The socio-colonial history of Surinamese surnames applied to a validated surname list to identify ancestry in health research.

Around half of the population of Suriname, who are mainly of African and South Asian descent, migrated to the Netherlands at the end of the previous century, where they face higher perinatal and maternal mortality and up to 5 years lower life expectancy than European-Dutch. Analyses by ancestry are needed to address these inequalities, but the law prohibits registration by ancestry. Therefore, a list of Surinamese surnames was compiled and validated to identify the largest groups, African-Surinamese or South Asian-Surinamese ancestry in health research. A complete database of Surinamese surnames was provided by the National Population Registry of Suriname. Surname recognition by researchers of Surinamese ancestry was used. Disagreement was resolved using historical registers and through discussion. The list was further validated against contemporary lists of Surinamese surnames with self-defined ancestry, obtained during population and clinical studies in Suriname and the Netherlands. All 71,529 Surinamese surnames were encoded, as African-Surinamese (34%), South Asian-Surinamese (18%), Brazilian or other Iberian (17%), Indonesian-Surinamese (13%), Chinese-Surinamese (5%), First Nation (2%), and other (10%). Compared to self-defined ancestry, South Asian-Surinamese surname coding had 100% sensitivity, 99.8% specificity, and 99.9% accuracy. For African-Surinamese, who may have Dutch surnames, these values depended on geocoding. With a known Surinamese origin, sensitivity, specificity, and accuracy were, respectively, 97.3%, 100%, and 98.6%, but without this information, there was interference of African-Surinamese with European-Dutch surnames in the Dutch validation sample. In conclusion, the Surinamese Surname List has a high accuracy in identifying persons of Surinamese ancestry. This quick, inexpensive, and nonintrusive method, which is unaffected by response bias, might be a valuable tool in public health research to help address the profound health disparities by ancestry.

Physical activity and obesity: is there a difference in association between the Asian- and African- Surinamese adult population?

OBJECTIVE: The role of different physical activity (PA) characteristics, i.e. domain, duration and intensity in obesity prevention still requires investigation. Furthermore, ethnicity can modify the effect of PA on body composition. Therefore, we aim to describe the association between obesity and PA characteristics across the Asian- and African-Surinamese population, living in the capital of Suriname. DESIGN: Between February 2013 and July 2015, we included 1157 healthy subjects, 18-70 years, from the Healthy Life in Suriname (HELISUR) study. We measured height, weight, hip and waist circumference and defined general and central obesity according to World Health Organization (WHO) recommendations. The International Physical Activity Questionnaire was used to assess PA and to calculate the duration (minutes/week) and the total volume (METs-minutes/week) of activity. Ethnicity was self-reported. RESULTS: Out of 1157 participants we included 1079 (42.6% Asian-Surinamese, 40.1% African-Surinamese and 17.3% of other ethnicity), mean age 42.6 ± 13.6 years for analysis. Obesity prevalence ratio (PR) was significantly lower in participants meeting WHO PA recommendations [PR= 0.81 (0.68-0.97)], especially within the commuting [PR= 0.66 (0.47-0.91)] and leisure time domains [PR= 0.67 (0.47-0.94)], compared to participants that did not meet the recommendations. Active minutes/week and total volume of activity were inversely associated with obesity and waist circumference, in the overall (p < 0.05) and in the African-Surinamese population (p < 0.05), but not in the Asian-Surinamese population. CONCLUSION: Meeting PA recommendations, particularly within the commuting and leisure time domains, is associated with lower obesity prevalence in the total population. Among the African-Surinamese population, PA within the leisure time domain, more active minutes/week and higher levels of total volume are associated with a lower obesity prevalence. This is not found in the Asian-Surinamese population.

The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC-Trial): A randomized controlled first-in-human trial.

