Short-term external counterpulsation augments cerebral blood flow and tissue oxygenation in chronic cerebrovascular occlusive disease.

BACKGROUND AND PURPOSE: External counterpulsation improves cerebral perfusion velocity in acute stroke and may stimulate collateral artery growth. However, whether (non-acute) at-risk patients with high-grade carotid artery disease may benefit from counterpulsation needs to be validated. METHODS: Twenty-eight patients (71 ± 6.5 years, five women) with asymptomatic unilateral chronic severe internal carotid artery stenosis (>70%) or occlusion were randomized to receive 20 min active counterpulsation followed by sham treatment or vice versa. Cerebral blood flow velocity (CBFV) (measured bilaterally by transcranial middle cerebral artery Doppler), tissue oxygenation index (TOI) (measured over the bilateral prefrontal cortex by near-infrared spectroscopy) and cerebral hemodynamic parameters, such as relative pulse slope index (RPSI), were monitored. RESULTS: Ipsilateral mean CBFV (ΔVmean +3.5 ± 1.2 cm/s) and tissue oxygenation (ΔTOI +2.86 ± 0.8) increased significantly during active counterpulsation compared to baseline, whilst the sham had little effect (ΔVmean +1.13 ± 1.1 cm/s; ΔTOI +1.25 ± 0.65). On contralateral sides, neither counterpulsation nor sham control had any effect on either parameter. During counterpulsation, early dynamic changes in ΔRPSI of the ipsilateral CBFV signal predicted improved tissue oxygenation during counterpulsation (odds ratio 1.179, 95% confidence interval 1.01-1.51), whilst baseline cerebrovascular reactivity to hypercapnia failed to show an association. CONCLUSIONS: In patients with high-grade carotid disease, ipsilateral cerebral oxygenation and blood flow velocity are increased by counterpulsation. This is a necessary condition for the stimulation of regenerative collateral artery growth and thus a therapeutic concept for the prevention of cerebral ischaemia. This study provides a rationale for further clinical investigations on the long-term effects of counterpulsation on cerebral hemodynamics and collateral growth.

[Assessment of subjective physical well-being in heart failure : Validation of the FEW16 questionnaire]. / Erfassung des subjektiven körperlichen Wohlbefindens bei Herzinsuffizienz : Validierung des FEW16-Fragebogens.

INTRODUCTION: Improvement in the quality of life (QoL) is a major goal of therapy for heart failure (HF) patients. Physical well-being as an important component of QoL has not yet been sufficiently covered by disease-specific assessment instruments. The aim of the study was to validate the questionnaire for assessing subjective physical well-being (FEW16) in HF patients with preserved ejection fraction (HFpEF) from the exercise training in diastolic heart failure (Ex-DHF­P) trial. METHOD: A total of 64 HFpEF patients (65 years, 56 % female) were randomized to usual routine treatment with (n = 44) or without training (n = 20). At baseline and 3 months, patients were clinically evaluated and assessed using appropriate questionnaires on the QoL (SF36), physical well-being (FEW16) and depression (PHQ-D). RESULTS: The FEW16 showed good values for Cronbachs' alpha coefficients (0.85-0.93). The cross-validity with SF36 and PHQ-D was highly significant but more so for psychological aspects. At baseline, the FEW16 score correlated with age, the subscale resilience with age and the 6 min walking distance test. At follow-up, the total and resilience scores had improved in the training group. In contrast to the SF36, the FEW16 did not detect differences between the groups in Ex-DHF­P. DISCUSSION: The FEW16 questionnaire showed good internal consistency and correlation with SF36, its total score and resilience had improved after training; however, it did not reflect different changes between the study groups. The FEW16 is therefore more suited to assess general/mental well-being than the subjective physical well-being.

Validation of the FEW16 questionnaire for the assessment of physical well-being in patients with heart failure with reduced ejection fraction: results from the CIBIS-ELD study.

