Genetic factors are relevant and independent determinants of antihypertensive drug effects in a multiracial population.

BACKGROUND: The success of antihypertensive drugs may be improved by better prediction of their efficacy in individual patients. The objective of our study was to determine whether genetic variation predicts the individual systolic blood pressure (SBP) response to antihypertensive drugs and to assess to what extent the individual treatment response could be explained by the combined effects of known demographic, environmental, and genetic factors. METHODS: A population-based, crossover, open-label randomized treatment study stratified for ethnicity in 102 mildly hypertensive patients aged 35-60 years in an outpatient hypertension clinic (the ROTATE study). Patients underwent five successive 6-week treatment episodes of single-drug treatment in a randomized order with representatives of the major antihypertensive drug classes. The primary outcome measure was the DeltaSBP after 6-week drug therapy. RESULTS: Participants (n = 97) completed 407 treatment episodes. The estimated unpredictable natural variation of SBP within individuals was 65% of the total study variance. The primary analysis model that considered the effects of environmental, demographic, and genetic factors and their interactions to SBP response to antihypertensive drugs, explained 23% of the total variance accounting for 66% of the predictable variance. Ethnicity, low sodium intake, and ADD1 614G-->T polymorphism were the only drug-related predictors. A number of genetic variants (ADD1 614G-->T, ADRB1 145A-->G, ADRB2 79C-->G, CYP11B2 -344C-->T, and SLC12A3 78G-->A) contributed significantly (9%) to the total variance of the SBP response. The contribution of each individual single-nucleotide polymorphism (SNP) ranged from 1.1 to 2.4%. CONCLUSIONS: Genetic factors are relevant and independent determinants of antihypertensive drug effects in a multiracial population.

Prevalence of diabetes mellitus and the performance of a risk score among Hindustani Surinamese, African Surinamese and ethnic Dutch: a cross-sectional population-based study.

BACKGROUND: While the prevalence of type 2 diabetes mellitus (DM) is high, tailored risk scores for screening among South Asian and African origin populations are lacking. The aim of this study was, first, to compare the prevalence of (known and newly detected) DM among Hindustani Surinamese, African Surinamese and ethnic Dutch (Dutch). Second, to develop a new risk score for DM. Third, to evaluate the performance of the risk score and to compare it to criteria derived from current guidelines. METHODS: We conducted a cross-sectional population based study among 336 Hindustani Surinamese, 593 African Surinamese and 486 Dutch, aged 35-60 years, in Amsterdam. Logistic regressing analyses were used to derive a risk score based on non-invasively determined characteristics. The diagnostic accuracy was assessed by the area under the Receiver-Operator Characteristic curve (AUC). RESULTS: Hindustani Surinamese had the highest prevalence of DM, followed by African Surinamese and Dutch: 16.7, 8.1, 4.2% (age 35-44) and 35.0, 19.0, 8.2% (age 45-60), respectively. The risk score included ethnicity, body mass index, waist circumference, resting heart rate, first-degree relative with DM, hypertension and history of cardiovascular disease. Selection based on age alone showed the lowest AUC: between 0.57-0.62. The AUC of our score (0.74-0.80) was higher than that of criteria from guidelines based solely on age and BMI and as high as criteria that required invasive specimen collection. CONCLUSION: In Hindustani Surinamese and African Surinamese populations, screening for DM should not be limited to those over 45 years, as is advocated in several guidelines. If selective screening is indicated, our ethnicity based risk score performs well as a screening test for DM among these groups, particularly compared to the criteria based on age and/or body mass index derived from current guidelines.

Distribution of creatine kinase in the general population: implications for statin therapy.