AIMS: Increasing evidence indicates that the ATP-generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, it has been shown that beta-guanidinopropionic acid (GPA), a kidney-synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. To further develop the substance as a potential blood pressure-lowering agent, we assessed the tolerability of a sub-therapeutic GPA dose in healthy men. METHODS: In this active and placebo-controlled, triple-blind, single-centre trial, we recruited 24 healthy men (18-50 years old, BMI 18.5-29.9 kg m-2 ) in the Netherlands. Participants were randomized (1:1:1) to one week daily oral administration of GPA 100 mg, creatine 5 g, or matching placebo. The primary outcome was the tolerability of GPA, in an intent-to-treat analysis. RESULTS: Twenty-four randomized participants received the allocated intervention and 23 completed the study. One participant in the placebo arm dropped out for personal reasons. GPA was well tolerated, without serious or severe adverse events. No abnormalities were reported with GPA use in clinical safety parameters, including physical examination, laboratory studies, or 12-Lead ECG. At day 8, mean plasma GPA was 213.88 (SE 0.07) in the GPA arm vs. 32.75 (0.00) nmol l-1 in the placebo arm, a mean difference of 181.13 (95% CI 26.53-335.72). CONCLUSION: In this first-in-human trial, low-dose GPA was safe and well-tolerated when used during 1 week in healthy men. Subsequent studies should focus on human pharmacokinetic and pharmacodynamic assessments with different doses.

Assessing the feasibility of the Healthy Life in Suriname Study: using advanced hemodynamics to evaluate cardiovascular risk.

OBJECTIVES: To determine the feasibility of assessing population cardiovascular risk with advanced hemodynamics in the Healthy Life in Suriname (HELISUR) study. METHODS: This was a preliminary study conducted in May - June 2012 using the Technical-Economic-Legal-Operational-Scheduling (TELOS) method to assess the feasibility of the HELISUR-a large-scale, cross-sectional population study of cardiovascular risk factors and disease in Suriname. Suriname, a middle-income country in South America with a population of mostly African and Asian ethnicity, has a high risk of cardiovascular disease. A total of 135 volunteers 18 - 70 years of age participated. A health questionnaire was tested in a primary health care center, and non-invasive cardiovascular evaluations were performed in an academic health center. The cardiovascular evaluation included sitting, supine, and standing blood pressure, and intermediate endpoints, such as cardiac output, peripheral vascular resistance, pulse wave velocity, and augmentation index. RESULTS: The TELOS testing found that communicating by cellular phone was most effective for appointment adherence, and that completion of the questionnaire often required assistance from a trained interviewer; modifications to improve the clarity of the questions are recommended. Regarding the extended cardiovascular assessments of peripheral and central hemodynamics, the findings showed these to be technically and operationally feasible and well tolerated by participants, in terms of burden and duration. CONCLUSIONS: Findings of this feasibility assessment indicate that large-scale, detailed evaluations of cardiovascular risk, including a questionnaire and advanced central and peripheral hemodynamics, are feasible in a high-risk population in a middle-income setting.

Health literacy in Suriname.

BACKGROUND: Low health literacy is an independent predictor of cardiovascular mortality. However, data on health literacy in low- and middle-income countries are scarce. Therefore, we assessed the level of health literacy in Suriname, a middle-income country with a high cardiovascular mortality. METHODS: We estimated health literacy in a convenience sample at an urban outpatient center in the capital and at a semirural health center, using the validated Rapid Estimate of Adult Literacy in Medicine adapted for the Dutch language (REALM-D) instrument. REALM-D scores vary from 0 to 66 (all correct). The primary outcome was the level of health literacy. Furthermore, we assessed the effect of age, sex, ethnicity, disease history, research location, and level of education on health literacy with multivariable linear regression. RESULTS: We included 99 volunteers (52% men; 51% urban research location) with a mean age of 44.9 years (SD 13.4). The mean REALM-D score was moderate: 48.6 (SD 8.1). Greater health literacy was associated with male sex, an urban research location, and a higher educational level. CONCLUSION: Health literacy was moderate in these Surinamese participants. Health care workers should take health literacy into account, and targeted interventions should be developed to improve health literacy in Suriname.

Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and ß-adrenergic blockers? A systematic review.

BACKGROUND: Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to ß-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. METHODS: Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. RESULTS: We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and ß-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. CONCLUSION: Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs.

Arterial Hypertension in Women: State of the Art and Knowledge Gaps.