AIMS: Patients with heart failure (HF) commonly suffer from severe impairment of quality of life (QoL). One main goal of HF treatment is improvement of QoL. Physical well-being is an essential component of QoL. To enable assessment of physical well-being in HF patients, we validated the FEW16 questionnaire in a prospective study with patients from the Cardiac Insufficiency Bisoprolol Study in ELDerly. METHODS AND RESULTS: In 127 HF patients (age 73 ± 5.5 years, 72% male, 60% New York Heart Association class II, left ventricular ejection fraction 37 ± 8.5%), we measured physical well-being (FEW16), QoL [36-Item Short-Form Health Survey (SF36)], and depressive symptoms [PRIME MD Patient Health Questionnaire German short version for depression (PHQ-D)] at baseline and two follow-up visits, and correlated FEW16 scores with QoL data and clinical parameters. FEW16 mean scores are 3.04 ± 1.04 at baseline, 3.19 ± 0.94 after 3 months, and 2.77 ± 0.94 after 2-4 years. We assessed data quality, scale assumptions, and construct validity and reliability. Cronbach's alpha for subscales resilience: 0.84; ability to enjoy: 0.80; vitality: 0.88; inner peace: 0.87; total score: 0.95. Intraclass correlation coefficient (ICC) is 0.87 (95% CI 0.84-0.89, ICC (1.4). Pearson's correlations of FEW16 with SF36 and PHQ-D were significant. Six minutes walking distance and heart rate correlated significantly with the FEW16 total score. CONCLUSIONS: The FEW16 showed good reliability, internal consistency, and intraclass correlation. FEW16 scores correlated well with psychological and physical well-being (SF36) and clinical markers of exercise tolerance (6 min walk test and heart rate). Our results indicate a strong correlation of self-reported physical well-being with psychological factors. FEW16 values at baseline predicted the development of several aspects of QoL during beta-blocker up-titration.

Genetic influences on the pharmacokinetics of orally and intravenously administered digoxin as exhibited by monozygotic twins.

The expression and function of the drug transporter P-glycoprotein are highly variable. Environmental and genetic factors contribute to this variation. We studied the disposition of digoxin, a frequently used probe drug for P-glycoprotein function in humans, in monozygotic (MZ) twins and found that digoxin pharmacokinetics after oral and intravenous administration are highly correlated within MZ twins, supporting the hypothesis of a robust contribution from genetic variance. Our study suggests that studies involving twins could be more widely applied to elucidate pharmacogenetics.

Improvement of fractional flow reserve and collateral flow by treatment with external counterpulsation (Art.Net.-2 Trial).

BACKGROUND: Arteriogenesis (collateral artery growth) is nature's most efficient rescue mechanism to overcome the fatal consequences of arterial occlusion or stenosis. The goal of this trial was to investigate the effect of external counterpulsation (ECP) on coronary collateral artery growth. MATERIALS AND METHODS: A total of 23 patients (age 61 +/- 2.5 years) with stable coronary artery disease and at least one haemodynamic significant stenosis eligible for percutaneous coronary intervention were prospectively recruited into the two study groups in a 2 : 1 manner (ECP : control). One group (ECP group, n = 16) underwent 35 1-h sessions of ECP in 7 weeks. In the control group (n = 7), the natural course of collateral circulation over 7 weeks was evaluated. All patients underwent a cardiac catheterization at baseline and after 7 weeks, with invasive measurements of the pressure-derived collateral flow index (CFIp, primary endpoint) and fractional flow reserve (FFR). RESULTS: In the ECP group, the CFIp (from 0.08 +/- 0.01 to 0.15 +/- 0.02; P < 0.001) and FFR (from 0.68 +/- 0.03 to 0.79 +/- 0.03; P = 0.001) improved significantly, while in the control group no change was observed. Only the ECP group showed a reduction of the Canadian Cardiovascular Society (CCS, P = 0.008) and New York Heart Association (NYHA, P < 0.001) classification. CONCLUSION: In this study, we provide direct functional evidence for the stimulation of coronary arteriogenesis via ECP in patients with stable coronary artery disease. These data might open a novel noninvasive and preventive treatment avenue for patients with non-acute vascular stenotic disease.

Genetic influence on blood pressure and lipid parameters in a sample of Polish twins.

We studied 76 healthy monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs (mean age 35 +/- 8 years, body mass index, BMI, 23.6 +/- 3.9 kg/m2) to determine genetic and environmental contributions to systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) and serum lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-chol), high-density lipoprotein cholesterol (HDL-chol) and triglycerides (TG)I. SBP, DBP and HR were measured clinically and by ambulatory blood pressure monitoring (ABPM). Parameters of the genetic models for age-, sex- and BMI-adjusted data were estimated by model fitting and path analysis technique using LISREL 8. We found significant genetic effect on SBP and DBP for both clinical and ABP measurements, ranging from 37% for night-time ambulatory DBP to 79% for daytime ambulatory SBP. Estimates of genetic effects were higher for daytime than night-time ABP values, and higher for ambulatory 24-h SBP than office SBP measurements, with the reverse true for DBP. Significant genetic effect on HR ranged from 59% for office measurements to 69% for 24-h mean values. In summary, we also found genetic effect on TC, LDL-chol and HDL-chol with estimates ranging from 36% to 64%, but not on TG. Furthermore, a shared environmental component for TG was found, estimated at 36%. We showed significant genetic effect on both office and ambulatory BP and HR, with stronger genetic effect on daytime than night-time BP. We also found genetic effect on TC and lipoprotein fractions, but no significant genetic effect on TG. Environmental factors influencing serum TG, such as alcohol consumption, may explain the apparent lack of genetic effect in this healthy, non-obese population.

