A multicenter cohort study of primary hypertension in Korea: study design and interim analysis of the Korean registry of target organ damage in hypertension (KorHR)
Received: 6 February 2017
Accepted: 12 June 2017
Published: 2 August 2017
Abstract
Background
The Korean Registry of Target Organ Damage in Hypertension aims to evaluate the clinical characteristics and prevalence of subclinical target organ damage in Korean hypertensive patients.
Method
This is a prospective, observational, multicenter cohort study in which 23 university hospitals participated. Since May 2013, we have enrolled 1,318 consecutive hypertensive patients without known cardiovascular disease who met the following inclusion criteria: 1) age older than 30 years and 2) the first visit to the participating hospitals was within the last 5 years.
Results
The mean age was 52 ± 12 years; 62.1% were male, and 41.3% were incident hypertensives. Patients with diabetes mellitus accounted for 7.8% of the population and 43.8% had hyperlipidemia or were on statins at baseline. The mean office blood pressures were 152 ± 20/96 ± 14 mmHg for incident hypertensive patients and 129 ± 13/78 ± 10 mmHg for patients on treatment. Patients with electrocardiographic and echocardiographic left ventricular hypertrophy accounted for 18.9 and 25.6%, respectively. The mean brachial-ankle pulse wave velocity (PWV) was 1564 ± 293 m/s and 19.5% had PWV values of more than 1750 cm/s. Patients with microalbuminuria and chronic kidney disease accounted for 21 and 4%, respectively. The first prescribed class of antihypertensive medications was angiotensin converting enzyme inhibitors in 2.9%, angiotensin receptor blockers (ARBs) in 57.5%, diuretics in 7.6%, calcium channel blockers (CCBs) in 61.0%, beta blockers in 17.3%, and fixed dose combination pill in 27.8%.
Conclusion
Our interim analysis shows that subclinical target organ damage in hypertension is considerably present for incident or treated hypertensive patients. CCBs and ARBs were the most commonly prescribed classes of antihypertensive medications and fixed dose combination pills were actively used in Korea.
Trial registration
NCT01861080. Registered 16 May 2013
Keywords
Background
Hypertension is an important worldwide public-health challenge because of its high frequency and concomitant risk of cardiovascular and kidney disease [1]. Substantial evidence has established that lowering high blood pressure (BP) is an effective way to prevent cardiovascular and renal diseases [2]. Along with controlling BP, identification and treatment of other cardiovascular risk factors, such as hyperlipidemia, smoking, and diabetes mellitus, is crucial in the management of hypertension.
Another important factors in the risk stratification and management of hypertensive patients are the existence of subclinical target organ damages (SODs) such as left ventricular hypertrophy (LVH), carotid wall thickening, increased pulsed wave velocity (PWV), chronic kidney disease (CKD) with a reduced estimated glomerular filtration rate (eGFR), and microalbuminuria (MAU) [3]. In the European hypertension guidelines, active search for SODs is highly recommended because it allows a better stratification of the cardiovascular risk and helps physicians select the most appropriate antihypertensive medicines [3].
Despite the emphasis of guidelines on active investigation for SOD, large-population based data are limited in terms of the prevalence of SODs in Korean hypertensives. Therefore, we aimed to determine the prevalence of SODs and distinct characteristics in Korean hypertensives by constructing a nationwide hypertension registry. Hereafter, we report the study design and interim analysis of the Korean Registry of Target Organ Damage in Hypertension (KorHR).
Methods
Study design
The KorHR is a prospective, observational, multicenter cohort study in which 24 university hospitals in the Republic of Korea participated. From May 2013, patients were consecutively enrolled if they 1) were older than 30 years old, 2) had primary hypertension, and 3) consented to registry enrollment. Study patients were classified into one of two tracks. One is a group of patients who were diagnosed with primary hypertension at enrollment and had never taken an antihypertensive medication (incident group). Patients were also considered as the incident group if they had been diagnosed with primary hypertension before enrollment and had not taken antihypertensive medications for more than 2 weeks from the time of enrollment. The second is a group of patients who had taken antihypertensive treatment before the study enrollment and first visited research institutions within the past 5 years (on-treatment group).
We excluded patients with obvious cardiovascular disease at baseline, such as cerebrovascular disease, coronary artery disease, heart failure, peripheral artery disease, and CKD with an eGFR of less than 30 mL/min/1.73 m2.
