Peak flow as a predictor of cause-specific mortality in China: results from a 15-year prospective study of ∼170 000 men

Abstract Background Forced expiratory volume in one second (FEV1) is inversely associated with mortality in Western populations, but few studies have assessed the associations of peak expiratory flow (PEF) with subsequent cause-specific mortality, or have used populations in developing countries, including China, for such assessments. Methods A prospective cohort study followed ∼170 000 Chinese men ranging in age from 40–69 years at baseline (1990–1991) for 15 years. In the study, height-adjusted PEF (h-PEF), which was uncorrelated with height, was calculated by dividing PEF by height. Hazard ratios (HR) for cause-specific mortality and h-PEF, adjusted for age, area of residence, smoking, and education, were calculated through Cox regression analyses. Results Of the original study population, 7068 men died from respiratory causes (non-neoplastic) and 22 490 died from other causes (including 1591 from lung cancer, 5469 from other cancers, and 10 460 from cardiovascular disease) before reaching the age of 85 years. Respiratory mortality was strongly and inversely associated with h-PEF. For h-PEF ≥ 250 L/min, the association was log-linear, with a hazard ratio (HR) of 1.29 (95% CI: 1.25–1.34) per 100 L/min reduction in h-PEF. The association was stronger but not log-linear for lower values of h-PEF. Mortality from combined other causes was also inversely associated with h-PEF, and the association was log-linear for all values of h-PEF, declining with follow-up, with HRs per 100 L/min reduction in h-PEF of 1.13 (1.10–1.15), 1.08 (1.06–1.11), and 1.06 (1.03–1.08) in three consecutive 5-year follow-up periods. Specifically, lower values of h-PEF were associated with higher mortality from cardiovascular disease and lung cancer, but not from other cancers. Conclusions A lower value of h-PEF was associated with increased mortality from respiratory and other causes, including lung cancer and cardiovascular disease, but its associations with the other causes of death declined across the follow-up period.

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Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study

Cardiovascular Diabetology ◽

10.1186/s12933-019-0953-7 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 7

Author(s):

You-Bin Lee ◽

Kyungdo Han ◽

Bongsung Kim ◽

Seung-Eun Lee ◽

Ji Eun Jun ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Cox Regression ◽

Early Mortality ◽

Hazard Ratios ◽

Epidemiological Characteristics

Abstract Background Both type 1 and type 2 diabetes are well-established risk factors for cardiovascular disease and early mortality. However, few studies have directly compared the hazards of cardiovascular outcomes and premature death among people with type 1 diabetes to those among people with type 2 diabetes and subjects without diabetes. Furthermore, information about the hazard of cardiovascular disease and early mortality among Asians with type 1 diabetes is sparse, although the clinical and epidemiological characteristics of Asians with type 1 diabetes are unlike those of Europeans. We estimated the hazard of myocardial infarction (MI), hospitalization for heart failure (HF), atrial fibrillation (AF), and mortality during follow-up in Korean adults with type 1 diabetes compared with those without diabetes and those with type 2 diabetes. Methods We used Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 in this retrospective longitudinal study. The hazard ratios of MI, HF, AF, and mortality during follow-up were analyzed using the Cox regression analyses according to the presence and type of diabetes in ≥ 20-year-old individuals without baseline cardiovascular disease (N = 20,423,051). The presence and type of diabetes was determined based on the presence of type 1 or type 2 diabetes at baseline. Results During more than 93,300,000 person-years of follow-up, there were 116,649 MIs, 135,532 AF cases, 125,997 hospitalizations for HF, and 344,516 deaths. The fully-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MI, hospitalized HF, AF, and all-cause death within the mean follow-up of 4.6 years were higher in the type 1 diabetes group than the type 2 diabetes [HR (95% CI) 1.679 (1.490–1.893) for MI; 2.105 (1.901–2.330) for HF; 1.608 (1.411–1.833) for AF; 1.884 (1.762–2.013) for death] and non-diabetes groups [HR (95% CI) 2.411 (2.138–2.718) for MI; 3.024 (2.730–3.350) for HF; 1.748 (1.534–1.993) for AF; 2.874 (2.689–3.073) for death]. Conclusions In Korea, the presence of diabetes was associated with a higher hazard of cardiovascular disease and all-cause death. Specifically, people with type 1 diabetes had a higher hazard of cardiovascular disease and all-cause mortality compared to people with type 2 diabetes.