Autonomic nervous system function in patients with monogenic hypertension and brachydactyly: a field study in north-eastern Turkey.

Laboratory studies in patients with autosomal-dominant hypertension and brachydactyly showed increased sensitivity to sympathetic stimuli and severe abnormalities in baroreflex buffering. To further elucidate the mechanisms by which impaired baroreflex sensitivity could influence blood pressure (BP), we conducted autonomic testing under field conditions. We studied 17 hypertensive affected (13 to 48 years, BMI 22.7 +/- 6.5 kg/m(2), 160 +/- 23/98 +/- 15 mm Hg) and 12 normotensive non-affected (9 to 60 years, BMI 24.0 +/- 4.7 kg/m(2), 120 +/- 16/70 +/- 10 mm Hg) family members. Pulse intervals and finger BP were measured using the Portapres device. Valsalva ratio, the blood pressure overshoot during phase IV of the Valsalva manoeuver, the Ewing coefficient (RR30/15 ratio), and heart rate and BP variability were similar in affected and non-affected family members. Overall, baroreflex sensitivity calculated using the cross-spectral (BRSLF, BRSHF) and sequence techniques (BRS+, BRS-) was not different between the groups. However, in younger family members, BRS+ was 12 +/- 3.7 and 22 +/- 13 msec/mm Hg in affected and in non-affected family members, respectively. The decline in BRS with age and with increasing blood pressure was absent in affected family members. We conclude that autonomic reflex testing conducted under field conditions is not impaired in patients with monogenic hypertension and brachydactyly. However, noninvasive testing showed impaired baroreflex control of heart rate at a young age. The reduced BRS in young family members with moderate arterial hypertension may suggest that the impaired baroreflex function is not secondary to the hypertension but rather a primary abnormality, which aggravates the progression of hypertension.

Beta-2 adrenergic receptor gene variations and blood pressure under stress in normal twins.

We tested the hypothesis that blood pressure (BP) responses to physical and mental stress are associated with polymorphisms in the beta-2 adrenergic receptor (AR) gene. We studied normotensive, young, monozygotic (MZ) and dizygotic (DZ) twins. The subjects underwent automated BP measurements at the brachial and digital arteries and were subjected to mental arithmetic and cold pressor stress. We used allele-specific PCR to genotype four single nucleotide polymorphisms in the beta-2 AR gene. The most functionally relevant polymorphism in the beta-2 AR gene, Arg16/Gly, was associated with systolic and diastolic BP under resting conditions, during mental arithmetic, and during the cold pressor test, as well as with the increase in diastolic BP during both forms of stress. These findings support a role for the beta-2 AR gene in BP regulation. They also indicate that the beta-2 AR gene influences the level of not only resting but also stress-related BP.

Genetic influences on baroreflex function in normal twins.

Blood pressure and heart rate are strongly influenced by genetic factors; however, despite the pivotal role of genetics in short-term cardiovascular regulation, little is known about the genetic contribution to baroreflex function. We assessed genetic influence on baroreflex sensitivity (BRS) in 149 twin pairs (88 monozygotic of age 33+/-13 years and BMI 23+/-4 kg/m(2) and 61 dizygotic of age 33+/-11 years and BMI 24+/-4 kg/m(2)). ECG and finger arterial blood pressures were measured continuously under resting conditions. BRS values were calculated by use of cross-spectral analysis (baroreflex slope calculated as mean value of transfer function between systolic blood pressure and the R-R interval in the low-frequency band [BRSLF] and baroreflex slope calculated as the mean value of transfer function between systolic blood pressure and R-R interval in the respiratory frequency band [BRSHF]) and the sequence technique (BRS+, BRS-). Heritability (h(2)) was estimated with a path-modeling approach. BRS values did not differ significantly between groups (monozygotic, BRSLF, 17+/-13; BRSHF, 21+/-18; BRS+, 19+/-16; and BRS-, 21+/-15, and dizygotic, BRSLF, 16+/-9; BRSHF, 20+/-14; BRS+, 18+/-10; and BRS-, 20+/-11 ms/mm Hg), and were significantly correlated (P:<0.001). When variances and covariances for monozygotic and dizygotic twins were compared, significant correlations were found for BRS in monozygotic (range, r=0.38 to 0.48) but not in dizygotic twin pairs (r=-0.03 to 0.09). Thus, BRS is heritable; the variability can be explained by genetic influences (P:<0.01; h(2) range, 0.36 to 0.44). The genetic influence on BRS remained strong after correction for BMI and blood pressure. Therefore, BRS is strongly genetically determined, probably by different genes than are resting blood pressure and BMI.