Hypertension is the leading risk factor for cardiovascular disease and premature death among women globally. However, there is a fundamental lack of knowledge regarding the sex-specific pathophysiology of the condition. In addition, risk factors for hypertension and cardiovascular disease unique to women or female sex are insufficiently acknowledged in clinical guidelines. This review summarizes the existing evidence on women and female-specific risk factors and clinical management of hypertension, to identify critical knowledge gaps relevant to research, clinical practice, and women's heart health awareness. Female-specific risk factors relate not only to reproduction, such as the association of gynecological conditions, adverse pregnancy outcomes or menopause with hypertension, but also to the specific roles of women in society and science, such as gender differences in received medical care and the underrepresentation of women in both the science workforce and as participants in research, which contribute to the limited evidence-based, gender- or sex-specific recommendations. A key point is that the development of hypertension starts in young, premenopausal women, often in association with disorders of reproductive organs, and therefore needs to be managed early in life to prevent future cardiovascular disease. Considering the lower blood pressure levels at which cardiovascular disease occurs, thresholds for diagnosis and treatment of hypertension may need to be lower for women.

The association of leisure-time physical activity and active commuting with measures of socioeconomic position in a multiethnic population living in the Netherlands: results from the cross-sectional SUNSET study.

BACKGROUND: In most European origin populations measures of socioeconomic position are positively associated with leisure time physical activity (LTPA), this is unclear for active commuting. In addition, these associations have scarcely been studied in ethnic minority groups, who often have a high cardiovascular disease risk. Because of the expected public health potential, we assessed the relationship of active commuting and LTPA with measures of socioeconomic position across two large ethnic minority groups in the Netherlands as compared to the European-Dutch population. METHODS: We included South Asian-Surinamese (n = 370), African-Surinamese (n = 689), and European-Dutch (n = 567) from the cross-sectional population-based SUNSET study (2001-2003). Active commuting and LTPA were assessed by the SQUASH physical activity questionnaire and calculated in square-root-transformed metabolic equivalents of task-hours/week (SQRTMET). Socioeconomic position was indicated by level of education (low/high) and occupational class (low/high). We used age-adjusted linear regression models to assess the association between physical activity and socioeconomic position. RESULTS: Compared to the European-Dutch men, South Asian-Surinamese men engaged in lower levels of commuting activity and LTPA, and South Asian-Surinamese women engaged in lower levels of LTPA than their European-Dutch counterparts. Differences between the African Surinamese and the European-Dutch were small. We observed a positive gradient in active commuting activity for education in European-Dutch men (beta high education was 0.93, 95%CI: 0.45-1.40 SQRTMET higher versus low education), in South Asian-Surinamese men (beta: 0.56, 0.19-0.92), but not in African-Surinamese men (-0.06, -0.45-0.33, p for ethnicity-interaction = 0.002). In women we observed a positive gradient in active commuting activity and occupational class in European-Dutch women, and less strongly in South Asian-Surinamese and African-Surinamese women (p for ethnicity-interaction = 0.02). For LTPA and socioeconomic position, we observed no statistically significant interaction by ethnicity. CONCLUSIONS: The positive gradient for socioeconomic position observed in European-Dutch was less strong, in particular for active commuting, among the South Asian-Surinamese and the African-Surinamese. This indicates that the typical focus on physical activity interventions in lower socioeconomic groups could work for European-Dutch populations, but this strategy may not be entirely applicable in the ethnic minority groups.

Initial combination therapy for hypertension in patients of African ancestry: a systematic review and meta-analysis.

We systematically reviewed randomized controlled trials (RCTs) that consider the effect of initial dual antihypertensive combination treatment on blood pressure (BP), morbidity, or mortality in hypertensive African ancestry adults, using the methodology of the Cochrane Collaboration. Main outcomes were difference in means (continuous data) and risk ratio (dichotomous data).We retrieved 1728 reports yielding 13 RCTs of 4 weeks to 3 years duration (median 8 weeks) in 3843 patients. Systolic BP was significantly higher on ß-adrenergic blocker vs. other combinations, 3.80 [0.82;6.78] mmHg, but comparable for other combinations. Hypokalemia and hyperglycemia occurred with calcium channel blocker (CCB) + diuretics > diuretics + angiotensin converting enzyme inhibitor (ACEI)/angiotensin-II-type-1-receptor antagonist (ARB) > CCB + ACEI/ARB. An RCT including high-risk patients reported combined morbidity/mortality for hydrochlorothiazide (mg) 25 + benazepril 40 vs. amlodipine 10 + benazepril 40 of respectively 8.9% vs. 6.6% (n = 1414, risk ratio 1.35 [0.94;1.94]; all patients, N = 11 506, 1.23 [1.11;1.37]).We conclude that limited evidence supports CCB + ACEI rather than HCT + ACEI as first-line initial combination therapy in African ancestry patients with hypertension. PROSPERO: CRD42021238529.

