strongly genetically determined, showed significant association with the cardiovascular risk. Subjects on a fish diet have lower lipoprotein(a) levels, larger apo(a) isoform sizes and lower leptin levels than their vegetarian diet counterparts. We hypothesized that leptin may contribute to a potential association between the type of diet and the size of apo(a) isoforms. METHODS: Anthropometric data, dietary nutrients, lipoprotein profile, plasma leptin levels, and apo(a) isoforms were evaluated in two related homogenous African tribal populations of Tanzania, one on a primarily freshwater fish diet (n=278), and the other on a vegetarian diet (n=326). RESULTS: We observed a strong negative association between leptin levels and size of each of the apo(a) isoforms in both fish and vegetable diet groups, and in both genders. However, leptin was not associated with levels of lipoprotein(a). In multivariate analysis, a strong and independent association between leptin and size of apo(a) isoforms was observed. The size of apo(a) isoforms was strongly associated with high and low leptin states. Subjects with low leptins had 30% larger sizes of apo(a) isoforms than their high leptin counterparts. CONCLUSIONS: High leptin subjects have smaller, potentially more atherogenic, apo(a) isoform sizes than low leptin ones. We suggest that omega-3 rich diet can influence the levels of apo(a) and/or Lp(a) even though they are mainly genetically determined. These findings may have implications for understanding the interaction between leptin and cardiovascular risk.

Validation of the SAW-102 wrist home blood pressure monitor according to the protocols of the British Hypertension Society, the Association for the Advancement of Medical Instrumentation, and the European Society of Hypertension.

OBJECTIVE: To determine the accuracy of the SAW-102 wrist oscillometric blood pressure monitor developed by the Sensacare Company according to the protocols of the European Society of Hypertension (ESH), the Association for the Advancement of Medical Instrumentation (AAMI), and the British Hypertension Society (BHS). METHODS: SAW-102 was assessed on 33 participants according to ESH requirements, based on four zones of accuracy differing from the mercury standard by 5, 10, 15 mmHg or more. Then SAW-102 was tested on 85 participants according to AAMI criteria requiring mean device-observers discrepancy within 5+/-8 mmHg. Subsequently, SAW-102 was evaluated on 88 participants according to BHS requirements. Finally, 15 participants with wrist circumference greater than the manufacturer's recommendation (19.5 cm) were studied (large wrist group). Efforts were made to secure a stable position of wrist and arm at the heart level. RESULTS: SAW-102 passed all phases of ESH international protocol for both systolic blood pressure (SBP) and diastolic blood pressure (DBP). SAW-102 passed AAMI criteria with mean differences between SAW-102 and observers of 3.8+/-7.5 and 1.5+/-6.0 mmHg, SBP and DPB, respectively. According to BHS protocol, the device achieved final grading of B/B for SBP and DBP, respectively. Large wrist group did not pass the first phase of ESH protocol. CONCLUSION: This study demonstrated that SAW-102 meets the BHS, ESH, and AAMI standards when measurements are done at the heart level and when the manufacturer's specifications, regarding wrist circumference, are respected. Our data also indicate that exceeding 19.5 cm wrist circumference is accompanied by dramatic decrease of the accuracy of the device.