BACKGROUND: Eligible subjects with mildly elevated serum creatine kinase (CK) activity are often excluded before randomization in statin trials, but patients may potentially be misclassified as having hyperCKemia when inappropriate reference limits are used. Little information is usually given regarding how reference limit data were established, although evidence suggests that the variation of CK activity in the general population is wider than reflected in reference intervals in current use. METHODS: We determined reference intervals for serum CK according to National Committee on Clinical Laboratory Standards/Nordic Reference Interval Project guidelines, in a stratified random sample of the population, including 1444 individuals, aged 34 to 60 years, after 3 days of rest. Participants were mainly of white European (n = 503), South Asian (n = 292), or African descent (n = 580). RESULTS: The calculated upper reference limits (97.5th percentile) for nonblack and black women and men were 2 to 5 times higher than recommended by the assay manufacturer. Respectively 13% of the white Europeans, 23% of South Asians, and 49% of the black people had serum CK activities above the manufacturer-provided limits. CONCLUSION: The variation in CK activity within the population is wider than previously suggested in smaller, nonrandom samples, and relatively high values occur frequently in all subgroups studied after rest. Therefore, we infer that upward adjustment of the upper reference limit is necessary for all population subgroups studied. The use of appropriately established reference intervals may improve the use of statins and particularly benefit the control of dyslipidemia in those with relatively high baseline CK activity.

Creatine kinase activity is associated with blood pressure.

BACKGROUND: We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular contraction, and antagonizes nitric oxide-mediated functions. Relatively high activity of the enzyme, particularly in resistance arteries, is thought to enhance pressor responses and increase blood pressure. Tissue creatine kinase activity is reported to be high in black people, a population subgroup with greater hypertension risk; the proposed effects of high creatine kinase activity, however, are not "race dependent." We therefore assessed whether creatine kinase is associated with blood pressure in a multiethnic population. METHODS AND RESULTS: We analyzed a stratified random sample of the population of Amsterdam, The Netherlands, consisting of 1444 citizens (503 white European, 292 South Asian, 580 black, and 69 of other ethnicity) aged 34 to 60 years. We used linear regression analysis to investigate the association between blood pressure and normal serum creatine kinase after rest, as a substitute measure of tissue activity. Creatine kinase was independently associated with blood pressure, with an increase in systolic and diastolic pressure, respectively, of 8.0 (95% CI, 3.3 to 12.7) and 4.7 (95% CI, 1.9 to 7.5) mm Hg per log creatine kinase increase after adjustment for age, sex, body mass index, and ethnicity. CONCLUSIONS: Creatine kinase is associated with blood pressure. Further studies are needed to explore the nature of this association, including how variation in cardiovascular creatine kinase activity may affect pressor responses.

Prevalence, awareness, treatment, and control of hypertension among Black Surinamese, South Asian Surinamese and White Dutch in Amsterdam, The Netherlands: the SUNSET study.

OBJECTIVE: To assess ethnic differences in prevalence, levels of awareness, treatment and control of hypertension among Dutch ethnic groups and to determine whether these differences are consistent with the UK findings. DESIGN: Cross-sectional survey. SETTING: South-east Amsterdam, The Netherlands. PARTICIPANTS: A random sample of 1383 non-institutional adults aged 35-60 years. Of these, 36.7% were White, 42% were Black and 21.3% were South Asian people. MAIN OUTCOME MEASURES: Prevalence of hypertension, rates of awareness, treatment, and control of hypertension. RESULTS: The Black and South Asian subjects had a higher prevalence of hypertension compared with White people. After adjustments for age, the odds ratios (95% confidence interval) for being hypertensive were 2.2 (1.4-3.4; P < 0.0001) and 3.8 (2.6-5.7; P < 0.0001) for Black men and women, respectively, and 1.7 (1.0-2.6; P = 0.039) and 2.8 (1.8-4.5; P < 0.0001) for South Asian men and women, compared with White people. There were no differences in awareness and pharmacological treatment of hypertension between the groups. However, Black hypertensive men 0.3 (0.1-0.7; P < 0.01) and women 0.5 (0.3-0.9; P < 0.05) were less likely to have their blood pressure adequately controlled compared with White people. CONCLUSION: The higher prevalence of hypertension found among Black and South Asian people in The Netherlands is consistent with the UK studies. However, the lower control rates and the similar levels of awareness and treatment of hypertension in Black Surinamese contrast with the higher rates reported in African Caribbeans in the UK. The rates for the South Asians in The Netherlands were relatively favourable compared to similar South Asian groups in the UK. These findings underscore the urgent need to develop strategies aimed at improving the prevention and control of hypertension, especially among Black people, in The Netherlands.