Lifetime prevalence and correlates of syncope in five ancestry groups. The HELIUS study.

Aim: To explore the lifetime prevalence and correlates of syncope in the general population. Methods: Through stratified random sampling, we included 14,937 White-European, Asian, Turkish, Moroccan, and West-African ancestry adults (18-70 y) in the cross-sectional Healthy Life in an Urban Setting (HELIUS) population study. We assessed syncope history by ancestry, and the potential correlates body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP), resting plasma activity of creatine kinase (CK), the ATP-generating enzyme that facilitates cardiovascular contractility and sodium retention, and in a subgroup, supine cardiac contractility (dP/dt), cardiac output (CO) and systemic vascular resistance (SVR). Results: Mean age of the participants (39% men) was 43.3 y (SD12.9). Lifetime prevalence of syncope in women/men was respectively (%), White-European 42/24; Asian 34/19; Moroccan 32/16; Turkish 30/17; and West-African 20/14. Mean age at first syncope was 24 y (SD13). Participants with syncope history had lower SBP, DBP, BMI, CK, and modestly lower dP/dt and CO, but not SVR. In multivariable regression analysis, male sex (OR 0.52 [0.48 to 0.57]), West-African ancestry (0.59 [0.54 to 0.65]), and CK (0.56 [0.46 to 0.69]/log CK increase) were negatively associated with syncope. Conclusion: This study indicates that West-African ancestry, male sex, and high activity of the pressor enzyme CK are associated with lower syncope prevalence. These findings may inform further studies on the hemodynamics of syncope.

Health Professionals' Perceptions of Disparities in Hypertension Control: A Mixed Methods Study.

BACKGROUND: Health professionals' commitment is needed to address disparities in hypertension control by ancestry, but their perceptions regarding these disparities are understudied. METHODS: Cross-sectional mixed methods study in a universal healthcare setting in the Netherlands. Snowball sampling was used to include professionals practicing in a large multicity conglomerate including the capital city. Online surveys were collected, and survey participants were randomly selected for in-depth interviews. We used quantitative and qualitative methods to analyze health professionals' awareness, beliefs, and possible interventions regarding these disparities. RESULTS: We analyzed questionnaire data of 77 health professionals (medical doctors n = 70, nurses = 7), whereas 13 were interviewed. Most professionals were women (59%), general practitioners (81%); and White-European (77%), with 79% caring for patients of diverse ancestry. Disparities in hypertension control by ancestry were perceived to exist nationally (83% [95% CI, 75;91]), but less so in health professionals' own clinics (62% [52;73]), or among their own patients (56% [45;67]). Survey respondents emphasized patient rather than provider-level factors as mediators of poor hypertension control by ancestry. The collection of data on patients' ancestry, updating guidelines, and professional training were considered helpful to reduce disparities. Interviewees further emphasized patient-level factors, but also the need to better educate health professionals and increase their awareness. CONCLUSIONS: This explorative study finds that health professionals predominantly attribute disparities in hypertension control to patient-level factors. Awareness of disparities was lower for more proximate healthcare settings. These data emphasize the need to consider health professionals' perceptions when addressing disparities in hypertension control.

Creatine and creatine analogues in hypertension and cardiovascular disease.