Association of a uteroglobin polymorphism with rate of progression in patients with IgA nephropathy.

Uteroglobin gene-disrupted mice develop a nephritis very similar to immunoglobulin A (IgA) nephropathy. Megsin codes for a protein overexpressed in mesangium in patients with IgA nephropathy. Both are candidate genes that might have variants associated with an accelerated progression in patients with IgA nephropathy. We performed an association study of patients with IgA nephropathy and matching control subjects to test whether the G38A polymorphism in the uteroglobin gene, the C2093T polymorphism in the megsin gene, or the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism is associated with IgA nephropathy or rate of disease progression in patients with IgA nephropathy. Of 110 patients with IgA nephropathy, 87 patients were followed up for at least 3 years for the progression study. We also studied 104 healthy volunteers. The uteroglobin, megsin, and ACE polymorphisms were not distributed differently in the 110 patients with IgA nephropathy compared with healthy controls; Hardy-Weinberg equilibrium criteria were fulfilled. The GG genotype of the G38A uteroglobin polymorphism was more common in patients with progression (odds ratio [OR], 3.5; P< 0.006) than the AG+AA genotypes. The G allele was also more common (OR, 2.6; P< 0.009) in patients with versus without progression. The 1/serum creatinine over time plot (in deciliters per milligram per day) was sevenfold steeper in GG patients than the other two genotypes (P = 0.08). No significant associations with disease progression were found for the other gene polymorphisms, and a multivariate analysis showed no interactions. We suggest the hypothesis that the uteroglobin gene contains variant(s) with a bearing on progression rate in patients with IgA nephropathy.

Chlamydia pneumoniae DNA in non-coronary atherosclerotic plaques and circulating leukocytes.

Earlier studies have associated atherosclerosis with Chlamydia pneumoniae infection. C. pneumoniae may circulate via monocytes and migrate into plaques by leukocyte infiltration; however, detection is difficult. We developed a novel polymerase chain reaction (PCR) method to test the hypothesis that C. pneumoniae DNA in circulating leukocytes is correlated with C. pneumoniae DNA in plaque material and that C. pneumoniae copy number is associated with disease severity. We obtained plaques from 130 patients who underwent surgery for carotid stenosis, aneurysm, or peripheral vascular disease. From 60 patients and 51 normal control subjects we also obtained circulating leukocytes. The C. pneumoniae 16 S rRNA gene was amplified with a highly specific quantitative PCR protocol relying on the TaqMan technology. Immunohistochemistry was performed with antibody against the C. pneumoniae outer membrane protein. C. pneumoniae DNA was present in 25% of atherosclerotic plaques and 20% of circulating leukocytes from patients. The copy number was not correlated with disease severity. C. pneumoniae DNA was more common in younger patients and smokers. C. pneumoniae antibody titers, C-reactive protein, fibrinogen, leukocyte count, cholesterol, and diabetes were not associated with C. pneumoniae DNA. Although immunostaining of plaque and PCR results were highly correlated, we found no relationship between C. pneumoniae DNA in plaques and that in circulating leukocytes. Finally, 13% of normal control subjects had positive leukocytes; however, their copy number was significantly lower than that of the patients. C. pneumoniae DNA is frequent in atherosclerotic plaques and is correlated with positive immunohistochemistry. C. pneumoniae DNA may also be found in circulating leukocytes; however, infected leukocytes and plaques do not coincide. Serology is unreliable in predicting C. pneumoniae DNA. Smoking increases the risk of harboring C. pneumoniae DNA. Our results do not suggest that either test for antibodies or C. pneumoniae DNA from leukocytes in blood is of value in predicting infected plaques.

