Holly Kramer

Hypertension Treatment and Control in Five European Countries, Canada, and the United States

Abstract—Levels of hypertension treatment and control have been noted to vary between Europe and North America, although direct comparisons with similar methods have not been undertaken. In this study, we sought to estimate the relative impact of hypertension treatment strategies in Germany, Sweden, England, Spain, Italy, Canada, and the United States by using sample surveys conducted in the 1990s. Hypertension was defined as a blood pressure of 160/95 mm Hg or 140/90 mm Hg, plus persons taking antihypertensive medication. “Controlled hypertension” was defined as a blood pressure less than threshold among persons taking antihypertensive medications. Among persons 35 to 64 years, 66% of hypertensives in the United States had their blood pressure controlled at 160/95 mm Hg, compared with 49% in Canada and 23% to 38% in Europe. Similar discrepancies were apparent at the 140/90 mm Hg threshold, at which 29% of hypertensives in the United States, 17% in Canada, and ≤10% in European countries had their blood pressure controlled. At the 140/90 mm Hg cutpoint, two thirds to three quarters of the hypertensives in Canada and Europe were untreated compared with slightly less than half in the United States. Although guidelines vary among countries, resulting in different case definitions, this does not account entirely for the varying success of different national control efforts. Low treatment and control rates in Europe, combined with a higher prevalence of hypertension, could contribute to a higher burden of cardiovascular disease risk attributable to elevated blood pressure compared with that in North America.

Dyslipidemia Prevalence, Treatment, and Control in the Multi-Ethnic Study of Atherosclerosis (MESA) Gender, Ethnicity, and Coronary Artery Calcium

Background— To assess the implementation challenge facing the Third Report of the Adult Treatment Panel (ATP III) of the National Cholesterol Education Program, we determined the prevalence, treatment, and control of dyslipidemia, including ethnic and gender differences, in persons free of known clinical cardiovascular disease (CVD). In addition, this report provides information about the presence of coronary artery calcium (CAC) across groups defined by risk and recommendations for the use of lipid-lowering drugs. Methods and Results— The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study of 6814 persons aged 45 to 84 years who were free of clinical CVD at baseline (2000–2002). Participants with complete fasting lipid profiles (n=6704) were evaluated for CVD risk and self-reported use of lipid-lowering therapy. CAC was assessed by CT. Drug treatment thresholds and goals were defined according to ATP III. Models were constructed to adjust for age, clinic site, risk factors, socioeconomic characteristics, and healthcare access variables with the use of Poisson regression. Overall, 29.3% (1964/6704) had dyslipidemia, among whom lipid-lowering drug therapy was reported by 54.0% (1060/1964). Control to ATP III goal was observed in 75.2% (797/1060) of participants with treated dyslipidemia and 40.6% (797/1964) of participants with dyslipidemia. Men were more likely than women to qualify for drug therapy and less likely to be treated and controlled. Relative to non-Hispanic whites, Chinese Americans were less likely to qualify for drug treatment, but no differences in treatment and control rates were observed. Black and Hispanic Americans had prevalence of dyslipidemia that was comparable to that of non-Hispanic whites but were less likely to be treated and controlled. Ethnic disparities were attenuated substantially by adjustment for healthcare access variables; however, the gender disparities persisted despite adjustment for risk factors, socioeconomic characteristics, and healthcare access variables. Control of dyslipidemia was achieved less commonly in the CVD high- and intermediate-risk groups than in the low-risk group. Among high-risk individuals, 19.7% of those who did not qualify for lipid-lowering drug treatment had CAC >400. The proportion of drug treatment–qualifying persons who were not treated differed by presence and severity of CAC, with 48.0%, 46.8%, and 39.6% of eligible persons with no CAC, with CAC >0 and <400, and with CAC >400 not receiving treatment, respectively (P for difference=0.04). Conclusions— Dyslipidemia is common among persons without CVD. The quality of care for dyslipidemia is suboptimal in general and variable by CVD risk group, ethnicity, and gender. The utility of incorporating CAC screening into the risk stratification and treatment process should be investigated in light of the substantial proportions of persons with CAC who are currently classified as not requiring treatment. Research and quality improvement programs are needed to optimize management of dyslipidemia.