At the baseline visit, the demographic and anthropometric characteristics of eligible patients were recorded and the medical history, such as diabetes mellitus (DM), hyperlipidemia, regular exercise, and smoking were also reported. DM was defined as fasting plasma glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5% or if patient were taking anti-diabetic medications. Hyperlipidemia was defined as total cholesterol ≥ 240 mg/dL or low density lipoprotein ≥ 160 mg/dL or triglyceride ≥ 200 mg/dL or if patients were taking statins. Regular exercise was defined if patients do exercise (aerobic or anaerobic) for more than 30 min at a time and at least three times a week. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured two or three times in both arms at intervals of 3 min in accordance with the official recommendations for BP measurements [4]. The mean values of each measurement was recorded as the office BPs. Ambulatory BP monitoring was also used to rule out patients with white coat hypertension and evaluate the BP status. Laboratory tests were performed, including simple urinalysis, complete blood count, serum chemistry, serum lipid, serum uric acid, plasma renin activity, and aldosterone. The SODs of hypertension such as LVH, MAU, CKD, and increased PWV, were thoroughly scrutinized.
Finally, we investigated each class of antihypertensive medication that was prescribed first and analyzed a trend of antihypertensive treatment with medicines. We aimed to evaluate the cardiovascular outcomes for up to 5 years, including all cause death, cardiovascular death, ischemic or hemorrhagic stroke, myocardial infarction, coronary revascularization, and heart failure, although we do not report on the cardiovascular outcomes in this interim analysis.
Definitions of the primary outcome
The primary outcome was the presence of SODs of hypertension, such as LVH, increased PWV, CKD with an eGFR of 30–60 mL/min/1.73 m2, and MAU. Electrocardiographic LVH was defined by the modified Sokolow-Lyon index (largest S-wave + largest R-wave > 3.5 mV) and the assessment of echocardiographic LVH was based on the criteria proposed by the European hypertension guidelines [left ventricular mass index: men >115 g/m2 and women >95 g/m2 (BSA)] [3]. Left ventricular mass was calculated according to linear method using the following equation [5].
Left ventricular mass = 0.8 * 1.04 * [(thickness of interventricular septum at diastole + left ventricular internal diameter at diastole + posterior wall thickness at diastole)3 – (left ventricular internal dimension at diastole)3] + 0.6 g.
A threshold of >1,750 cm/s for the baPWV was determined for the presence of SOD, which was the cut-off value of baPWV for predicting cardiovascular disease in previous studies [9, 10].
Statistical analysis
Continuous variables were expressed as the mean ± standard deviation (SD) and were compared using the t test or Wilcoxon’s rank-sum test. Categorical data were expressed as frequencies and percentages, and they were compared using the χ 2 test or Fisher’s exact test. Continuous variables were compared using the student’s t test or by the nonparametric Mann-Whitney U test. For all tests, a probability value of p <0.05 was considered significant. All statistical analyses were performed using statistical software SPSS (Chicago, Illinois) version 19.0.
Results
Baseline characteristics
Overall (N = 1,318) | Incident (N = 611) | On treatment (N = 707) | |
