A nonlinear association of total cholesterol with all-cause and cause-specific mortality

Abstract

Background The link between total cholesterol (TC) and all-cause and specific mortality has not been elucidated. Herein, we aimed to evaluate the effect of TC levels on all-cause, cardiovascular disease (CVD), and cancer mortality. Methods All data analyzed were obtained from the National Health and Nutrition Examination Survey 1999–2014. The relationship between levels of TC and mortality was determined through Cox proportional hazard regression analysis coupled with multivariable adjustments. Two-piecewise linear regression models and Cox models with penalized splines were applied to explore nonlinear and irregular shape relationships. Kaplan–Meier survival curve and subgroup analyses were conducted. Results The sample studied comprised 14,662 men and 16,025 women, categorized as 25,429 adults aged 18–65 and 5,258 adults over 65 years old. A total of 2,570 deaths were recorded. All-cause, cardiovascular, and cancer mortality showed U-curve associations after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause and cancer mortality were particularly negatively related to TC levels in the lower range < 200 mg/dL, especially in the range < 120 mg/dL (HR 1.97; 95% CI 1.38, 2.83, HR 2.39; 95% CI 1.21, 4.71, respectively). However, the HRs of cardiovascular disease mortality in the range < 120 mg/dL were the lowest (HR 0.60; 95% CI 0.15, 2.42). In the upper range, a TC range of ≥ 280 mg/dL was correlated with mortality as a result of CVD and cancer (HR 1.31; 95% CI 0.87, 1.97 and HR 1.22; 95% CI 0.82, 1.79). The lowest cumulative survival rate of all-cause mortality was recorded in the lowest TC-level group, while the lowest cumulative survival rate of CVD mortality was recorded in the highest TC-level group. Conclusions A nonlinear association of TC level with all-cause, cancer, and CVD mortality in the American population was observed, suggesting that too low or too high serum total cholesterol levels might correlate with adverse outcomes.

Inverse Association between Statin Use and Cancer Mortality Relates to Cholesterol Level

“…Cholesterol level and the risk of cancer death have been shown to obey a U-curve association. An especially low cholesterol level has been linked to an increased risk of cancer death in previous studies [ 9 , 10 ], but similarly to the results from studies assessing the association between cholesterol level and the risk of cancer, these studies are prone to reverse causation bias.…”

Association of Controlling Nutritional Status Score With Adverse Outcomes in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis

“…Particularly, too low, or too high total cholesterol level was independently correlated with adverse outcomes. 33,34 For these reasons, combination of serum albumin, lymphocyte count, and total cholesterol level may synergetic improve their prognostic significance. Also, the component of CONUT score can reflect protein, inflammation, and lipid metabolism.…”

“…Aggressive statin therapy should be used with caution among CAD patients with higher CONUT score because a nonlinear association of total cholesterol with adverse outcomes may be present. 34 Considering the high prevalence and negative impact of malnutrition on prognosis, CAD patients with high CONUT scores should be monitored and receive nutritional management. However, there is still a lack of clinical evidence to support the beneficial effect of nutritional intervention in these malnourished patients.…”

Predicting All-Cause Mortality Risk in Atrial Fibrillation Patients: A Novel LASSO-Cox Model Generated From a Prospective Dataset

“…In this LASSO-Cox model, not taking statins is an independent risk factor for AF-associated death. As recently reported, the levels of total cholesterol (TC) are non-linearly associated with all-cause mortality, as well as cancer and cardiovascular disease mortality, in the American population (42). Thus, it is necessary to maintain TC in a moderate range by statin medication.…”