J Hypertens. 2014 May;32(5):1034-41;

Association between albuminuria, atherosclerotic plaques, elevated pulse wave velocity, age, risk category and prognosis in apparently healthy individuals.

Greve SV, Blicher MK, Blyme A, Sehestedt T, Hansen TW, Rassmusen S, Vishram JK, Ibsen H, Torp-Pedersen C, Olsen MH.

Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology, Odense University Hospital.



METHOD: Two thousand and fifty-nine healthy individuals aged 41, 51, 61 and 71 years examined in 1993, were divided in age, SCORE and Framingham risk score (FRS) groups. Subclinical vascular damage (SVD) was defined as carotid-femoral pulse wave velocity (cfPWV) at least 12 m/s, carotid atherosclerotic plaques or albuminuria defined as urine albumin/creatinine ratio at least 90th percentile of 0.73/1.06 mg/mmol men/women. In 2006, the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for ischemic heart disease was recorded (n = 229).

RESULTS: With increasing age, SCORE or FRS risk group, prevalence of cfPWV at least 12 m/s (5.2, 14.5, 35.3, 53.5% or 4.4, 15.6, 50.9, 66.1% or 4.0, 9.5, 32.1, 56.1%), atherosclerotic plaque (4.0, 19.0, 35.3, 53.5% or 3.5, 16.8, 43.7, 55.9%, or 6.6, 7.6, 9.8, 20.0%) and albuminuria (7.9, 8.7, 11.4, 20.6% or 7.9, 8.2, 16.6, 19.5% or 6.6, 7.6, 9.8, 20.0%) increased, all P < 0.001.CEP was associated with albuminuria in individuals aged 61 or 71 years, with moderate or very high SCORE or intermediate or high FRS (all P < 0.05), with atherosclerotic plaques in individuals aged 41, 51 or 61 years, with moderate SCORE or with high-intermediate or high FRS (all P < 0.01), and with cfPWV at least 12 m/s in individuals aged 51 years (P < 0.001) or high FRS (P < 0.05). Presence of at least one SVD was significantly associated with an increased risk in individuals aged 51 [hazard ratio 2.7 (1.6-4.8)] and 61 years [hazard ratio 2.7 (1.5-4.7)], moderate [hazard ratio 2.4 (1.6-3.7)] or high SCORE risk group [hazard ratio 2.3 (1.2-4.7)] and low-intermediate [hazard ratio 3.3 (1.5-7.0)], high-intermediate [hazard ratio 2.3 (1.5-3.5)] and high FRS risk group [hazard ratio 2.0 (1.4-3.0)].

CONCLUSION: SVD and especially atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 0.73/1.06 mg/mmol (men/women) added prognostic information in individuals aged 51 or 61 years or with moderate or intermediate risk.

PMID: 24621803


Supplements (written by Sara V Greve and Michael H. Olsen)

To estimate a person’s risk for cardiovascular disease (CVD) the traditional risk factors sex, age, blood pressure, cholesterol and smoking habits are often used. Systemic COronary Risk Evaluation (SCORE) is a risk chart that uses these traditional risk factors to calculate the risk for cardiovascular death during the next ten years and classifies persons in low-, moderate-, high- and very high cardiovascular risk groups (1). Framingham Heart Score (FSH) is a similar risk chart which uses the same traditional risk factors together with diabetes to classify persons in low-, low intermediate-, high intermediate and high risk of myocardial infarction, ischemic heart disease, peripheral artery disease and cerebral events like stroke or transitory cerebral ischemia (2). Lifestyle intervention is generally recommended in subjects with moderate SCORE risk and medical preventive treatment in subjects with high SCORE risk.

Traditional risk factors are very good to estimate cardiovascular risk in groups but not (3) in individuals (4). A large part of subjects suffering their first cardiovascular event has actually low cardiovascular risk and is therefore not eligible for prevention (5).

Subclinical vascular damage (SVD) is damages in the vascular system that can be measured before CVD occur. SVD predict cardiovascular disease independently of traditional risk factors (6-9), probably because SVD reflect the individual susceptibility for the harmful effect of traditional risk factors like elevated blood pressure, age, cholesterol and smoking habits. This is why SVD might supplement SCORE and FRS in the prediction of CVD in individuals.

In order to improve prediction of CVD in individuals we investigated the coexistence and prognostic value of urine albumin/creatinine ratio (UACR) above the 90% percentile of 0.73mg/mmol in men and 1.06 mg/mmol in women, presence of atherosclerotic plaques in the carotid arteries and elevated pulse wave velocity (PWV) >12m/s (a measure of arterial stiffness), three commonly used markers of SVD, in different age and risk groups.

