[Laboratory input. General practitioners positive about reflective testing]. / Eigen inbreng van het laboratorium. Huisartsen positief over 'reflecterend testen'.

OBJECTIVE: To investigate the opinion of general practitioners on reflective testing, i.e. the practice of additional tests being performed and comments added to the results by laboratory staff when appropriate. DESIGN: Descriptive. METHOD: In the eastern South Limburg region 155 general practitioners received a list of 10 fictitious patient cases, each involving the possible addition of a specific test. The general practitioners could choose what they preferred the laboratory to do: add tests, phone the general practitioner, add a written comment or do nothing. In addition the general practitioners were asked to judge the effect of additional tests and comments on patient management with respect to diagnosis, treatment and referral, using 200 laboratory reports from their own patients. RESULTS: The response to the fictitious cases was 45%. Most general practitioners favoured the laboratory taking the initiative by adding on tests and commenting on the results in the given clinical scenarios. 78% of the questionnaires accompanying the lab reports were returned by 87% of the general practitioners. In nearly all cases (99%) the service was marked as useful. In more than half of the cases (53%) reflective testing affected the measures taken by the general practitioners. CONCLUSION: Reflective testing was in general welcomed by the general practitioners. In the majority of cases this led to an improvement in the diagnosis or adjustment of treatment.

The influence of six cardiovascular polymorphisms on a first event of ischemic heart disease is modified by sex and age.

OBJECTIVE: To examine the contribution of six cardiovascular polymorphisms to the occurrence of a first event of ischemic heart disease (IHD) in a primary care population with a high prevalence of hypertension. Furthermore, we specified the data for sex and age. METHODS: In this cross sectional case-control study, patients with a first event of IHD (157) and event-free controls (571) were studied. Both the groups were genotyped for the angiotensin II type 1 receptor (A1166C), angiotensinogen (M235 T), angiotensin converting enzyme (4656rpt), endothelial nitric oxide synthase (E298D), G-protein beta3 subunit (C825 T), and alpha-adducin (G460W) polymorphisms. Univariate and multivariate odds ratios (ORs) were calculated to assess the association between a first ischemic event and these polymorphisms. Sliding mean analyses were performed to show age-specific associations. RESULTS: Multivariate ORs indicated a protective association for the carrier status of the T-allele of AGT, overall [OR = 0.69 (0.34-0.90)] and for males [OR = 0.58 (0.27-0.89)]. Sliding mean analyses showed a continuous protective association with IHD of the T-allele of AGT with increasing age in males, whereas in females an increased risk for IHD was observed with a maximum OR of 1.6 at the age of 56 years. CONCLUSION: In this population the T-allele of the AGT polymorphism is protective for a first event of IHD in males.

Sex-specific effect of the alpha-adducin (G460W) and AGTR1 (A1166C) polymorphism on carotid intima-media thickness.

OBJECTIVE: In a primary care population covering a broad spectrum of cardiovascular risk (HIPPOCRATES project) the relationship between carotid intima-media thickness (CIMT) and six cardiovascular polymorphisms were analyzed in a cross-sectional study. METHODS: CIMT was assessed in 618 participants, who were genotyped for the AGTR1 (A1166C), AGT (M235T), ACE (4656(rpt)), NOS3 (E298D), GNB3 (C825T) and ADD1 (G460W) polymorphisms. Linear regression analyses were performed to assess the relationship between CIMT and the polymorphisms. RESULTS: The study population included 289 men (46.8%) and 329 (53.2%) women of whom 52.3% were treated with cardiovascular medication. CIMT was significantly associated with age, female sex, use of cardiovascular medication, waist circumference and dyslipidemia. After correction for these covariates, multivariate linear regression analyses showed that only in women the C-allele of AGTR1 was associated with a thicker CIMT (P = 0.03). The T-allele of ADD1 was associated with a smaller CIMT in both men and women, but this only reached statistical significance in women (P = 0.03). CONCLUSION: Although the effect of both genetic variants on CIMT was small, this study showed a statistically significant effect of AGTR1 and ADD1 in women. However, our findings should be viewed as hypothesis-generating and require further confirmation in prospective epidemiological primary care studies.