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Association of Walnut Consumption with Total and Cause-Specific Mortality and Life Expectancy in U.S. Adults

Nutrients ◽

10.3390/nu13082699 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2699

Author(s):

Xiaoran Liu ◽

Marta Guasch-Ferré ◽

Deirdre K. Tobias ◽

Yanping Li

Keyword(s):

Life Expectancy ◽

Cox Regression ◽

Total Mortality ◽

Health Study ◽

Hazard Ratios ◽

Estimate Life Expectancy ◽

Specific Mortality ◽

Elder Adults ◽

Cvd Mortality

Walnut consumption is associated with health benefits. We aimed to (1) examine the association between walnut consumption and mortality and (2) estimate life expectancy in relation to walnut consumption in U.S. adults. We included 67,014 women of the Nurses’ Health Study (1998–2018) and 26,326 men of the Health Professionals Follow-up Study (1998–2018) who were free of cancer, heart disease, and stroke at baseline. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During up to 20 years of follow-up, we documented 30,263 deaths. The hazard ratios for total mortality across categories of walnut intake (servings/week), as compared to non-consumers, were 0.95 (95% confidence interval (CI), 0.91, 0.98) for <1 serving/week, 0.94 (95% CI, 0.89, 0.99) for 1 serving/week, 0.87 (95% CI, 0.82, 0.93) for 2–4 servings/week, and 0.86 (95% CI, 0.79, 0.93) for >=5 servings/week (p for trend <0.0001). A greater life expectancy at age 60 (1.30 years in women and 1.26 years in men) was observed among those who consumed walnuts more than 5 servings/week compared to non-consumers. Higher walnut consumption was associated with a lower risk of total and CVD mortality and a greater gained life expectancy among U.S. elder adults.

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Fruit and Vegetable Intake and Mortality in Adults undergoing Maintenance Hemodialysis

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.08580718 ◽

2019 ◽

Vol 14 (2) ◽

pp. 250-260 ◽

Cited By ~ 26

Author(s):

Valeria M. Saglimbene ◽

Germaine Wong ◽

Marinella Ruospo ◽

Suetonia C. Palmer ◽

Vanessa Garcia-Larsen ◽

...

Keyword(s):

General Population ◽

Cox Regression ◽

Vegetable Intake ◽

Fruit And Vegetable Intake ◽

Maintenance Hemodialysis ◽

Fruit And Vegetable ◽

Hazard Ratios ◽

All Cause Mortality ◽

Study Population

Background and objectivesHigher fruit and vegetable intake is associated with lower cardiovascular and all-cause mortality in the general population. It is unclear whether this association occurs in patients on hemodialysis, in whom high fruit and vegetable intake is generally discouraged because of a potential risk of hyperkalemia. We aimed to evaluate the association between fruit and vegetable intake and mortality in hemodialysis.Design, setting, participants, & measurementsFruit and vegetable intake was ascertained by the Global Allergy and Asthma European Network food frequency questionnaire within the Dietary Intake, Death and Hospitalization in Adults with ESKD Treated with Hemodialysis study, a multinational cohort study of 9757 adults on hemodialysis, of whom 8078 (83%) had analyzable dietary data. Adjusted Cox regression analyses clustered by country were conducted to evaluate the association between tertiles of fruit and vegetable intake with all-cause, cardiovascular, and noncardiovascular mortality. Estimates were calculated as hazard ratios with 95% confidence intervals (95% CIs).ResultsDuring a median follow up of 2.7 years (18,586 person-years), there were 2082 deaths (954 cardiovascular). The median (interquartile range) number of servings of fruit and vegetables was 8 (4–14) per week; only 4% of the study population consumed at least four servings per day as recommended in the general population. Compared with the lowest tertile of servings per week (0–5.5, median 2), the adjusted hazard ratios for the middle (5.6–10, median 8) and highest (>10, median 17) tertiles were 0.90 (95% CI, 0.81 to 1.00) and 0.80 (95% CI, 0.71 to 0.91) for all-cause mortality, 0.88 (95% CI, 0.76 to 1.02) and 0.77 (95% CI, 0.66 to 0.91) for noncardiovascular mortality and 0.95 (95% CI, 0.81 to 1.11) and 0.84 (95% CI, 0.70 to 1.00) for cardiovascular mortality, respectively.ConclusionsFruit and vegetable intake in the hemodialysis population is low and a higher consumption is associated with lower all-cause and noncardiovascular death.

