Table 1.
Studies assessing high-sensitive C reactive protein (hs-CRP).
| Citation | Type of Study | Quality of Study | Population | CV Outcomes | Length of Follow-Up | Main Results |
|---|---|---|---|---|---|---|
| Amit Khera, et al. Circulation. 2018 [16] | Cohort (Prospective study) | Good | Participants were middle-aged individuals (aged 40–65 years) pooled from study participants from examination 1 of the MESA study, phase 1 of the Dallas Heart Study (DHS), and the PACC study (Prospective Army Coronary Calcium Project) for the derivation cohort (n = 7382). | Non-fatal myocardial infarction (MI), non-fatal stroke, or death from coronary heart disease (CHD) or stroke. | Over a median follow-up period of 10.9 years. | A total of 304 hard ASCVD a events occurred. hs-CRP showed higher risk to the endpoint with a hazard ratio (HR) per 1 standard deviation (SD) unit (4.8) 1.1 (confidence interval (CI) 95%: 1.0–1.2, p = 0.009) |
| Marie Zöga Diederichsen et al. Atherosclerosis. 2018 [17]. | Cohort (Prospective study) | Good | A total of 1179 men and women aged 50 and 60 years from the DanRisk study. | MI, coronary revascularization procedures, stroke, ventricular arrhythmias, cardiac arrest, heart failure, heart valve surgery, significant aortic disease and significant peripheral artery disease, or death due to CVD. | A follow-up period of over 6.5 years. | A total of 73 events occurred. hs-CRP (HR 1.03, CI 95%: 1.003–1.05) was associated with CV events. Stratification by age showed hs-CRP was associated with CV events among 60-year-old subjects. Stratification by gender showed hs-CRP was associated with CV events among both males and females. |
| Da Young Lee, et al. Metabolism Clinical and Experimental. 2018 [18]. | Cohort (Prospective study) | Good | A total of 165,849 subjects aged 20 years or older who participated in the health screening programs at the Kangbuk Samsung Hospital Total Healthcare Center (or its clinics) in Seoul and Suwon, South Korea. Mean age of 39.5 (SD 9.2) years. | CVD mortality defined as ICD-10 b codes, I00-I99 (diseases of the circulatory system), including acute rheumatic fever, chronic rheumatic heart diseases, hypertensive diseases, ischemic heart diseases, cerebrovascular diseases, etc. | A mean follow-up period of 8.54 ± 1.42 years. | A total of 1316 deaths (182 from CVD) occurred. Subjects in Q4 of hs-CRP (≥1.1 mg/L c) had HR for all-cause mortality 1.40 (CI 95%: 1.18–1.66), CV mortality 1.58 (0.96–2.58) and cancer-related mortality 1.59 (1.14–1.88). The p-values for the trends between quartiles were significant (<0.05) in all three outcomes. |
| James A. de Lemos, et al. Circulation. 2018 [19]. | Cohort (Prospective study) | Good | A total of 6621 participants aged 45–84 years from the MESA study (these participants were excluded from the current analysis) and 2202 participants aged 30–65 years from the DHS study. | Non-fatal and fatal defined as ICD-10 codes, I00-I99 (diseases of the circulatory system), including acute rheumatic fever, chronic rheumatic heart diseases, hypertensive diseases, ischemic heart diseases, cerebrovascular diseases, etc., were included. | Over a median follow-up period of 10.3 years. | In the DHS study, 179 global CVD events occurred, including 96 ASCVD events. Hs-CRP in both continuous and categorical analysis (≥3 mg/L) did not have significant HR values for CV endpoint: 0.97 (0.82–1.15) and 1.06 (0.78–1.46). |
| Hugh Tunstall-Pedoe, et al. Journal American Heart Association (AHA). 2017 [20]. | Cohort (Prospective study) | Good | A total of 15,737 participants from the Scottish Heart Health Extended Cohort (SHHEC) with a mean age of 49 (SD 8.3) years. | CHD was defined as ICD 9 codes 410 to 414 and ICD 10 I20 to I25, while PAD was defined as ICD 9 440.2, 443.9, 250.6 and ICD 10 I70.2, I73.9, E10.5, E11.5, E12.5, E13.5, E14.5. | A mean follow-up period of 19.9 years. | A total of 3098 CHD events and 499 PAD events occurred. Hs-CRP showed HR 1.21 (CI 95%: 1.11–1.32). |
| Setor K. Kunutsor, et al. PLOS One. 2015 [26]. | Cohort (Prospective study) | Good | A total of 6974 participants from the PREVEND cohort were included in the current study with a mean age of 48 years old. | Cardiovascular outcomes were defined as the combined incidence of acute MI (ICD-9 code 410), acute and subacute ischemic heart disease (ICD-9 code 411), coronary artery bypass grafting (ICD-9 code 414) or percutaneous transluminal coronary angioplasty, subarachnoid hemorrhage (ICD-9 code 430), intracerebral hemorrhage (ICD-9 code 431), other intracranial hemorrhages (ICD-9 code 432), occlusion or stenosis of the precerebral (ICD-9 code 433) or cerebral (ICD-9 code 434) arteries and other vascular interventions such as percutaneous transluminal angioplasty or bypass grafting of peripheral vessels (ICD-9 code 440) and aorta (ICD-9 code 441). | A median follow-up period of 10.5 years. | A total of 737 incident CVD events were recorded, and the association of hs-CRP with incident CVD was shown. The analysis showed an HR of 1.26 (CI 95%: 1.17 to 1.38, p < 0.001), and in separate analyses for CHD and stroke, a significant association for each one was found. For categorical analysis, hs-CRP ≥ 1.23, HR 1.28 (CI 95%: 1.07 to 1.53). |