In 1993-1994, 2656 persons accepted participation in a population survey measuring traditional risk factors and these three measures of SVD. For the present study we have excluded persons with known CVD or in treatment for hypertension, CVD or diabetes. This left 2059 persons who were divided in age groups (41, 51, 61 and 71), SCORE- and FRS risk groups. In 2006 a combined cardiovascular endpoint (CEP) of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for ischemic heart disease was registered from national registered.

This study showed that the prevalence of SVD increased with higher age, SCORE- and FRS risk. From the youngest to the oldest elevated PWV and presence of atherosclerotic plaques in the carotid arteries increased 13-fold, whereas elevated UACR increased 2.5-fold. Prevalence of atherosclerotic plaques increased especially between age 41 and 51. Prevalence of elevated PWV increase steadily with age whereas elevated UACR primarily increased after the age of 51. The same pattern of change in prevalence of the different SVD was observed in different FRS and SCORE risk groups.

The risk of CEP increased with increasing numbers of SVD, except in individuals aged 71 years, having very high SCORE risk or low-intermediate FRS risk (Figure). Presence of atherosclerotic plaques or elevated UACR, but not elevated PWV was associated with higher risk of CEP independently of age, sex, smoking status, heart rate, blood pressure and cholesterol.

Further studies of this population have shown that elevated UACR and presence of atherosclerotic plaques in the carotid arteries can reclassify a significant number of persons with moderate SCORE risk one risk category up, changing their indication for primary prevention with potentially cost-effective impact on health (10).

In conclusion, with older age and higher risk category the prevalence of SVD increased. The rate of CEP increased with rising number of SVD and the rate of CEP was especially associated with elevated UACR and presence of atherosclerotic plaques which seems able to improve individual risk prediction with potentially beneficial effects on health.

SG fig1 SG fig2 SG fig3


  1. Conroy RM, Pyorala K, Fitzgerald AP, Sans S, Menotti A, De Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. European heart journal. 2003 Jun;24(11):987-1003. PubMed PMID: 12788299.
  2. D’Agostino RB, Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008 Feb 12;117(6):743-53. PubMed PMID: 18212285.
  3. Magnus P, Beaglehole R. The real contribution of the major risk factors to the coronary epidemics: time to end the “only-50%” myth. Archives of internal medicine. 2001 Dec 10-24;161(22):2657-60. PubMed PMID: 11732929.
  4. Stamler J, Stamler R, Neaton JD, Wentworth D, Daviglus ML, Garside D, et al. Low risk-factor profile and long-term cardiovascular and noncardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women. JAMA : the journal of the American Medical Association. 1999 Dec 1;282(21):2012-8. PubMed PMID: 10591383.
  5. Akosah KO, Schaper A, Cogbill C, Schoenfeld P. Preventing myocardial infarction in the young adult in the first place: how do the National Cholesterol Education Panel III guidelines perform? Journal of the American College of Cardiology. 2003 May 7;41(9):1475-9. PubMed PMID: 12742284.
  6. Sehestedt T, Jeppesen J, Hansen TW, Wachtell K, Ibsen H, Torp-Pedersen C, et al. Risk prediction is improved by adding markers of subclinical organ damage to SCORE. European heart journal. 2010 Apr;31(7):883-91. PubMed PMID: 20034972.
  7. Jensen JS, Feldt-Rasmussen B, Strandgaard S, Schroll M, Borch-Johnsen K. Arterial hypertension, microalbuminuria, and risk of ischemic heart disease. Hypertension. 2000 Apr;35(4):898-903. PubMed PMID: 10775558.
  8. Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K, et al. Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex. Journal of hypertension. 2008 Jan;26(1):26-34. PubMed PMID: 18090537.
  9. Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K, et al. New risk markers may change the HeartScore risk classification significantly in one-fifth of the population. Journal of human hypertension. 2009 Feb;23(2):105-12. PubMed PMID: 18784734.
  10. Greve SV, Blicher MK, Sehestedt T, Rasmussen S, Eva-Marie Gram-Kampmann et al. Effective risk stratification in patients with moderate cardiovascular risk using albuminuria and atherosclerotic plaques in the carotis arteries. Acceptet 2015 May; Journal of Hypertension.
Multiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier SchönmannMultiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier Schönmann