Comparison of clinical features of arrhythmogenic right ventricular cardiomyopathy in men versus women.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease characterized by myocardial necrosis followed by fibrous-fatty replacement. The pathologic process constitutes the basis for ventricular arrhythmias due to re-entrant circuits. Even if this genetic disease is transmitted in the majority of cases with autosomal dominant trait, in all reported series ARVC is prevalent in men. In this study we investigate the impact that gender may have on clinical presentation in a large series of patients with ARVC. A total of 171 consecutive patients (mean 29 +/- 12 years, range 13 to 65) affected by ARVC were examined with family and personal history, 12-lead electrocardiogram (ECG), 24-hour ECG, signal-averaged ECG, and echocardiogram. Moreover, electrophysiological study and ventricular angiography were performed in selected cases. In the 171 subjects, 71% were men and 29% women (p = 0.02). No gender differences were found considering the age at the time of diagnosis and of study enrolment and the prevalence of index cases and family members. The genders differed in prevalence of abnormal ECG (69% vs 52%, p = 0.036) and presence of late potentials (60% vs 40%, p = 0.01). Moreover, men had larger right ventricular dimensions and practiced competitive sports more frequently (26% vs 14%, p <0.001). Nonetheless, gender was not associated with a high incidence of life-threatening ventricular arrhythmias or with a poor outcome. In conclusion, our data show that diagnosis of ARVC is less common in female patients, who present a higher prevalence of mild forms. Nonetheless, the degree of electrical instability does not differ significantly between genders in affected subjects. Even if ARVC remains mainly a male disease, gender does not have a role in patients' outcome. The cause of the under-representation of women is not clear, even if potentially important factors such as sexual hormones and physical activity could play a role.

Plasma levels of adiponectin, a novel adipocyte-derived hormone, in sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with obesity, sympathetic activation, systemic inflammation, and cardiovascular morbidity. Obesity, beta-adrenergic agonists, and inflammation are linked to decreased expression and/or secretion of an adipose tissue-derived antiatherogenic hormone, adiponectin. The purpose of the study was to investigate whether OSA affected plasma levels of adiponectin, which might help explain OSA-associated cardiovascular morbidity. RESEARCH METHODS AND PROCEDURES: We randomly selected 68 otherwise healthy male subjects, either with moderate/severe OSA [apnea-hypopnea index (AHI)>or=20; n=35] or without OSA (AHI

G-protein beta3-subunit gene 825T allele and hypertension: a longitudinal study in young grade I hypertensives.

The 825T allele of the GNB3 gene has been associated with essential hypertension and obesity in cross-sectional studies. We have therefore planned a longitudinal cohort study to assess whether the GNB3 825T allele is predictive of blood pressure increase in young subjects with grade I hypertension. We genotyped at the GNB3 825 locus 461 participants of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) study (age, 18 to 45 years) at low cardiovascular risk, according to 1999 ISH/WHO criteria. The study end point was eligibility for antihypertensive medication, that is, progression to grade II hypertension during the first year of observation or office systolic blood pressure > or =150 mm Hg and/or office diastolic blood pressure > or =95 mm Hg in two later consecutive visits during follow-up. At baseline, there was no statistically significant difference among genotypes with respect to body mass index, blood pressure, and heart rate. During follow-up (mean, 4.7 years), 113 (51.1%) patients with CC genotype and 145 (60.4%) patients with TT/TC genotype reached the end point. According to survival analysis, the patients carrying the 825T allele had an increased risk of reaching the blood pressure end point (CI, 1.108 to 1.843; P=0.006). In young patients with grade I hypertension, the 825T allele is associated with increased risk of progression to more severe hypertension requiring antihypertensive therapy. The GNB3 825T allele may be considered a genetic marker of predisposition for hypertension.

Relationship between muscle sympathetic nerve activity and diurnal blood pressure profile.