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The Relationship between the Urinary Cadmium Concentration and Cause-Specific Mortality in Subjects without Severe Renal Damage: A 35-Year Follow-Up Study in a Cadmium-Polluted Area of Japan

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18157747 ◽

2021 ◽

Vol 18 (15) ◽

pp. 7747

Author(s):

Masaru Sakurai ◽

Yasushi Suwazono ◽

Muneko Nishijo ◽

Kazuhiro Nogawa ◽

Yuuka Watanabe ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cadmium Concentration ◽

Urinary Cadmium ◽

Risk Of Death ◽

Digestive Diseases ◽

Hazard Ratios ◽

Specific Mortality ◽

The Relationship ◽

Urinary Cadmium Concentration

We evaluated the association between urinary cadmium concentration (uCd, μg/g Cr) and risk of cause-specific mortality according to urinary β2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and β2-MG were evaluated in a survey in 1981–1982, where those participants were followed-up over 35 years later. Among the participants with a urinary β2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥ 10.0 compared with < 5.0 for cardiovascular disease [HR 1.92 (1.08–3.40) for men, 1.71 (1.07–2.71) for women], pneumonia or influenza [2.10 (1.10–4.00) for men, 2.22 (1.17–4.19) for women], and digestive diseases [for men; 3.81 (1.49–9.74)]. The uCd was significantly associated with mortality from heart failure in women and digestive diseases in men, after adjustment for other causes of death using the Fine and Gray competing risk regression model. For participants with a urinary β2-MG of ≥ 1000, no significant association was observed between uCd and any major cause of death. In the absence of kidney damage, Cd may increase the risk of death from cardiovascular disease, pneumonia, and digestive diseases.

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Association of Nut Consumption with Risk of Stroke and Cardiovascular Disease: The Million Veteran Program

Nutrients ◽

10.3390/nu13093031 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3031

Author(s):

Kerry L. Ivey ◽

Xuan-Mai T. Nguyen ◽

Rachel M. Quaden ◽

Yuk-Lam Ho ◽

Kelly Cho ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cox Regression ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Peanut Butter ◽

Veterans Affairs ◽

Hazard Ratios ◽

Artery Disease ◽

Cvd Mortality

Cardiovascular disease (CVD), including stroke and coronary artery disease (CAD), is the major cause of mortality for Americans. Nuts have been shown to improve a variety of cardiovascular disease risk factors. This study aimed to test the hypothesis that nut consumption is inversely associated with risk of incidence of stroke, CAD, and CVD mortality in the prospective Million Veterans Program (MVP). A total of 179,827 MVP participants enrolled between 2011 and 2018 were free of CVD prior to assessment of nut consumption via the food frequency questionnaire. Incident stroke and CVD events were ascertained from the Veterans Affairs electronic medical health records and the National Death Index. We used the Cox regression model to compute multivariable adjusted hazard ratios. Over the 3.5-year median follow-up, 3362 new cases of ischemic stroke were identified. When compared with participants who rarely or never consumed nuts, those consuming nuts ≥ 5 times per week were 19% less likely to experience a stroke (95% CI: 8% to 28%); 22% less likely to suffer from CAD (95% CI: 16% to 28%); and 24% less likely to die from CVD (95% CI: 7% to 37%). Consumption of peanut butter was not associated with risk of stroke. Increased dietary intake of nuts, but not peanut butter, was associated with a lower risk of stroke, CAD, and CVD death.

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Association with Longevity of Phosphatidylinositol 3-Kinase Regulatory Subunit 1 Gene Variants Stems from Protection against Mortality Risk in Men with Cardiovascular Disease

Gerontology ◽

10.1159/000515390 ◽

2021 ◽

pp. 1-9

Author(s):

Timothy A. Donlon ◽

Randi Chen ◽

Kamal H. Masaki ◽

Bradley J. Willcox ◽

Brian J. Morris

Keyword(s):