|---|---|---|---|
Age, years ± SD | 52 ± 12 | 47 ± 11 | 56 ± 11 |
Males (%) | 818 (62.1) | 415 (67.9) | 403 (57.0) |
BMIa (kg/m2) ± SDb | 25.9 ± 3.5 | 26.2 ± 3.6 | 25.8 ± 3.4 |
Obesityc (%) | 56.8 | 61.2 | 52.8 |
Waist (cm) ± SD | 88 ± 9 | 89.7 ± 8.8 | 87 ± 9 |
Office SBP (mmHg) ± SD | 140 ± 20 | 152 ± 20 | 129 ± 13 |
Office DBP (mmHg) ± SD | 86 ± 15 | 96 ± 14 | 78 ± 10 |
Office HR (beats per minute) ± SD | 75 ± 18 | 77 ± 12 | 72 ± 11 |
Hypertension awareness (months) | 48 ± 65 | 22 ± 40 | 71 ± 74 |
Diabetes mellitus (%) | 7.8 | 3.9 | 11.0 |
Hyperlipidemia (%) | 43.8 | 35.1 | 51.0 |
Regular exercise (%) | 32.3 | 28.8 | 39.8 |
Smoking (%) | |||
Never | 54.8 | 51.5 | 57.4 |
Past | 19.4 | 15.1 | 22.8 |
Current | 20.2 | 25.6 | 15.8 |
Laboratory Data
Overall (N = 1,318) | Incident (N = 611) | On treatment (N = 707) | |
|---|---|---|---|
Hemoglobin (g/dL) | 14.6 ± 3.5 | 14.9 ± 1.6 | 14.4 ± 4.6 |
Hematocrit (%) | 43.0 ± 4.5 | 44.0 ± 4.8 | 42.1 ± 3.9 |
Glucose (mg/dL) | 108 ± 25 | 106 ± 24 | 109 ± 26 |
Impaired fasting glucose (%) | 59.8 | 56.0 | 63.0 |
Total cholesterol (mg/dL) | 188 ± 36 | 200 ± 36 | 177 ± 32 |
Triglyceride (mg/dL) | 151 ± 109 | 166 ± 128 | 139 ± 87 |
HDL (mg/dL) | 52 ± 14 | 51 ± 15 | 52 ± 13 |
LDL (mg/dL) | 114 ± 33 | 127 ± 32 | 104 ± 31 |
Uric acid (mg/dL) | 5.5 ± 2.4 | 5.8 ± 3.2 | 5.3 ± 1.4 |
Estimated GFR (mL/min/1.73 m2) | 89 ± 20 | 93 ± 26 | 87 ± 21 |
Urine albumin creatinine ratio (mg/g), median (1/4 quartile, 3/4 quartile) | 10.3 (4.9, 24.8) | 10.5 (5.0, 23.7) | 10.1 (4.8, 25.5) |
Renin (ng/ml/h) | 3.35 ± 6.75 | 3.12 ± 6.76 | 4.16 ± 6.71 |
Aldosterone (pg/mL) | 9.8 ± 7.5 | 9.6 ± 6.5 | 10.42 ± 10.05 |
PWVa | 1558 ± 285 | 1569 ± 289 | 1543 ± 278 |
Central SBP | 133 ± 20 | 136 ± 19 | 130 ± 21 |
Central DBP | 88 ± 13 | 92 ± 12 | 83 ± 12 |
Augmentation index | 38 ± 27 | 33 ± 24 | 47 ± 28 |
Values of Twenty-four hour ambulatory blood pressure monitoring. 24 h, 24 h average; SBP, systolic blood pressure; DBP, diastolic blood pressure; Day, awake time average; Night, sleep time average
Prevalence of subclinical target organ damage. SOD, subclinical organ damage; Echo LVH, echocardiographic left ventricular hypertrophy; ECG LVH, electrocardiographic left ventricular hypertrophy; MAU, microalbuminuria; CKD, chronic kidney disease; PWV, pulse wave velocity
Echocardiographic left ventricular hypertrophy
Overall (N = 524) | Incident (N = 281) | On treatment (N = 243) | p value | |
|---|---|---|---|---|
LVH | 25.6 | 22.8 | 28.8 | 0.132 |
Concentric LVH (%) | 11.5 | 12.8 | 9.9 | 0.336 |
Eccentric LVH (%) | 14.1 | 10.0 | 18.9 | 0.004 |
Concentric remodeling (%) | 12.2 | 12.1 | 12.3 | 0.932 |
Normal (%) | 62.2 | 65.1 | 58.8 | 0.149 |
The class of antihypertensive medicines prescribed at baseline was investigated. The most frequently prescribed class was calcium channel blockers (CCBs) (61%), which was followed by angiotensin receptor blockers (ARBs) (57.5%), beta blockers (17.6%), diuretics (7.6%), and angiotensin converting enzyme (ACE) inhibitors (2.9%). Among them, 27.8% were prescribed with a fixed dose combination pill; most of these combination pills were an ARB plus CCB (83.6%).
Discussion
This study shows the integrated prevalence of SODs for primary hypertension in hypertensive patients in Korea. SODs in primary hypertension were quite prevalent: 18.9% for ECG LVH, 25.6% for echo LVH, 19% for MAU, and 19.5% for increased PWV.