BACKGROUND: The creatine kinase system, the central regulatory system of cellular energy metabolism, provides ATP in situ at ATP-ases involved in ion transport and muscle contraction. Furthermore, the enzyme system provides relative protection from tissue ischaemia and acidosis. The system could therefore be a target for pharmacologic intervention. OBJECTIVES: To systematically evaluate evidence regarding the effectiveness of interventions directly targeting the creatine kinase system as compared to placebo control in adult patients with essential hypertension or cardiovascular disease. SEARCH METHODS: Electronic databases searched: Medline (1950 - Feb 2011), Embase (up to Feb 2011), the Cochrane Controlled Trials Register (issue 3, Aug 2009), Latin-American/Caribbean databank Lilacs; references from textbooks and reviews; contact with experts and pharmaceutical companies; and searching the Internet. There was no language restriction. SELECTION CRITERIA: Randomized controlled trials comparing creatine, creatine phosphate, or cyclocreatine (any route, dose or duration of treatment) with placebo; in adult patients with essential hypertension, heart failure, or myocardial infarction. We did not include papers on the short-term use of creatine during cardiac surgery. DATA COLLECTION AND ANALYSIS: The outcomes assessed were death, total myocardial infarction (fatal or non-fatal), hospitalizations for congestive heart failure, change in ejection fraction, and changes in diastolic and systolic blood pressure in mm Hg or as percent change. MAIN RESULTS: Full reports or abstracts from 1164 papers were reviewed, yielding 11 trials considering treatment with creatine or creatine analogues in 1474 patients with heart failure, ischemic heart disease or myocardial infarction. No trial in patients with hypertension was identified. Eleven trials (1474 patients, 35 years or older) comparing add-on therapy of the creatine-based drug on standard treatment to placebo control in patients with heart failure (6 trials in 1226 / 1474 patients ), or acute myocardial infarction (4 trials in 220 / 1474 patients) or 1 in ischemic heart disease (28 / 1474 patients) were identified. The drugs used were either creatine, creatine phosphate (orally, intravenously, or intramuscular) or phosphocreatinine. In the trials considering heart failure all three different compounds were studied; creatine orally (Gordon 1995, Kuethe 2006), creatine phosphate via intravenous infusion (Ferraro 1996, Grazioli 1992), and phosphocreatinine orally (Carmenini 1994, Maggi 1990). In contrast, the acute myocardial infarction trials studied intravenous creatine phosphate only. In the ischemic heart disease trial (Pedone 1984) creatine phosphate was given twice daily through an intramuscular injection to outpatients and through an intravenous infusion to inpatients. The duration of the study intervention was shorter for the acute patients, from a two hour intravenous infusion of creatine phosphate in acute myocardial infarction (Ruda 1988, Samarenko 1987), to six months in patients with heart failure on oral phosphocreatinine therapy (Carmenini 1994). In the acute myocardial infarction patients the follow-up period varied from the acute treatment period (Ruda 1988) to 28 days after start of the symptoms (Samarenko 1987) or end of the hospitalization period (Zochowski 1994). In the other trials there was no follow-up after discontinuation of treatment, except for Gordon 1995 which followed the patients until four days after stopping the intervention.Only two out of four trials in patients with acute myocardial infarction reported mortality outcomes, with no significant effect of creatine or creatine analogues (RR 0.73, CI: 0.22 - 2.45). In addition, there was no significance on the progression of myocardial infarction or improvement on ejection fraction. The main effect of the interventions seems to be on improvement of dysrhythmia. AUTHORS' CONCLUSIONS: This review found inconclusive evidence to decide on the use of creatine analogues in clinical practice. In particular, it is not clear whether there is an effect on mortality, progression of myocardial infarction and ejection fraction, while there is some evidence that dysrhythmia and dyspnoea might improve. However, it is not clear which analogue, dose, route of administration, and duration of therapy is most effective. Moreover, given the small sample size of the discussed trials and the heterogeneity of the population included in these reports, larger clinical studies are needed to confirm these observations.

African Ancestry vs. Creatine Kinase to Predict Hypertension Control: Time for a Change?

BACKGROUND: African ancestry patients are considered separately in hypertension guidelines because of more severe hypertension that is presumably harder to control. However, despite the perceived benefit in reducing health disparities, racial profiling in medicine is increasingly criticized for its potential of bias and stereotyping. Therefore, we studied whether creatine kinase (CK), an ATP-regenerating enzyme that enhances vascular contractility and sodium retention, could serve as a more proximate causal parameter of therapy failure than race/ancestry. METHODS: In a random multiethnic population sample, we compared the performance of African ancestry vs. resting plasma CK as predictors of treated uncontrolled hypertension. Difference in area under the receiver operating curve (AUC) was the primary outcome. RESULTS: We analyzed 1,405 persons of African, Asian, and European ancestry (40.2% men, mean age 45.5 years, SE 0.2). Hypertension prevalence was 39% in African vs. 29% in non-African ancestry participants vs. 41% and 27% by high and low CK tertiles. Control rates of treated patients were similar by ancestry (African ancestry patients 40%, non-African ancestry 41%; P = 0.84), but 27% vs. 53% in patients with high vs. low CK (22% vs. 67% in African and 32% vs. 52% in non-African participants). AUC was 0.51 [0.41-0.60] for African ancestry vs. 0.64 [0.55-0.73] for log CK (P = 0.02). CONCLUSIONS: In contrast to African ancestry, CK might identify hypertensive patients at risk for therapy failure across different ancestry groups. Larger, prospective studies should establish whether resting plasma CK is clinically useful as an impartial method to help predict antihypertensive therapy failure.

Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex.

Hypertension is associated with chronic vascular inflammation. We tested the hypothesis that the sensitivity to develop hypertension and vascular remodeling depends on the immunological background. Blood pressure, vascular remodeling, endothelial function, vascular architecture (number of collateral arteries), and expression of inflammatory cytokines were determined in mice that received N(G)-nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthesis. We studied C57BL/6, BALB/c, and BALB.B6-Cmv1r mice, a congenic strain where the natural killer (NK) gene complex of C57BL/6 mice is introduced in the BALB/c background. During a 4-wk treatment with l-NAME, blood pressure initially increased in both C57BL/6 and BALB/C mice, but after 4 wk, only C57BL/6 mice showed a significant increase in mean arterial blood pressure (+53 mmHg; P < 0.001) and small artery inward remodeling. Endothelial function and vascular design were significantly different between C57BL/6 mice and BALB/C mice. The inflammatory response was similar in C57BL/6 and BALB/C mice, except for the leukocyte marker CD11b. Cellular colocalization of CD11b with NK1.1 indicated the recruitment of NK cells in C57BL/6 mice. Congenic BALB.B6-Cmv1r mice showed the same endothelial response and vascular architecture as BALB/c mice. However, BALB.B6-Cmv1r mice displayed a similar sensitivity to hypertension and vascular remodeling as C57BL/6 mice. In conclusion, we have identified the NK gene complex as an important determinant in the genetically determined sensitivity to develop l-NAME-induced hypertension in mice.

CK (Creatine Kinase) Is Associated With Cardiovascular Hemodynamics: The HELIUS Study.

The ATP-regenerating enzyme CK (creatine kinase) is strongly associated with blood pressure, which lowers upon experimental CK inhibition. The enzyme is thought to affect cardiovascular hemodynamics through enhanced systemic vascular resistance, stroke volume, and cardiac contractility, but data on these parameters are lacking. We hereby report hemodynamics by CK levels in the multiethnic, cross-sectional HELIUS study (Healthy Life in an Urban Setting). Physical examination included sitting brachial blood pressure and noninvasively assessed supine systemic vascular resistance, stroke volume, cardiac output, and cardiac contractility, which we associated with resting plasma CK. Data from 14 937 men and women (mean age, 43.3; SD, 12.9) indicated that per log CK increase, blood pressure increased with 20.2 (18.9-21.4) mm Hg systolic/13.0 (12.2-13.7) diastolic, an odds ratio for hypertension of 6.1 (5.1-7.2). Outcomes were similar by sex, body mass index, and ancestry, although higher blood pressures in men, with overweight/obesity, and West-African ancestry were partially explained by higher CK, with an adjusted increase in systolic/diastolic pressure of 10.5 (10.0-10.9)/6.4 (6.0-6.7) mm Hg per log CK increase. Systemic vascular resistance, stroke volume, cardiac output, and cardiac contractility (n=7876), increased by respectively 20%, 39%, 14%, and 23% SD per log CK increase. This study indicates that the association of CK with blood pressure likely results from an increase in systemic vascular resistance and stroke volume. These data expand the knowledge on the nature of hypertension associated with CK and may inform further experiments on CK inhibition as a means to lower blood pressure.

Aortic pulse wave velocity in individuals of Asian and African ancestry: the HELISUR study.

