Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex.

BACKGROUND: Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated the impact of age and sex on their prognostic performance in a subgroup of 1994 apparently healthy individuals without diabetes, previous stroke or myocardial infarction, who did not receive any cardiovascular, antidiabetic or lipid-lowering medication. METHODS: In 1993-1994 we recorded cardiovascular risk factors, UACR, hsCRP and Nt-proBNP. The composite cardiovascular endpoint (CEP) of cardiovascular death and non-fatal stroke or myocardial infarction was assessed after 9.5 years. RESULTS: In Cox regression analyses predicting CEP, the effects of log(hsCRP) and log(Nt-proBNP) were modulated by sex (P < 0.05) and age (P < 0.05), respectively. The effect of logUACR was not significantly modulated by age or sex. Log(hsCRP)/SD did not predict CEP in women, but did predict CEP in 41 plus 51-year-old men [hazard ratio (HR) 1.71; 95% confidence interval, 1.1-2.6; P < 0.05] and 61 plus 71-year-old men (HR 1.64; 1.3-2.2; P < 0.001). Log(Nt-proBNP)/SD predicted CEP in 61 plus 71-year-old women (HR 1.74; 1.2-2.5; P < 0.01) and in 61 plus 71-year-old men (HR 1.58; 1.3-2.0; P < 0.001). CONCLUSION: Elevated hsCRP, reflecting early atherosclerosis, predicted CEP even in 41 plus 51-year-old men. Elevated Nt-proBNP, reflecting subclinical cardiovascular damage, predicted CEP in 61 plus 71-year-old subjects. Elevated UACR, reflecting endothelial dysfunction as well as microvascular damage, predicted events independently of age and sex, but primarily in 61 plus 71-year-old subjects.

N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population.

AIM: Serum N-terminal pro-brain natriuretic peptide (Nt-proBNP), high sensitivity (hs)-C-reactive protein, and urine albumin/creatinine ratio (UACR) are cardiovascular (CV) risk markers in the general population. The aim of this study was to determine whether they predicted CV events independently of established CV risk factors and whether they did so in an additive fashion. METHODS AND RESULTS: In a population-based sample of 2656 individuals, 41, 51, 61, and 71 years old, we measured UACR, serum Nt-proBNP, hs-C-reactive protein, insulin, lipids and plasma glucose, clinic blood pressures, body composition, left ventricular (LV) mass index, and ejection fraction (EF) by echocardiography and pulse wave velocity. During the following 9.4 years, the combined CV endpoint (CEP) of CV death (136), non-fatal stroke, or non-fatal myocardial infarction occurred in 219 subjects. After adjustment for established CV risk factors using Cox-regression analyses, CEP and CV death were predicted by log(Nt-proBNP)/SD [hazard ratio (HR) = 1.58 and HR = 1.80, both P < 0.001] and by log(UACR)/SD (HR = 1.44 and HR = 1.52, both P < 0.001) in an additive fashion, but not by log(hs-C-reactive protein)/SD (HR = 1.17, P = 0.06 and HR = 1.13, NS). CV risk functions were constructed on the basis of Cox-regression analyses. Inclusion of Nt-proBNP and UACR did not increase the area under the receiver-operating characteristic plots. CONCLUSION: Serum Nt-proBNP and UACR, but not hs-C-reactive protein, predicted CV events after adjustment for established CV risk factors including LV EF and relative wall thickness. However, more studies in relevant subgroups are needed before Nt-proBNP and UACR can be recommended for risk prediction in the general population to select subjects for primary prevention.

Does long-term losartan- vs atenolol-based antihypertensive treatment influence collagen markers differently in hypertensive patients? A LIFE substudy.

BACKGROUND: The aim of this study was to investigate the effects of losartan- vs atenolol-based antihypertensive treatment on circulating collagen markers beyond the initial blood pressure (BP) reduction. METHODS: In 204 patients with hypertension and left ventricular (LV) hypertrophy we measured serum concentration of carboxy-terminal telopeptide of type I procollagen (ICTP), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), amino-terminal propeptide of type I procollagen (PINP) and LV mass by echocardiography at baseline and annually during 4 years of losartan- or atenolol-based antihypertensive treatment; 185 patients completed the study. RESULTS: Beyond the first year of treatment systolic and diastolic BP, LV mass index (LVMI) as well as collagen markers did not change significantly and were equal in the two treatment groups. Changes in PICP during first year of treatment were related to subsequent changes in LV mass index after 2 and 3 years of treatment (r=0.28 and r=0.29, both p<0.05) in patients randomized to losartan, but not atenolol. CONCLUSION: Long-term losartan- vs atenolol-based antihypertensive treatment did not influence collagen markers differently, making a BP-independent effect of losartan on collagen markers unlikely. However, initial reduction in circulating PICP may predict later regression of LV hypertrophy during losartan-based antihypertensive treatment.

High-sensitivity C-reactive protein is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors.

BACKGROUND: The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors. METHODS: In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction]. RESULTS: Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001). CONCLUSION: After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.

N-terminal pro brain natriuretic peptide is inversely related to metabolic cardiovascular risk factors and the metabolic syndrome.

We wanted to investigate the relationship of N-terminal pro brain natriuretic peptide (Nt-proBNP) to metabolic and hemodynamic cardiovascular (CV) risk factors in the general population. From a population-based sample of 2656 people 41, 51, 61, or 71 years of age, we selected 2070 patients without previous stroke or myocardial infarction who did not receive any CV, antidiabetic, or lipid-lowering treatment in 1993 to 1994. Traditional CV risk factors, 24-hour blood pressures, left ventricular (LV) mass, and ejection fraction by echocardiography, pulse wave velocity, urine albumin/creatinine ratio (UACR), and serum Nt-proBNP were measured in 1993 to 1994. The metabolic syndrome was defined in accordance with the definition of the European Group for the Study of Insulin Resistance (EGIR). Higher log(Nt-proBNP) was in multiple regression analysis related to female gender (beta=-0.37), older age (beta=0.32), higher clinic pulse pressure (beta=0.20), lower serum total cholesterol (beta=-0.15), lower LVEF (beta=-0.08, all P<0.001), lower log(serum insulin) (beta=-0.07), lower log(plasma glucose) (beta=-0.06, both P<0.01, lower log(serum triglyceride) (beta=-0.06), lower body mass index (beta=-0.05); lower heart rate (beta=-0.05), higher logUACR (beta=0.04, all P<0.05) and higher log(LV mass index) (beta=0.04, P=0.07), adjusted R2=0.35, P<0.001). The metabolic syndrome was associated with lower Nt-proBNP (35 pg/mL versus 48 pg/mL; P<0.001) and shifted the positive relationship between pulse pressure and Nt-proBNP to the right (ie, higher blood pressure for a given level of Nt-proBNP). The metabolic syndrome was associated with lower Nt-proBNP levels and shifted the positive relationship between Nt-proBNP and pulse pressure to the right, creating a possible link between the metabolic syndrome and hypertension.