With respect to the LVH, eccentric LVH (14.1%) was slightly more frequent than concentric LVH (11.5%) in all subjects. Notably, although concentric LVH seemed to be more common in the incident group than in the on-treatment group, albeit not statistically significant, eccentric LVH was significantly more frequent in the on-treatment group than in the incident group. This finding is consistent with previous studies, including a recent systemic review on echocardiographic LVH [11, 12]. Mancia et al. reported that eccentric LVH was more frequent than concentric LVH and the change in the left ventricular geometry due to high BP was retained regardless of whether the BP was normal or elevated and whether treatment did or did not achieve BP control [11]. As mentioned above, approximately 75% of patients in the on-treatment group in this study achieved target BP. As they proposed, the persistence of cardiac structure abnormalities such as LVH may not completely regress even after achieving target BPs. Additionally, the structural geometry may change with treatment, i.e., from concentric LVH to eccentric LVH with alteration of the RAS system. Concentric LVH was associated with a worse prognosis than the eccentric LVH [13]. However, eccentric LVH was also a significant predictor of the development of low LVEF. [14] Therefore, this result showed that even incident hypertensive patients are exposed to a risk of cardiovascular diseases in addition to patients on hypertensive treatment regardless of whether they achieved target BP. In contrast to echocardiographic LVH, electrocardiographic LVH was more prevalent in the incident group than in the on-treatment group. This finding can be explained that electrocardiographic change due to LVH and BP control might occur more easily than an echocardiographic left ventricular mass change.
MAU is known to be the integrated marker of SODs in primary hypertension [15]. MAU is associated with metabolic derangements and an increased cardiovascular risk in hypertension patients [16, 17]. The previously reported prevalence of MAU varies from 4.7 to 40% according to study populations [18–23]. Among them, the I-DEMAND (Italy Developing Education and awareness on Microalbuminuria in hypertensive Disease) study, which enrolled patients with similar characteristics as this study, showed that the overall prevalence of MAU was 27% in 3,534 hypertensive patients [19]. Two previous Korean studies showed that the prevalence of MAU were 5.4 and 10.1%, which included patients who visited primary clinics or participated in the health examination program [22, 23]. Several factors are known for affecting the prevalence of MAU. MAU is more frequent in patients with high stages of hypertension [24]. In addition to the severity of hypertension, age, sex, obesity, and concomitant risk factors could influence the presence of MAU, although other studies report conflicting results [20, 25–27]. The difference between the present study and other Korean studies is mainly due to the characteristics of patients who visited different clinical settings, such as primary clinics and referral hypertension specialized clinics. The result suggests that MAU is significantly prevalent in Korean hypertensive patients and active investigation for MAU is encouraged for all hypertensive patients, as recommended by the guidelines. Although the prevalence of asymptomatic CKD was rare in incident hypertensives (2.4%), it rose to a considerable level (5.3%) in patients who have been treated with antihypertensive medicines for up to 5 years.
The carotid-femoral PWV (cfPWV) has been acknowledged as the standard of arterial stiffness [28]. However, the baPWV, which is much easier to measure, is more available in South Korea. Previous reports have shown that baPWV was correlated well with cfPWV and predicted worse outcomes in hypertensive patients [29, 30]. These studies suggest that the baPWV cut-off value was approximately 1750 cm/s, which was associated with increased cardiovascular events and mortality [9, 10, 31, 32]. In this study, an overall prevalence of baPWV of more than 1750 cm/s was 11.9%. The prevalence of increased baPWV was significantly higher in the incident group than in the on-treatment group (16.0% vs. 8.3%, p < 0.001), which could probably be affected by the high BP status of the incident group.
This study has limitations. First, we enrolled patients who visited hypertension specialized clinics in university hospitals. Because these patients could not be extrapolated to general population with hypertension, the prevalence of SODs could be exaggerated. Second, the performance rate of ECG, MAU, PWV, and 2D echocardiography was 82, 71, 61 and, 40%. Therefore, the findings of 2D echocardiography could be skewed. However, the prevalence of each SOD was quite comparable to previous studies.
Finally, our analysis of antihypertensive medicines demonstrated that CCBs and ARBs are the most commonly prescribed antihypertensive medicines. Notably, ACE inhibitors were rarely prescribed, which is probably due to the high incidence of ACE inhibitor-induced cough in Asians [33]. Furthermore, fixed dose combination pills, which are expected to improve drug compliance, are actively used in South Korea. [34] In South Korea, there is no commercially available fixed dose combination pill that incorporates both an ACE inhibitor and CCB, which could explain the high rate of ARB uses.
Conclusions
Interim analysis of the KorHR study showed that SODs of hypertension were prevalent in both incident and on-treatment hypertensive patients. In terms of medicines, CCBs and ARBs were the most commonly prescribed classes of antihypertensive medications and fixed dose combination pills are actively used in South Korea.
Declarations
Acknowledgement
We thank Sang-Hyun Ihm, Eung-Ju Kim, Eun-Joo Cho, Sang-Ho Jo, Seong Hun Choi, Sung Hea Kim who enrolled study patients. In particular, we thank the Korean Society of Hypertension which support to build our registry.
Funding
This research was supported by the funding of Korean Society of Hypertension(2011).