Aortic pulse wave velocity has emerged as an important predictor of cardiovascular events, but data on ethnic differences in pulse wave velocity remain scarce. We explored differences in pulse wave velocity between people of Asian and African ancestry. Data were used from the cross-sectional Healthy Life in Suriname (HELISUR) study. Pulse wave velocity was estimated oscillometrically with the Arteriograph. We included 353 Asians and 364 Africans, aged respectively 44.9 (SD 13.5) and 42.8 (SD 14.1) years (p = 0.05). Crude median PWV was higher in Asians than in Africans (8.1 [IQR 6.9-10.1] m/s vs. 7.7 [IQR 6.5-9.3] m/s, p = 0.03), which was mainly attributable to an increased PWV in Asians ≥ 50 years (10.1 [IQR 8.7-11.8] m/s vs. 9.1 [IQR 7.9-11.3] m/s in Africans ≥50 years, p < 0.01). After adjustment for age and MAP in multivariable linear regression, Asians had a 1.044 [95% CI 1.019-1.072] m/s higher PWV compared to Africans. Additional adjustment for sex, glucose, total cholesterol, HDL cholesterol, triglycerides, BMI, and waist circumference did not substantially change the difference in pulse wave velocity between Asians and Africans (+1.044 [95% CI 1.016-1.074] m/s for Asians vs. Africans). In conclusion, persons of Asian ancestry have a higher pulse wave velocity than those of African ancestry. This persisted after adjustment for important cardiovascular risk parameters, including age and blood pressure. The higher PWV found in Asians could be consistent with their increased coronary heart disease risk.

Low creatine kinase is associated with a high population incidence of fainting.

OBJECTIVE: Vasoconstrictor capacity, skeletal muscle tone, and renal sodium retention are involved in the pathogenesis of fainting. As muscle contractility and ion transport are highly energy-demanding processes, we hypothesized that a low activity of the energy-generating enzyme creatine kinase (CK) is associated with a higher risk of fainting. The aim of this observational study was to explore the association of vasovagal syncope with low CK. METHODS: A random sample of 1,000 subjects aged 34-60 years was drawn from the general population, with 442 subjects eventually included in the study. Data on fainting history were collected with the investigators blinded to participants' CK level. We prepared this report according to the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) statement. The main outcome was the lifetime cumulative incidence of vasovagal syncope in subjects with low versus high-normal serum CK after a 3 days rest. RESULTS: The proportion of fainters within the high CK group was 29 out of 130 (22%) versus 121 out of 312 (39%) in the low CK group; a 73% greater occurrence of fainting with low CK (P = 0.0005). This finding was consistent across recurrent fainters, and in men and women. INTERPRETATION: Low CK is associated with a 73% higher incidence of fainting in a random population sample. The association is biologically plausible, as CK enhances cardiovascular and skeletal muscle contractility and salt retention. The presented data suggest that low CK activity is a potential new risk factor for vasovagal syncope.

Underuse of hydralazine and isosorbide dinitrate for heart failure in patients of African ancestry: a cross-European survey.

AIMS: Population data indicate that one in 25 persons of African ancestry has heart failure, a condition with relatively high mortality of around 50% in 5 years. Combined hydralazine and isosorbide dinitrate added to conventional therapy in African ancestry patients with heart failure and reduced ejection fraction improves quality of life and reduces the rate of first hospitalization for heart failure by 33% and annual mortality by 43%. The objectives of this study were to quantify the use of this guideline-recommended therapy in Europe and the potential effect of implementation gaps on mortality. METHODS AND RESULTS: Prescription drug registration and utilization databases and population statistics were analysed in a cross-European survey without language restriction. Main outcomes were the number of unique patients prescribed the fixed combination hydralazine-isosorbide dinitrate (primary) or both drugs (secondary) in Europe in 2015, and the excess mortality related to prescribing practices was estimated. The survey indicates that around 12 million persons of African ancestry live in Europe. It is estimated that 480 000 persons of this population group have heart failure, with 120 000 eligible for hydralazine and isosorbide dinitrate therapy. However, single-pill hydralazine-isosorbide dinitrate is not authorized and therefore not dispensed in Europe in 2015. Out of the 25 European nations surveyed, the UK and the Netherlands are the only countries with major African ancestry populations where both hydralazine and isosorbide dinitrate are available for oral use, aside Norway, Sweden, and Finland. Hydralazine and isosorbide dinitrate are prescribed to <500 European patients in 2015. Thus, despite the recommendations of the European Society of Cardiology, the large majority of African-European patients with heart failure do not receive this drug combination, potentially resulting in 4800 to 5800 excess deaths yearly. CONCLUSIONS: The life-saving, guideline-recommended, adjunctive therapy for heart failure in African ancestry patients with hydralazine and isosorbide dinitrate is rarely used in Europe. This major evidence-practice gap should urgently be overcome to reduce excess mortality in African-European patients with heart failure.