TNF-alpha-mediated neutrophil apoptosis involves Ly-GDI, a Rho GTPase regulator.

We investigated intracellular signaling events involved in fibronectin-accelerated TNF-alpha-mediated PMN apoptosis by means of 2-D gel electrophoresis and western blotting. Proteins were sequenced with electrospray ionization mass spectrometry. Apoptosis was quantitated by flow cytometry. We detected a cluster of acidic, high molecular-weight proteins that were only tyrosine phosphorylated when TNF-alpha-treated PMN interacted with fibronectin. Sequence analysis revealed that one of these proteins was Ly-GDI, a regulator of Rho GTPases. Fibronectin increased the TNF-alpha-induced Ly-GDI cleavage, yielding a 23-kD fragment. At 8 h, intact Ly-GDI was decreased to 33% on fibronectin, compared with 69% on PolyHema (P<0.05). Inhibition of tyrosine phosphorylation prevented phosphorylation of Ly-GDI, fibronectin-accelerated Ly-GDI cleavage, and fibronectin-accelerated apoptosis in TNF-alpha-treated PMN. We found that Ly-GDI cleavage was dependent on caspase-3 activation and that caspase-3 inhibition decreased apoptosis. We conclude that tyrosine phosphorylation of Ly-GDI, followed by increased caspase-3-mediated Ly-GDI cleavage, is a signaling event associated with accelerated TNF-alpha-mediated apoptosis on fibronectin.

Support for linkage of familial combined hyperlipidemia to chromosome 1q21-q23 in Chinese and German families.

We examined familial combined hyperlipidemia (FCHL) families from nonisolated regions in Germany and China to see if we could corroborate support for a chromosome 1q FCHL locus in more general populations. We recruited 24 German families with 137 members, 92 of whom met the criteria of affected in terms of the low density lipoprotein (LDL) and triglyceride levels in excess of the 90th percentile for age and gender. In China, we recruited 12 families with a total of 81 members. All affected persons had total cholesterol concentrations >240 mg/dl and triglyceride concentrations >250 mg/dl. We examined the markers APOA2, D1S1677, D1S104, D1S194, D1S426, and D1S196. Two-point linkage analysis allowing for heterogeneity gave a maximum linkage of disorder score (HLOD) of 2.60 right over D1S194, estimating the proportion of linked families at 36%. This marker is adjacent to D1S104. The evidence for linkage was roughly the same both in the German (HLOD 1.40) and Chinese families (HLOD 1.52). Marker D1S194 is close to the retinoid X receptor (RXR) gene locus, which was found to be linked to triglyceride levels in an earlier twin study from our laboratory. We interpret our observations as encouraging support for the recent findings indicating the presence of a gene for FCHL on chromosome 1q. Furthermore, since DIS194 is adjacent to the gene for the RXR, we suggest that RXR is an attractive candidate for involvement in FCHL.

beta-2 adrenergic receptor gene variations, blood pressure, and heart size in normal twins.

Genetic variability, which influences cardiovascular phenotypes in normal persons, is likely to be relevant to cardiovascular disease. We studied normal monozygotic and dizygotic twins and found strong genetic influences on blood pressure and heart size. We then relied on the dizygotic twins and their parents to apply molecular genetic techniques. We performed a linkage analysis with markers close to the beta-2 adrenergic receptor (AR) gene locus in the dizygotic twins and their parents and found strong evidence for linkage to the quantitative traits of blood pressure and heart size. We then used allele-specific polymerase chain reaction to genotype the subjects further. We performed an association analysis and found that 4 functionally relevant polymorphisms in the beta-2 AR gene, namely Arg16/Gly, Gln27/Glu, Thr164/Ile, and a variant in the promoter region (-47C/T), were variably associated with blood pressure and heart size differences but were in linkage dysequilibrium with each other. A subsequent conditional analysis suggested that the Arg16/Gly polymorphism exerted the predominant effect. These findings underscore the importance of the beta-2 AR gene to blood pressure regulation, heart size, and probably to the development of hypertension. We suggest that a combined linkage and association approach will elucidate the genetic variability influencing blood pressure and other cardiovascular phenotypes.

A cholesterol-lowering gene maps to chromosome 13q.