Cardiovascular Disease ◽

Life Span ◽

Mortality Risk ◽

Regulatory Subunit ◽

Phosphatidylinositol 3 Kinase ◽

Survival Curves ◽

Genotypic Effect ◽

Hazard Ratios ◽

Phosphatidylinositol 3

Introduction: Genetic variation in the phosphatidylinositol 3-kinase reregulatory subunit 1 gene (PIK3R1) is associated with longevity. Objective: The aim of the study was to determine whether cardiovascular disease (CVD) affects this association. Methods: We performed a longitudinal study of longevity-associated PIK3R1 single-nucleotide polymorphism rs7709243 genotype by CVD status in 3,584 elderly American men of Japanese ancestry. Results: At baseline (1991–1993), 2,254 subjects had CVD and 1,314 did not. The follow-up until Dec 31, 2019 found that overall, men with a CVD had higher mortality than men without a CVD (p = 1.7 × 10−5). However, survival curves of CVD subjects differed according to PIK3R1 genotype. Those with longevity-associated PIK3R1 TT/CC had survival curves similar to those of subjects without a CVD (p = 0.11 for TT/CC, and p = 0.054 for TC), whereas survival curves for CVD subjects with the CT genotype were significantly attenuated compared with survival curves of subjects without a CVD (p = 0.0000012 compared with TT/CC, and p = 0.0000028 compared with TC). Men without CVD showed no association of longevity-associated genotype with life span (p = 0.58). Compared to subjects without any CVD, hazard ratios for mortality risk were 1.26 (95% CI, 1.14–1.39; p = 0.0000043) for CT subject with CVD and 1.07 (95% CI 0.99–1.17; p = 0.097) for CC/TT subjects with CVD. There was no genotypic effect on life span for 1,007 subjects with diabetes and 486 with cancer. Conclusion: Our study provides novel insights into the basis for PIK3R1 as a longevity gene. We suggest that the PIK3R1 longevity genotype attenuates mortality risk in at-risk individuals by protection against cellular stress caused by CVD.

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Association between selenium intake, diabetes, and mortality in adults: findings from National Health and Nutrition Examination Survey (NHANES) 2003-2014

British Journal Of Nutrition ◽

10.1017/s000711452100177x ◽

2021 ◽

pp. 1-24

Author(s):

Bushra Hoque ◽

Zumin Shi

Keyword(s):

National Health ◽

Cox Regression ◽

Inverse Association ◽

Nutrition Examination Survey ◽

Health And Nutrition ◽

Hazard Ratios ◽

The Us ◽

All Cause Mortality ◽

Cvd Mortality

Abstract Selenium (Se) is a trace mineral that has antioxidant and anti-inflammatory properties. This study aimed to investigate the association between Se intake, diabetes, all-cause and cause-specific mortality in a representative sample of US adults. Data from 18,932 adults who attended the 2003-2014 National Health and Nutrition Examination Survey (NHANES) were analysed. Information on mortality was obtained from the US mortality registry updated to 2015. Multivariable logistic regression and Cox regression were used. Cross-sectionally, Se intake was positively associated with diabetes. Comparing extreme quartiles of Se intake, the odds ratio (OR) for diabetes was 1.44 (95% CI: 1.09–1.89). During a mean of 6.6 years follow-up, there were 1627 death (312 CVD, 386 cancer). High intake of Se was associated with a lower risk of all-cause mortality. When comparing the highest with the lowest quartiles of Se intake, the hazard ratios (HRs) for all-cause, CVD mortality, cancer mortality and other mortality were: 0.77 (95% CI 0.59-1.01), 0.62 (95% CI, 0.35-1.13), 1.42 (95% CI, 0.78-2.58) and 0.60 (95% CI,0.40-0.80), respectively. The inverse association between Se intake and all-cause mortality was only found among white participants. In conclusion, Se intake was positively associated with diabetes but inversely associated with all-cause mortality. There was no interaction between Se intake and diabetes in relation to all-cause mortality.

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Impact of Increasing Age on Cause-Specific Mortality and Morbidity in Patients With Stage I Non–Small-Cell Lung Cancer: A Competing Risks Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2016.69.0834 ◽

2017 ◽

Vol 35 (3) ◽

pp. 281-290 ◽

Cited By ~ 83

Author(s):

Takashi Eguchi ◽

Sarina Bains ◽

Ming-Ching Lee ◽

Kay See Tan ◽

Boris Hristov ◽

...

Keyword(s):