The physiological mechanisms mediating the variability and diurnal rhythm of blood pressure are unclear. We tested the hypothesis that resting sympathetic activity is linked to the variability characteristics and 24-hour profile of ambulatory blood pressure measurements. We evaluated the relationship between muscle sympathetic nerve activity (MSNA) and the level, variability, and nocturnal fall of ambulatory blood pressure in 69 normal men. Subjects were subdivided according to the tertiles of MSNA distributions. Mean 24-hour blood pressure was not significantly different across the 3 groups. Compared with subjects in the first tertile (lowest MSNA, <18 bursts/min), subjects in the third tertile (highest MSNA, >25 bursts/min) had significantly greater daytime blood pressure variability, whether expressed as absolute values (10.2+/-0.5 versus 8.1+/-0.4 mm Hg for systolic blood pressure and 9.4+/-0.4 versus 7.2+/-0.4 mm Hg for diastolic blood pressure; P<0.01 for both comparisons) or as variation coefficients (8.1+/-0.4% versus 6.6+/-0.3% for systolic blood pressure and 12.7+/-0.7% versus 10.1+/-0.6% for diastolic blood pressure; P<0.01 for both comparisons). Subjects in the third tertile also had a more striking absolute and percentage fall in systolic blood pressure from daytime to nighttime than subjects in the first tertile (17+/-2 versus 10+/-2 mm Hg, P=0.02, or 13+/-1% versus 8.2+/-1.4%, P=0.02). In conclusion, higher resting measurements of sympathetic traffic are associated with greater daytime blood pressure variability and a more marked nocturnal decline in blood pressure in normal subjects. These findings suggest that sympathetic neural mechanisms may contribute importantly to the regulation of blood pressure over the 24-hour period.

Prevalence and clinical significance of isolated ambulatory hypertension in young subjects screened for stage 1 hypertension.

Little is known about the clinical significance of isolated ambulatory hypertension, a condition characterized by low office but elevated ambulatory blood pressure. This study aimed to investigate the prevalence and the predictive value of isolated ambulatory hypertension diagnosed after 3 months of observation for the development of sustained hypertension within a cohort of 871 never-treated stage-1 hypertensive subjects. The study end point was progression to more severe hypertension and need of antihypertensive medication. In 244 subjects (28%), clinic blood pressure declined to <140/90 mm Hg after 3 months. Of these, 124 (14.2% of total) had low clinic and ambulatory blood pressures after 3 months (nonhypertensive subjects), whereas 120 subjects (13.8% of total) showed low clinic but elevated ambulatory blood pressure (isolated ambulatory hypertension). During the 6 years of observation, the number of end points based on multiple clinic blood pressure readings progressively increased from the nonhypertensive subjects (19%) to the subjects with isolated ambulatory hypertension (35%) and to the subjects with high clinic and high ambulatory blood pressures (65%, P<0.0001). In an adjusted proportional hazard model, isolated ambulatory hypertension status was associated with a 2.2 (P=0.02) increase in the risk of reaching the end point in comparison with the nonhypertensive subjects. Final ambulatory systolic blood pressure was also higher in the former than the latter (P=0.03). Our results indicate that among subjects screened for stage 1 hypertension, individuals with isolated ambulatory hypertension after 3 months of observation have increased risk of developing sustained hypertension in later life compared with subjects in whom both clinic and ambulatory blood pressures are normal.

Physical activity and angiotensin-converting enzyme gene polymorphism in mild hypertensives.

It has been suggested that the insertion(I) allele of the I/deletion(D) polymorphism of the angiotensin converting enzyme (ACE) gene is associated with endurance exercise and increased physical conditioning in response to this type of exercise. To investigate the association between the ACE I/D polymorphism and physical activity status in 355 never treated, stage I hypertensives (265 men, 90 women, mean age: 33 +/- 9 years), in whom power exercise is contraindicated, participants of the HARVEST study. Physical activity was assessed using a standardized questionnaire. BMI and age did not vary among genotypes. None of active subjects performed power oriented exercises. ACE I/D frequencies (II-18%, ID-55%, DD-27%) were in Hardy-Weinberg equilibrium. Sedentary lifestyle was more common among DD than II hypertensives (76% in DD, and 48% in II, Chi(2) = 13.9, P = 0.001). In stepwise MANOVA using age, marital status, profession, sex, and ACE genotype as predictors of physical activity, marital status (F = 24.4, P < 0.0001) and ACE genotype (F = 16.03, P < 0.0001) contributed to more than 50% of the variance in physical activity status of the population. Our results suggest that the ACE I/D polymorphism may be a specific genetic factor associated with physical activity levels in free-living borderline and mild hypertensive subjects.