Increasing body mass index and obesity in the incident ESRD population

An increase in obesity prevalence among patients who initiate dialysis may influence the growth of the total ESRD population as a result of improved survival and decreased likelihood for transplantation. Temporal trends in mean body mass index (BMI) and obesity prevalence were examined among incident patients with ESRD by year of dialysis initiation between 1995 and 2002, and these trends were compared with those in the US population during this same period. Among incident dialysis patients, BMI was calculated with the height and estimated dry weight collected from the Centers for Medicare and Medicaid Services End-Stage Renal Disease Medical Evidence Form. In the US population, self-reported height and weight were used. Prevalence of total obesity and obesity stage > or =2 were defined as a BMI > or =30 and > or =35 kg/m(2), respectively. Among incident patients with ESRD, mean BMI increased from 25.7 to 27.5 kg/m(2), and total obesity and obesity stage > or =2 increased by 33 and 63%, respectively, among incident patients with ESRD (P < 0.0001 for obesity trends). BMI slope was approximately two-fold higher in the incident ESRD population compared with the US population for all age groups. However, temporal increases in obesity prevalence were similar between the two populations. As a result of the survival advantage associated with obesity and decreased likelihood for transplantation, these trends most likely will influence the total number of patients who receive dialysis in the next decade.

Association between Chronic Kidney Disease and Coronary Artery Calcification: The Dallas Heart Study

The hypothesis that chronic kidney disease (CKD) is associated with increased coronary artery calcification (CAC) was tested using data from the Dallas Heart Study, a representative sample of Dallas County residents aged 30 to 65 yr. CKD was defined as presence of microalbuminuria and GFR > or =60 ml/min per 1.73 m(2) (stage 1 to 2), or GFR <60 ml/min per 1.73 m(2) (stage 3 to 5), excluding end-stage kidney disease. Logistic regression was used to examine the association between stages of CKD and CAC scores >10, >100, and >400 versus scores < or =10 compared with no CKD while adjusting for covariates. Analyses were repeated after stratifying by presence of diabetes. The mean age was 43.9 yr, and hypertension and diabetes were noted in 31.0 and 9.8%, respectively. No association was noted between stage 1 to 2 CKD and increased CAC scores. Compared with no CKD, stage 3 to 5 CKD was associated with CAC scores >100 (odds ratio, 2.85; 95% confidence interval, 0.92 to 8.80) and >400 (odds ratio, 8.35; 95% confidence interval, 1.94 to 35.95) in the total population after adjustment for covariates, but these associations were substantially reduced after exclusion of participants with diabetes. Participants with diabetes and stage 3 to 5 CKD had a ninefold increased odds of CAC scores >10 versus scores < or =10 compared with participants with diabetes and without CKD, whereas no association was noted between stage 3 to 5 CKD and CAC scores >10 in the nondiabetic population. In conclusion, stage 3 to 5 CKD is associated with increased CAC scores, but this association may be substantially stronger among adults with diabetes. These findings need to be confirmed in study populations that include adults >65 yr of age and a larger number of CKD cases.