Lung Cancer ◽

Competing Risks ◽

Independent Predictor ◽

Forced Expiratory Volume ◽

Stage I ◽

Diffusing Capacity ◽

Curative Intent ◽

Mortality And Morbidity ◽

Competing Risks Analysis ◽

Specific Mortality

Purpose To perform competing risks analysis and determine short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who had undergone resection for stage I non–small-cell lung cancer (NSCLC). Patients and Methods Of 5,371 consecutive patients who had undergone curative-intent resection of primary lung cancer at our institution (2000 to 2011), 2,186 with pathologic stage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were included in the analysis, specifically, Charlson comorbidity index, predicted postoperative (ppo) diffusing capacity of the lung for carbon monoxide, and ppo forced expiratory volume in 1 second. Cause-specific mortality analysis was performed with competing risks analysis. Results Of 2,186 patients, 1,532 (70.1%) were ≥ 65 years of age, including 638 (29.2%) ≥ 75 years of age. In patients < 65, 65 to 74, and ≥ 75 years of age, 5-year lung cancer–specific cumulative incidence of death (CID) was 7.5%, 10.7%, and 13.2%, respectively (overall, 10.4%); noncancer-specific CID was 1.8%, 4.9%, and 9.0%, respectively (overall, 5.3%). In patients ≥ 65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer–specific CID; the higher noncancer-specific, early-phase mortality was enhanced in patients ≥ 75 years of age than in those 65 to 74 years of age. Multivariable analysis showed that low ppo diffusing capacity of lung for carbon monoxide was an independent predictor of severe morbidity ( P < .001), 1-year mortality ( P < .001), and noncancer-specific mortality ( P < .001), whereas low ppo forced expiratory volume in 1 second was an independent predictor of lung cancer–specific mortality ( P = .002). Conclusion In patients who undergo curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with an increasing impact as patient age increases.

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Plasma Vitamin B12 Levels, High-Dose Vitamin B12 Treatment, and Risk of Dementia

Journal of Alzheimer s Disease ◽

10.3233/jad-201096 ◽

2021 ◽

Vol 79 (4) ◽

pp. 1601-1612

Author(s):

Johan Frederik Håkonsen Arendt ◽

Erzsébet Horváth-Puhó ◽

Henrik Toft Sørensen ◽

Ebba Nexø ◽

Lars Pedersen ◽

...

Keyword(s):

Vitamin B12 ◽

Vascular Dementia ◽

Cox Regression ◽

Population Based ◽

High Dose ◽

Plasma Vitamin ◽

Hazard Ratios ◽

B12 Deficiency ◽

First Time

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia. Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer’s disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes). Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000–2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200–600 pmol/L). We used multivariable Cox regression to compute 0–15-year hazard ratios for dementia. Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia. Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.

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Abstract P142: The CKD273 Urinary Peptidomic Biomarker is Associated with Mortality in People at Early Stages of Diabetic Nephropathy Independent of Traditional Risk Factors

Hypertension ◽

10.1161/hyp.70.suppl_1.p142 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Gemma E Currie ◽

Sheon Mary ◽

Bernt J von Scholten ◽

Morten Lindhardt ◽

Harald Mischak ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Diabetic Nephropathy ◽

Cox Regression ◽

Outcome Data ◽

Diagnostic Purpose ◽

Urine Albumin ◽

Geometrical Mean ◽

Traditional Risk Factors

Background: Mortality in type 2 diabetes (T2D) is primarily driven by cardiovascular disease. This is amplified in diabetic nephropathy (DN), even in early ‘pre-clinical’ stages. A urinary peptidomic classifier (CKD273) has been found to predict DN development in advance of detectable microalbuminuria. Whether it is also a determinant of mortality and cardiovascular disease in patients with established albuminuria is unknown. Methods: We studied 155 subjects with T2D, albuminuria (geometrical mean [IQR]: 85 [34;194] mg/24hrs), controlled blood pressure (129±16/74±11 mmHg) and preserved renal function (eGFR 88±17 ml/min/1.73m 2 ). Blood and urine samples were collected for measurement of estimated glomerular filtration rate (eGFR), urine albumin excretion (UAE), N-terminal pro-brain natriuretic peptide (NT-proBNP; ELISA) and urinary proteomics (capillary electrophoresis coupled to mass spectrometry). Computed tomography imaging was performed to assess coronary artery calcium (CAC) score. Outcome data were collected through national disease registries over a 6 year follow up period. Results: CKD273 correlated with UAE (r=0.481, p=<0.001), age (r=0.238, p=0.003), CAC score (r=0.236, p=0.003), NT-proBNP (r=0.190, p=0.018) and eGFR (r=0.265, p=0.001). On multiple regression only UAE (β=0.402, p<0.001) and eGFR (β=-0.184, p=0.039) were statistically significant determinants. Twenty participants died during follow-up. CKD273 was a determinant of mortality (log rank [Mantel-Cox] p=0.004), and retained significance (p=0.050) after adjustment for age, sex, blood pressure, NT-proBNP and CAC score in a Cox regression model. Neither eGFR nor UAE were determinants of mortality in this cohort. Conclusions: A multidimensional biomarker can provide information on outcomes associated with its primary diagnostic purpose. Here we demonstrate that the peptidomics-based classifier CKD273 is associated with mortality in albuminuric people with T2D in even when adjusted for other established cardiovascular and renal biomarkers.

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