Feasibility and antihypertensive effect of replacing regular salt with mineral salt -rich in magnesium and potassium- in subjects with mildly elevated blood pressure

<p>Abstract</p> <p>Background</p> <p>High salt intake is linked to hypertension whereas a restriction of dietary salt lowers blood pressure (BP). Substituting potassium and/or magnesium salts for sodium chloride (NaCl) may enhance the feasibility of salt restriction and lower blood pressure beyond the sodium reduction alone. The aim of this study was to determine the feasibility and effect on blood pressure of replacing NaCl (Regular salt) with a novel mineral salt [50% sodium chloride and rich in potassium chloride (25%), magnesium ammonium potassium chloride, hydrate (25%)] (Smart Salt).</p> <p>Methods</p> <p>A randomized, double-blind, placebo-controlled study was conducted with an intervention period of 8-weeks in subjects (n = 45) with systolic (S)BP 130-159 mmHg and/or diastolic (D)BP 85-99 mmHg. During the intervention period, subjects consumed processed foods salted with either NaCl or Smart Salt. The primary endpoint was the change in SBP. Secondary endpoints were changes in DBP, daily urine excretion of sodium (24-h dU-Na), potassium (dU-K) and magnesium (dU-Mg).</p> <p>Results</p> <p>24-h dU-Na decreased significantly in the Smart Salt group (-29.8 mmol; p = 0.012) and remained unchanged in the control group: resulting in a 3.3 g difference in NaCl intake between the groups. Replacement of NaCl with Smart Salt resulted in a significant reduction in SBP over 8 weeks (-7.5 mmHg; p = 0.016). SBP increased (+3.8 mmHg, p = 0.072) slightly in the Regular salt group. The difference in the change of SBP between study groups was significant (p < 0.002).</p> <p>Conclusions</p> <p>The substitution of Smart Salt for Regular salt in subjects with high normal or mildly elevated BP resulted in a significant reduction in their daily sodium intake as well as a reduction in SBP.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN01739816">ISRCTN01739816</a></p

Change in antihypertensive drug prescribing after guideline implementation: a controlled before and after study

<p>Abstract</p> <p>Background</p> <p>Antihypertensive drug choices and treatment levels are not in accordance with the existing guidelines. We aimed to assess the impact of a guideline implementation intervention on antihypertensive drug prescribing.</p> <p>Methods</p> <p>In this controlled before and after study, the effects of a multifaceted (education, audit and feedback, local care pathway) quality programme was evaluated. The intervention was carried out in a health centre between 2002 and 2003. From each health care unit (n = 31), a doctor-nurse pair was trained to act as peer facilitators in the intervention.</p> <p>All antihypertensive drugs prescribed by 25 facilitator general practitioners (intervention GPs) and 53 control GPs were retrieved from the nationwide Prescription Register for three-month periods in 2001 and 2003. The proportions of patients receiving specific antihypertensive drugs and multiple antihypertensive drugs were measured before and after the intervention for three subgroups of hypertension patients: hypertension only, with coronary heart disease, and with diabetes.</p> <p>Results</p> <p>In all subgroups, the use of multiple concurrent medications increased. For intervention patients with hypertension only, the odds ratio (OR) was 1.12 (95% CI 0.99, 1.25; p = 0.06) and for controls 1.13 (1.05, 1.21; p = 0.002). We observed no statistically significant differences in the change in the prescribing of specific antihypertensive agents between the intervention and control groups. The use of agents acting on the renin-angiotensin-aldosterone system increased in all subgroups (hypertension only intervention patients OR 1.19 (1.06, 1.34; p = 0.004) and controls OR 1.24 (1.15, 1.34; p < 0.0001).</p> <p>Conclusions</p> <p>A multifaceted guideline implementation intervention does not necessarily lead to significant changes in prescribing performance. Rigorous planning of the interventions and quality projects and their evaluation are essential.</p

Are coronary event rates declining slower in women than in men – evidence from two population-based myocardial infarction registers in Finland?

<p>Abstract</p> <p>Background</p> <p>Studies have suggested that the prevention and treatment of coronary heart disease may not have been as effective in women as in men. Therefore, we aimed to examine whether the incidence, attack rate and mortality of myocardial infarction (MI) events have declined less in women than in men.</p> <p>Methods</p> <p>Two large population-based MI registers, the FINAMI register and the Finnish Cardiovascular Disease Register (CVDR) were used for comparing the event rates among men and women aged ≥35 years in two time periods, 1994–1996 and 2000–2002.</p> <p>Results</p> <p>In the FINAMI register a total of 5,252 events were recorded in men and 4,898 in women. Corresponding numbers in the CVDR were 78,709 and 70,464. Both FINAMI and CVDR data suggested smaller declines in incidence and attack rate of MI events in women than in men. In CVDR data the decline in mortality was also smaller in women than in men, while in FINAMI data this difference did not reach statistical significance. In the large CVDR data set, negative binomial regression models revealed smaller declines in incidence (p = 0.006), attack rate (p = 0.008) and mortality (p = 0.04) in women than in men aged <55 years. In persons ≥55 years no difference was observed between women and men.</p> <p>Conclusion</p> <p>The incidence and attack rate of MI events have declined less in women aged <55 than in men of similar age. In older persons no significant differences were observed. Further studies are warranted to find out the reasons why the development has been less favourable for young women than for men.</p

Cost-effectiveness analysis of guidelines for antihypertensive care in Finland

<p>Abstract</p> <p>Background</p> <p>Hypertension is one of the major causes of disease burden affecting the Finnish population. Over the last decade, evidence-based care has emerged to complement other approaches to antihypertensive care, often without health economic assessment of its costs and effects. This study looks at the extent to which changes proposed by the 2002 Finnish evidence-based Current Care Guidelines concerning the prevention, diagnosis, and treatment of hypertension (the ACCG scenario) can be considered cost-effective when compared to modelled prior clinical practice (the PCP scenario).</p> <p>Methods</p> <p>A decision analytic model compares the ACCG and PCP scenarios using information synthesised from a set of national registers covering prescription drug reimbursements, morbidity, and mortality with data from two national surveys concerning health and functional capacity. Statistical methods are used to estimate model parameters from Finnish data. We model the potential impact of the different treatment strategies under the ACCG and PCP scenarios, such as lifestyle counselling and drug therapy, for subgroups stratified by age, gender, and blood pressure. The model provides estimates of the differences in major health-related outcomes in the form of life-years and costs as calculated from a 'public health care system' perspective. Cost-effectiveness analysis results are presented for subgroups and for the target population as a whole.</p> <p>Results</p> <p>The impact of the use of the ACCG scenario in subgroups (aged 40–80) without concomitant cardiovascular and related diseases is mainly positive. Generally, costs and life-years decrease in unison in the lowest blood pressure group, while in the highest blood pressure group costs and life-years increase together and in the other groups the ACCG scenario is less expensive and produces more life-years. When the costs and effects for subgroups are combined using standard decision analytic aggregation methods, the ACCG scenario is cost-saving and more effective.</p> <p>Conclusion</p> <p>The ACCG scenario is likely to reduce costs and increase life-years compared to the PCP scenario in many subgroups. If the estimated trade-offs between the subgroups in terms of outcomes and costs are acceptable to decision-makers, then widespread implementation of the ACCG scenario is expected to reduce overall costs and be accompanied by positive outcomes overall.</p

Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression

Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression

X-chromosome and kidney function:evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.</p

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd