The risk and added values of the atherosclerotic cardiovascular risk enhancers on prediction of cardiovascular events: Tehran lipid and glucose study

Abstract

Background In 2013 American College of Cardiology and the American Heart Association released a guideline on the management of atherosclerotic cardiovascular disease (ASCVD) including a composite of death from CVD, non-fatal myocardial infarction, or non-fatal stroke (hard CVD). This guideline recommended a risk score that was calculated using pooled cohort equations (ASCVD-PCE). The guideline was updated in 2018/2019 and further risk discussion was suggested for deciding whether to continue or initiate statin therapy among non-diabetic individuals with ASCVD-PCE score ranged 5–20%. They recommended a risk discussion with considering risk enhancing factors (ASCVD-REFs) including family history of premature CVD, chronic kidney disease, triglycerides ≥ 175 mg/dl, low-density lipoprotein cholesterol (LDL-C) ≥ 160 mg/dl, metabolic syndrome (Mets), and for women premature menopause, and hypertensive disorders of pregnancy (HDP). In the current study, we aimed to examine the predictability of recommended ASCVD-REFs on incident hard CVD in non-diabetic individuals with LDL-C 70-189 mg/dl, with ASCVD-PCE risk 5–20% during 10 and 15-year follow-up. Methods Among a total of 3546 non-diabetic individuals aged 40-75 years, after excluding those with ASCVD-PCE score < 5% and ≥ 20% (n = 2342), 1204 individuals (women = 332) were included. The univariable and multivariable (further adjusted for ASCVD-PCE) Cox regression analysis were used to evaluate the association of each potential ASCVD-REFs with hard CVD. Additionnaly, the role of different components of Mets and a history of gestational diabetes (GDM)/macrosomia was also examined. The predictive ability of each significant ASCVD-REFs, then was evaluated by the discrimination accuracy and risk reclassification index. Results During the 10-year follow-up, 73 hard CVD events occurred. Although in univariable analysis, high blood pressure (BP) component of Mets, GDM/macrosomia, and HDP remained as significant ASCVD-REFs, in the multivariable analysis, only the history of HDP (5.35 (1.22–23.38)) and GDM/macrosomia (3.18 (1.05–9.65)) showed independent risks. During the 15-year follow-up, Mets (1.47 (1.05–2.06)) and its components of high waist circumference (1.40 (1.0–1.95)) and high BP (1.52 (1.07–2.15)) significantly increased the risk. These ASCVD-REFs did not improve discrimination or predictive ability. Conclusions In a decade follow-up, only conditions specific for women and in longer follow-up, the presence of Mets perse, and its components of high WC and high BP were shown as significant ASCVD-REFs.

Assessment of Cardiovascular Risk in Women: Progress so Far and Progress to Come

“… ever pregnant 10-y CVD age at menarche/menopause, menopausal status, HRT, gestational hypertension/diabetes, number of children, miscarriages, stillbirths b C-index 0.70 (0.67, 0.73) 0.70 (0.67, 0.73) – n.s. TLGS (1) 90 – 10-y CVD hypertensive disorders of pregnancy C-index 0.52 (0.42, 0.61) 0.56 (0.49, 0.63) – – – 10-y CVD gestational diabetes, macrosomia C-index 0.52 (0.42, 0.61) 0.60 (0.48, 0.74) – – TLGS (2) 89 – 19-y CVD placenta previa/abruption, preterm delivery, abortion, stillbirth, pregnancy-induced hypertension/pre-eclampsia, gestational diabetes, ectopic pregnancy c C-index 0.7798 (0.7602, 0.7974) 0.7851 (0.7677, 0.8041) – <0.001 VIP 91 – 10-y CVD low birth weight offspring C-index 0.69 (0.67, 0.71) 0.69 (0.67, 0.71) 0.002 (−0.001, 0.006) – – 10-y CVD hypertensive disorders of pregnancy C-index 0.69 (0.67, 0.71) …”

“…In addition, we screened reference lists of relevant articles to identify additional publications and found one further article. Among the 91 identified articles, nine [84][85][86][87][88][89][90][91][92] examined the added value of pregnancy-or reproductive-factors to already existing cardiovascular risk scores. An overview of the studies identified by our literature search is provided in Table 3.…”

Prevalence and significance of risk enhancing biomarkers in the United States population at intermediate risk for atherosclerotic disease

“…The metabolic syndrome (14) is a prime example of how a multiplicity of biomarkers can together predict ASCVD independently of the major risk factors (15)(16)(17)(18). Among its components are dyslipidemia, pro-inflammatory state, prothrombotic state, moderately elevated blood pressure, and dysglycemia/insulin resistance.…”

“…Many of them can be considered metabolic risk factors, the same as or similar those as the metabolic syndrome (a multiplex risk factor for ASCVD (19) and a designated risk enhancing factor (20). An increased waist circumference is one independent predictor in the metabolic syndrome (18). Recent cholesterol guidelines (4) recognized moderate elevations of non-HDL-C, LDL-C, or apoB as a risk biomarker (Figure 5); since these 3 factors are highly correlated, the presence of more than one should not be double counted.…”

Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?

“…Accordingly, in a study involving 47 metastatic melanoma patients treated with ipilimumab and RT, the abscopal effect emerged as being more successful with a reasonably hypo-fractionated dose inferior to 3 Gy compared to a dose higher than 3 Gy, which impaired the abscopal effect by abolishing cell-mediated immune responses [ 107 ]. In conclusion, all these observations suggest that radiation dosage and partition, along with the distinctive TME features, contribute to explaining the double-edged sword represented by RT in terms of immunoenhancement or immunosuppression [ 108 ]. More in-depth individual analyses are needed, together with reliable patient response markers, to identify how irradiation in combination with ICIs can be optimally turned into a therapeutic advantage [ 36 , 109 , 110 ], leaving open the option of a purinergic pathway blockade.…”