The association between arterial stiffness and the angiotensin II type 1 receptor (A1166C) polymorphism is influenced by the use of cardiovascular medication.

OBJECTIVE: To examine in a population with a high prevalence of hypertension, the association between six cardiovascular polymorphisms, arterial stiffness and medication use. METHODS: In this cross-sectional study (Hypertension: Interaction and Prevalence of POlymorphisms related to Cardiovascular Risk and the Association to Treatment Efficacy Study project), arterial stiffness was assessed by measuring pulse wave velocity (PWV) in 575 patients in one primary care practice. Patients were genotyped for the angiotensin II type 1 receptor [AGTR1 (A1166C)], angiotensinogen (M235T), angiotensin-converting enzyme (4656rpt), endothelial nitric oxide synthase (E298D), G-protein beta3 (C825T), and alpha-adducin (G460W) polymorphisms. Linear regression analyses were performed to assess the association between polymorphisms and PWV. RESULTS: Thirty percent of the patients (273 men, 302 women) had a carotid-femoral pulse wave velocity above 12 m/s and more than 60% of the patients had a carotid-femoral/carotid-radial PWV (CF/CR ratio) above 1. The CF/CR ratio was significantly associated with age, sex, dislipidemia, cardiovascular medication use and pulse pressure. After correction for these covariates, multivariate linear regression analyses showed that the C allele of AGTR1 was associated with a lower CF/CR ratio. This association was significantly influenced by cardiovascular medication use (P = 0.011), and showed a dose-allele effect, the CF/CR ratio decreasing with the number of C alleles (P = 0.04). CONCLUSION: In a primary care population, this study showed an independent protective dose-allele effect for the presence of C alleles of the AGTR1 polymorphism on PWV. This association, which was influenced by the use of cardiovascular medication, needs further investigations to identify the underlying mechanisms.

Effects of ACE I/D and AT1R-A1166C polymorphisms on blood pressure in a healthy normotensive primary care population: first results of the Hippocates study.

BACKGROUND: Several studies have assessed the relationship between the angiotensin-converting enzyme (ACE) I/D or angiotensin II type 1 receptor (AT(1)R)-A C polymorphisms and blood pressure (BP). Since most data have been obtained in selected populations, the present study was performed in a healthy normotensive primary care population. OBJECTIVE: To investigate the individual effects of the aforementioned polymorphisms and their interaction on BP. METHODS: This cross-sectional study included 198 healthy subjects. Office BP was measured and polymorphisms were genotyped (polymerase chain reaction). Polymorphism interaction was tested using the following model: systolic blood pressure (SBP) (or diastolic blood pressure, DBP) = b(0)+ b(1)X + b(2)Y + b(3)XY, in which X and Y represent the polymorphisms' risk alleles. RESULTS: The ACE I/D polymorphism was associated with SBP (P = 0.002) and DBP (P = 0.004); highest pressures tracked with the DD genotype. Furthermore, in multiple linear regression analysis the ACE D allele was associated with SBP (P = 0.005) and DBP (P = 0.001), when adjusted for body mass index (BMI) and age. With respect to the AT(1)R-A C polymorphism, SBP was highest in the CC genotype (P = 0.025). In linear regression analysis the C allele was not associated with SBP. No synergistic effect of ACE D and AT(1)R C alleles on BP was found. Nevertheless, highest DBP tracked with the DDCC combination in comparison with other homozygous allele combinations (P = 0.030). CONCLUSIONS: This study confirmed an association of ACE I/D and AT(1)R-A C polymorphisms with BP in a healthy normotensive primary care population. Although synergistic effect of both polymorphisms on BP does not seem to be present, an additive effect on DBP is likely.