Adverse renal consequences of obesity

Emerging evidence indicates that obesity, even in the absence of diabetes, contributes significantly to the development and progression of chronic kidney disease (CKD). Glomerular hyperfiltration/hypertrophy in response to the increased metabolic needs of obesity are postulated to lead to the development of glomerulosclerosis (GS) in a manner analogous to that in reduced renal mass states. Nevertheless, the individual risk for developing GS with obesity is very low. It is proposed that glomerular hyperfiltration/hypertrophy are per se not pathogenic in the absence of an enhanced glomerular blood pressure (BP) transmission, and the modest preglomerular vasodilation that is likely present in the large majority of obese individuals is not sufficient to result in such increased BP transmission. However, in the small subset of obese individuals who are also born with a substantially reduced nephron number, there is a greater risk of enhanced glomerular BP transmission due to the substantially greater preglomerular vasodilation. Of perhaps greater clinical importance, similar additive deleterious effects of obesity on BP transmission would be expected in individuals with reduced renal mass, either congenital or acquired, or with concurrent renal disease, leading to accelerated progression. Of note, a low birth weight may be a risk factor for not only reduced nephron numbers at birth, but also for obesity and hypertension, resulting in a clustering of risk factors for progressive GS. Therefore, even though the individual risk for developing obesity GS is low, the cumulative impact of obesity on the public health burden of CKD is likely to be large because of its huge prevalence.

Metabolic Syndrome and Self-Reported History of Kidney Stones: The National Health and Nutrition Examination Survey (NHANES III) 1988-1994

BACKGROUND Metabolic syndrome affects approximately 25% of the American population. Components of metabolic syndrome, such as obesity, hypertension, and diabetes, were associated with kidney stone disease, but no published large-scale study examined the association between metabolic syndrome and history of kidney stones. STUDY DESIGN Cross-sectional analysis. The American Heart Association and National Heart, Lung, and Blood Institute statement on metabolic syndrome was used to define metabolic syndrome. SETTING & PARTICIPANTS A national probability sample of the US population National Health and Nutrition Examination Survey aged 20 years and older. PREDICTOR Metabolic syndrome as defined by the American Heart Association and National Heart, Lung, and Blood Institute. OUTCOMES & MEASUREMENTS Self-reported history of kidney stones. RESULTS Of all adults older than 20 years, 4.7% reported a history of kidney stones. The prevalence of self-reported history of kidney stones increased with the number of metabolic syndrome traits from 3% with 0 traits to 7.5% with 3 traits to 9.8% with 5 traits. After adjustment for age and other covariates, the presence of 2 or more traits significantly increased the odds of self-reported kidney stone disease. The presence of 4 or more traits was associated with an approximate 2-fold increase in odds of self-reported kidney stone disease. LIMITATIONS Cross-sectional design, absence of dietary data. CONCLUSION Metabolic syndrome traits are associated with a self-reported history of kidney stones. This association should be verified in prospective studies.

Urine albumin excretion and subclinical cardiovascular disease : The multi-ethnic study of atherosclerosis

We examined the association between urine albumin excretion (UAE) and common and internal carotid artery intima-media thickness (IMT), end-diastolic left ventricular (LV) mass, and coronary artery calcification (CAC) scores using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of 6814 adults aged 45 to 85 years without clinical cardiovascular disease (CVD). The mean age of the MESA participants was 62.7 years, 47% were male, and 15% had diabetes mellitus (DM). Sex-specific spot urine albumin/creatinine ratios were used to define 4 UAE categories: normal, high normal, microalbuminuria, and macroalbuminuria. CAC scores were log-transformed after adding 1 to all scores. Mean values of subclinical CVD measures were computed by level of UAE after adjustment for blood pressure, DM, and other covariates. After adjustment for all covariates, geometric mean CAC scores were higher among participants with high normal UAE (8.8; P=0.07), microalbuminuria (9.9; P=0.002), and macroalbuminuria (13.1; P=0.02) compared with normal UAE (7.4), but only microalbuminuria reached statistical significance. Mean LV mass (g/m2.7) was significantly higher in participants with high normal UAE (37.0; P=0.001), microalbuminuria (38.3; P≤0.0001), and macroalbuminuria (42.3; P≤0.0001) compared with normal UAE (36.0) after adjustment for all covariates. No significant difference in mean carotid IMT was found after adjustment for all covariates. Similar results were noted in MESA participants with and without DM. In conclusion, higher UAE, including levels below microalbuminuria, may reflect the presence of subclinical CVD among adults without established CVD.

Obesity and Kidney Disease: Potential Mechanisms

Assessment of adiposity should include measurements of both body mass index and waist circumference. The prevalence of obesity, based on a body mass index of 30 kg/m(2) or greater, has increased substantially over the past 2 decades in Western societies. Obesity remains the number one preventable risk factor for chronic kidney disease because obesity largely mediates diabetes and hypertension, the 2 most common etiologies for end-stage kidney disease. However, obesity itself likely has independent effects on renal hemodynamics and individuals with a low number of nephrons are likely to be the most susceptible to these changes. Multiple mechanisms have been postulated whereby obesity directly impacts kidney disease including hyperfiltration, increased glomerular capillary wall tension, and podocyte stress. Weight loss reduces glomerular filtration rate and effective renal plasma flow along with proteinuria, but these changes are most notable after bariatric surgery in adults with morbid obesity. Aside from adiposity itself, the high caloric intake that leads to obesity also may heighten chronic kidney disease risk via the circuitous loop between Sirt1 and adiponectin and podocyte effacement. Sirt1 is a nicotinamide adenine dinucleotide+dependent deacteylase that is up-regulated in the setting of caloric restriction. Sirt1 expression modulates adiponectin levels that in turn appear to influence podocyte effacement. Clinical trials are needed to assess the benefits and risks of intentional weight loss on kidney disease measures and progression.

Genetic association for renal traits among participants of African Ancestry reveals new loci for renal function

Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m2), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10−7) and FNDC1 (p-value = 3.0×10−7) for UACR, and KCNQ1 with eGFR (p = 3.6×10−6). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish.

Association of Waist Circumference and Body Mass Index With All-Cause Mortality in CKD: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study

BACKGROUND Obesity management requires understanding the mortality risks associated with different adiposity measures. STUDY DESIGN Prospective cohort. SETTING & PARTICIPANTS 5,805 adults with body mass index (BMI) ≥18.5 kg/m(2) and stages 1-4 chronic kidney disease, defined as a spot urine albumin-creatinine ratio ≥30 mg/g and/or estimated glomerular filtration rate <60 mL/min/1.73 m(2), enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. PREDICTOR BMI categorized as 18.5-24.9, 25.0-29.9, 30.0-34.9, 35.0-39.9, and ≥40 kg/m(2) and waist circumference categorized as <80, 80-87.9, 88-97.9, 98-107.9, and ≥108 cm in women and <94, 94-101.9, 102-111.9, 112-121.9, and ≥122 cm in men. OUTCOMES All-cause mortality. MEASUREMENTS BMI and waist circumference were measured using a standardized protocol during the home visit. RESULTS 686 (11.8%) deaths occurred during a median follow-up of 4 years. Compared with the referent BMI category of 25-29.9 kg/m(2), HRs for mortality were 1.27 (95% CI, 0.96-1.69) for BMI <25 kg/m(2) and 0.84 (95% CI, 0.62-1.13), 0.81 (95% CI, 0.52-1.26), and 0.95 (95% CI, 0.54-1.65) for BMI categories 30-34.9, 35-39.9, and ≥40 kg/m(2) after adjustment for covariates including waist circumference, respectively. In contrast, after adjustment for covariates including BMI, higher mortality rates were noted for all waist circumference categories compared with the referent (<80 cm in women and <94 cm in men), with HRs of 1.04 (95% CI, 0.77-1.41) for waist circumference of 80-87.9 cm in women and 94-101.9 cm in men, 1.29 (95% CI, 0.92-1.81) for waist circumference of 88-97.9 cm in women and 102-111.9 cm in men, 1.72 (95% CI, 1.12-2.62) for waist circumference of 98-107.9 cm in women and 112-121.9 cm in men, and 2.09 (95% CI, 1.26-3.46) for waist circumference ≥108 cm in women and ≥122 cm in men. LIMITATIONS BMI and waist circumference measured at baseline only. CONCLUSIONS Waist circumference should be considered in conjunction with BMI when assessing mortality risk associated with obesity in adults with chronic kidney disease.