Availability of data and materials
Not applicable
Authors’ contribution
SWC and KHR recruited and analyzed patients’ data and wrote the manuscript. JSO did data management. SWH, BSY, MSS, and SHP recruited enrolled study patients and contributed data analysis. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Ethics approval and consent to participate
The study was approved by the local ethics committee or institutional review board of each participating center. All patients provided written informed consent before enrollment.
Consent for publication
Not applicable
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Authors’ Affiliations
References
- Whelton PK. Epidemiology of hypertension. Lancet. 1994;344:101–6.View ArticlePubMedGoogle Scholar
- Czernichow S, Zanchetti A, Turnbull F, Barzi F, Ninomiya T, Kengne AP, et al. The effects of blood pressure reduction and of different blood pressure-lowering regimens on major cardiovascular events according to baseline blood pressure: meta-analysis of randomized trials. J Hypertens. 2011;29:4–16.View ArticlePubMedGoogle Scholar
- Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the European society of cardiology (ESC). Eur Heart J. 2013;34:2159–219.View ArticlePubMedGoogle Scholar
- Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the subcommittee of professional and public education of the American heart association council on high blood pressure research. Hypertension. 2005;45:142–61.View ArticlePubMedGoogle Scholar
- Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American society of Echocardiography’s guidelines and standards committee and the chamber quantification writing group, developed in conjunction with the European society of cardiology. J Am Soc Echocardiogr. 2005;18(12):1440–63.View ArticlePubMedGoogle Scholar
- Redon J. Urinary albumin excretion: lowering the threshold of risk in hypertension. Hypertension. 2005;46:19–20.View ArticlePubMedGoogle Scholar
- National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–266.Google Scholar
- Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145:247–54.View ArticlePubMedGoogle Scholar
- Kawai T, Ohishi M, Onishi M, Ito N, Takeya Y, Maekawa Y, et al. Cut-off value of brachial-ankle pulse wave velocity to predict cardiovascular disease in hypertensive patients: a cohort study. J Atheroscler Thromb. 2013;20:391–400.View ArticlePubMedGoogle Scholar
- Munakata M, Konno S, Miura Y, Yoshinaga K. Prognostic significance of the brachial-ankle pulse wave velocity in patients with essential hypertension: final results of the J-TOPP study. Hypertens Res. 2012;35:839–42.View ArticlePubMedGoogle Scholar
- Mancia G, Carugo S, Grassi G, Lanzarotti A, Schiavina R, Cesana G, et al. Prevalence of left ventricular hypertrophy in hypertensive patients without and with blood pressure control: data from the PAMELA population. Pressioni Arteriose Monitorate E Loro Associazioni. Hypertension. 2002;39:744–9.View ArticlePubMedGoogle Scholar
- Cuspidi C, Sala C, Negri F, Mancia G, Morganti A. Prevalence of left-ventricular hypertrophy in hypertension: an updated review of echocardiographic studies. J Hum Hypertens. 2012;26:343–9.View ArticlePubMedGoogle Scholar
- Muiesan ML, Salvetti M, Monteduro C, Bonzi B, Paini A, Viola S, et al. Left ventricular concentric geometry during treatment adversely affects cardiovascular prognosis in hypertensive patients. Hypertension. 2004;43:731–8.View ArticlePubMedGoogle Scholar
- Drazner MH, Rame JE, Marino EK, Gottdiener JS, Kitzman DW, Gardin JM, et al. Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the cardiovascular health study. J Am Coll Cardiol. 2004;43:2207–15.View ArticlePubMedGoogle Scholar
- Leoncini G, Sacchi G, Ravera M, Viazzi F, Ratto E, Vettoretti S, et al. Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension. J Hum Hypertens. 2002;16:399–404.View ArticlePubMedGoogle Scholar
- Halimi JM, Forhan A, Balkau B, Novak M, Wilpart E, Tichet J, et al. Is microalbuminuria an integrated risk marker for cardiovascular disease and insulin resistance in both men and women? J Cardiovasc Risk. 2001;8:139–46.View ArticlePubMedGoogle Scholar