A cholesterol-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to those in persons with heterozygous FH. We studied such a family with FH that also had members without FH and with lower-than-normal LDL levels. We performed linkage analyses and identified a locus at 13q, defined by markers D13S156 and D13S158. FASTLINK and GENEHUNTER yielded LOD scores >5 and >4, respectively, whereas an affected-sib-pair analysis gave a peak multipoint LOD score of 4.8, corresponding to a P value of 1.26x10-6. A multipoint quantitative-trait-locus (QTL) linkage analysis with maximum-likelihood binomial QTL verified this locus as a QTL for LDL levels. To test the relevance of this QTL in an independent normal population, we studied MZ and DZ twin subjects. An MZ-DZ comparison confirmed genetic variance with regard to lipid concentrations. We then performed an identity-by-descent linkage analysis on the DZ twins, with markers at the 13q locus. We found strong evidence for linkage at this locus with LDL (P<.0002), HDL (P<.004), total cholesterol (P<.0002), and body-mass index (P<.0001). These data provide support for the existence of a new gene influencing lipid concentrations in humans.

Peroxisome proliferator-activated receptor gamma gene locus is related to body mass index and lipid values in healthy nonobese subjects.

The peroxisome proliferator-activated receptor gamma (PPARgamma) gene has been implicated in morbid obesity and is important to lipid and carbohydrate metabolism. However, the relevance of gene variations in healthy nonobese subjects has not been defined. We recruited monozygotic and dizygotic healthy nonobese twin subjects to test the hypothesis that the PPARgamma gene is important to body mass index and lipid concentrations in healthy nonobese subjects. Both linkage and association strategies were used in the same dizygotic twins. The PPARgamma gene locus was linked (P<0.01) to high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body mass index as quantitative traits. A biallelic variant in the PPARgamma gene was associated with high-density lipoprotein cholesterol and body mass index (P<0.05). We also looked for linkage between the same variables and the retinoic X receptor gene locus. This locus was linked to total and low-density lipoprotein cholesterol as well as triglycerides. We conclude that the PPARgamma gene is highly relevant to lipid metabolism and body mass index, not only in the morbidly obese but also in healthy nonobese subjects. The same appears to be true for its binding partner. Sequencing these genes in twins would serve to identify gene variations contributing to body mass index and lipid concentrations in healthy nonobese subjects.

Linkage but lack of association for blood pressure and the alpha-adducin locus in normotensive twins.

BACKGROUND: alpha-adducin is a cytoskeletal protein involved with sodium-pump activity in the renal tubule. The alpha-adducin gene locus has been linked to hypertension and a polymorphism identified which is associated with hypertension; however, the role of the alpha-adducin gene locus in normal blood pressure regulation is not defined. We performed a combined linkage and association study in normotensive monozygotic (MZ) and dizygotic (DZ) twins and their parents to address this issue. METHODS: We studied 126 MZ and 70 DZ twin pairs and parents of DZ twins. Blood pressure values and responses to a cold pressor test were obtained. Cardiac dimensions were measured echocardiographically. Three microsatellites adjacent to the alpha-adducin gene were studied as well as the 460 Trp mutation in the alpha-adducin gene. RESULTS: We obtained strong evidence for linkage (P< 0.001) between the alpha-adducin gene locus and systolic blood pressure. However, we were not able to associate the 460 Trp mutation with higher blood pressures, cold pressor responses or cardiac dimensions. CONCLUSIONS: The alpha-adducin gene locus is relevant to blood pressure regulation in normal subjects. Failure to find an association between higher blood pressures and the 460 Trp mutation suggests that this mutation may become important only when hypertension is triggered, or that other variations in alpha-adducin are present which have not yet been discovered.

Genetic and environmental influences on coping styles: a twin study.

OBJECTIVE: Coping styles are generally considered to be environmentally driven, primarily by family influences. However, because personality traits are commonly influenced by genetic effects, we hypothesized that heredity is also important for coping. METHODS: We tested this hypothesis by assessing 19 coping styles, as well as four secondary coping factors, by questionnaire in 212 pairs of monozygotic and dizygotic twins. We then examined heredity by structural equation modeling. RESULTS: All coping styles showed evidence of genetic influences. The coping styles shared one common genetic factor. In addition, each coping style was also influenced by other separate genetic factors. Shared environment had no significant influence on coping styles. Three of 19 more specific coping styles showed shared environmental effects as well as genetic influences, 14 were solely under genetic influences, and two showed only shared environment effects. CONCLUSIONS: We suggest that hereditary effects on certain coping style preferences cannot be explained solely by genetic influences on major personality traits and temperament. An analysis of the relationships between coping and personality in twin subjects may elucidate the distinction between genetic and environmental effects.