| Emily G. Kurtz, et al. Menopause. 2011 [34]. | Cohort (Prospective study) | Good | A total of 26,791 participants from the Women’s Health Study (WHS) were included in the current study, with a median age of 52.9 years old. | Non-fatal MI, non-fatal ischemic stroke (CVA), coronary revascularization procedures [coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA)], or death from CVD. | Participants were followed for a mean of 10 years for the occurrence of a first major cardiovascular event (CVE). | The total cohort was divided into hormone non-users and hormone users. Firstly, in a continuous analysis, the RR d for lnCRP was 1.27 (95%: CI, 1.13 to 1.44) for HT e non-users and 1.22 (95%: CI, 1.07 to 1.40) for HT users. In addition, the relative risk was calculated according to the quintile of CRP based on HT non-users and HT users levels and categories defined by AHA/CDC (<1 mg/L, ≥1–<3 mg/L, and ≥3 mg/L). After risk factor-adjusted RR, the highest quintile, based on HT non-users levels (>4.18 mg/L), significantly predicted CVE in HT non-users RR: 2.85 (95% CI: 1.62 to 5.00), but not in HT users. However, based on HT users levels (>6.44 mg/L), the highest quintile predicted CVE RR: 1.88 (95% CI: 1.14 to 3.11). In a fit model in which non-users with CRP< 1 mg/L were the reference group after adjusting HT users with CRP ≥3 had a RR of 1.93 (1.38–2.69), while non-users had a RR of 1.92 (1.35–2.72). |
| J. Eugen-Olsen, et al. Journal of Internal Medicine. 2010 [35]. | Cohort (Prospective study) | Fair | A total of 2602 participants from the MONICA cohort with validated suPAR levels were selected for the current study. Participants were 41, 51, 61 and 71 years old the at baseline of the study (subanalyses were carried out). | CVD outcomes were a combination of cardiovascular death (ICD-8 codes 390–448 or ICD-10 codes I00–I79 and R95–R99) ischaemic heart disease (ICD-8 codes 410–414 or ICD-10 codes I20–I25) and stroke (ICD-8 codes 431, 433 and 434 or ICD-10 codes I61 and I63). |
A median follow-up period of 12.6 years (range: 0.17–13.6). | During the follow-up period 301 incident cases of CVD were recorded. Analysis was carried out by age. After adjustment for variables included in the Frammingham risk score and suPAR, HRs for CRP > 3 mg/L and CVD in 41-year-old subjects was 1.24 (0.51–3) p = 0.63, in 51-year-old subjects was 1.78 (0.92–3.45) p = 0.09 and in 61-year-old subjects was 2.05 (1.1–3.86) p = 0.02. |
| Ulla Peterson, et al. European Journal of Cardiovascular Prevention and Rehabilitation. 2009 [38]. | Cohort (Prospective study) | Good | A total of 689 participants were selected from the baseline of the Söderåkra Cardiovascular Risk Factor study after the exclusion of participants with a history of prevalent CVD. | CV events were defined from ICD8 and ICD9 codes 410–414, 431, 433, 434, 435, 436, 437, 440, 441; and from ICD10 codes I20–I25, I61, I63-I66, I70–I72. | A follow-up period of 17 years. | A total of 69 participants died and 71 participants had a first fatal or non-fatal event during the follow-up period. HRs for hs-CRP were calculated for first major non-fatal or fatal cardiovascular events and adjusted to show an HR for hs-CRP of 1.4 (1.1–1.8) p = 0.010. |
| MH Olsen, et al. Journal of Human Hypertension. 2009 [39]. | Cohort (Prospective study) | Fair | A total of 1988 healthy subjects were included after the exclusion of 472 subjects from the baseline study with known diabetes, prior myocardial infarction or stroke. These healthy subjects were classified using HeartScore as high risk (559) and low-moderate risk (1429), depending on the expected 10-year risk of CV death above or below 5%. | Cardiovascular death, non-fatal MI or stroke. | A follow-up period of 9.5 years. | A total of 204 cardiovascular endpoint occurred during follow-up. In univarate Cox-regression analyses for hs-CRP, HRs for composite of CV endpoint and CV death in low-moderate risk subjects was 1.9 (1.0–3.5) p < 0.05 and 1.1(0.4–3.2) respectively and in high risk subjects was 1.9 (1.2–3.1) p < 0.05 and 2.5 (1.4–4.7) p < 0.01 respectively |
a atherosclerotic cardiovascular disease (ASCVD), b international classification disease (ICD-10), c milligrams/liter (mg/L), d relative risk (RR), e hormone therapy (HT).