- de la Sierra A, Bragulat E, Sierra C, Gomez-Angelats E, Antonio MT, Aguilera MT, et al. Microalbuminuria in essential hypertension: clinical and biochemical profile. Br J Biomed Sci. 2000;57:287–91.PubMedGoogle Scholar
- Calvino J, Calvo C, Romero R, Gude F, Sanchez-Guisande D. Atherosclerosis profile and microalbuminuria in essential hypertension. Am J Kidney Dis. 1999;34:996–1001.View ArticlePubMedGoogle Scholar
- Leoncini G, Viazzi F, Rosei EA, Ambrosioni E, Costa FV, Leonetti G, et al. Chronic kidney disease in hypertension under specialist care: the I-DEMAND study. J Hypertens. 2010;28:156–62.View ArticlePubMedGoogle Scholar
- Jensen JS, Feldt-Rasmussen B, Borch-Johnsen K, Clausen P, Appleyard M, Jensen G. Microalbuminuria and its relation to cardiovascular disease and risk factors. A population-based study of 1254 hypertensive individuals. J Hum Hypertens. 1997;11:727–32.View ArticlePubMedGoogle Scholar
- Cerasola G, Cottone S, Mule G, Nardi E, Mangano MT, Andronico G, et al. Microalbuminuria, renal dysfunction and cardiovascular complication in essential hypertension. J Hypertens. 1996;14:915–20.View ArticlePubMedGoogle Scholar
- Choi HS, Sung KC, Lee KB. The prevalence and risk factors of microalbuminuria in normoglycemic, normotensive adults. Clin Nephrol. 2006;65:256–61.View ArticlePubMedGoogle Scholar
- Kim YS, Kim HS, Oh HY, Lee MK, Kim CH, Kim YS, et al. Prevalence of microalbuminuria and associated risk factors among adult Korean hypertensive patients in a primary care setting. Hypertens Res. 2013;36:807–23.View ArticlePubMedGoogle Scholar
- Jones CA, Francis ME, Eberhardt MS, Chavers B, Coresh J, Engelgau M, et al. Microalbuminuria in the US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2002;39:445–59.View ArticlePubMedGoogle Scholar
- Cirillo M, Senigalliesi L, Laurenzi M, Alfieri R, Stamler J, Stamler R, et al. Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass index, plasma cholesterol levels, and smoking: the gubbio population study. Arch Intern Med. 1998;158:1933–9.View ArticlePubMedGoogle Scholar
- Pontremoli R, Sofia A, Ravera M, Nicolella C, Viazzi F, Tirotta A, et al. Prevalence and clinical correlates of microalbuminuria in essential hypertension: the MAGIC study. Microalbuminuria: a Genoa investigation on complications. Hypertension. 1997;30:1135–43.View ArticlePubMedGoogle Scholar
- Palatini P, Graniero GR, Mormino P, Mattarei M, Sanzuol F, Cignacco GB, et al. Prevalence and clinical correlates of microalbuminuria in stage I hypertension. Results from the hypertension and ambulatory recording Venetia study (HARVEST study). Am J Hypertens. 1996;9:334–41.View ArticlePubMedGoogle Scholar
- Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588–605.View ArticlePubMedGoogle Scholar
- Ninomiya T, Kojima I, Doi Y, Fukuhara M, Hirakawa Y, Hata J, et al. Brachial-ankle pulse wave velocity predicts the development of cardiovascular disease in a general Japanese population: the hisayama study. J Hypertens. 2013;31:477–83. discussion 483.View ArticlePubMedGoogle Scholar
- Tanaka H, Munakata M, Kawano Y, Ohishi M, Shoji T, Sugawara J, et al. Comparison between carotid-femoral and brachial-ankle pulse wave velocity as measures of arterial stiffness. J Hypertens. 2009;27:2022–7.View ArticlePubMedGoogle Scholar
- Hae Guen S, Eung Ju K, Hong Seog S, Seong Hwan K, Chang Gyu P, Seong Woo H, et al. Relative contributions of different cardiovascular risk factors to significant arterial stiffness. Int J Cardiol. 2010;139:263–8.View ArticleGoogle Scholar
- Sehestedt T, Jeppesen J, Hansen TW, Rasmussen S, Wachtell K, Ibsen H, et al. Thresholds for pulse wave velocity, urine albumin creatinine ratio and left ventricular mass index using SCORE, Framingham and ESH/ESC risk charts. J Hypertens. 2012;30:1928–36.View ArticlePubMedGoogle Scholar
- Watson RE, Karnchanasorn R, Gossain VV. Hypertension in Asian/Pacific Island Americans. J Clin Hypertens (Greenwich). 2009;11:148–52.View ArticleGoogle Scholar
- Stanton T, Reid JL. Fixed dose combination therapy in the treatment of hypertension. J Hum Hypertens. 2002;16:75–8.View ArticlePubMedGoogle Scholar
