Residual cardiovascular risk: When should we treat it? Gomez-Delgado, Francisco; Raya-Cruz, Manuel; Katsiki, Niki ...
European journal of internal medicine,
February 2024, 2024-Feb, 2024-02-00, 20240201, Letnik:
120
Journal Article
Recenzirano
•Residual cardiovascular (CV) risk constitutes a complex issue with many factors involved.•Residual CV risk factors include: triglyceride-rich lipoproteins (TRLs), remnant cholesterol (RC), ...lipoprotein (a): Lp (a) and inflammation.•Healthy habits as Mediterranean diet and physical activity modulate residual CV risk.•Apolipoprotein C-III (apoC-III) and angiopoietin-related protein 3 (ANGPTL3) inhibitors to reduce TRLs and RC could modulate residual CV risk.•Antisense oligonucleotides (ASO), small-interfering ribonucleic acid (siRNA) and oral agents (Muvalaplin) reduce Lp(a) modulating residual CV risk.
Cardiovascular disease (CVD) still being the most common cause of death in worldwide. In spite of development of new lipid-lowering therapies which optimize low-density lipoprotein cholesterol (LDL-c) levels, recurrence of CVD events implies addressing factors related with residual cardiovascular (CV) risk. The key determinants of residual CV risk include triglyceride-rich lipoproteins (TRLs) and remnant cholesterol (RC), lipoprotein(a) Lp(a) and inflammation including its biochemical markers such as high sensitivity C reactive protein (hs-CRP). On the other hand, unhealthy lifestyle habits, environmental pollution, residual thrombotic risk and the residual metabolic risk determined by obesity and type 2 diabetes (T2D) have a specific weight in the residual CV risk. New pharmacologic therapies and pathways are being explored such as inhibition of apolipoprotein C-III (apoC-III) and angiopoietin-related protein 3 (ANGPTL3) in order to explore if a reduction in TRLs and RC reduce CVD events. Therapeutic target of inflammation plays an attractive way to reduce the atherosclerotic process and to date, approved therapies as colchicine plays a beneficial effect in chronic inflammation and residual CV risk. Lp(a) constitutes one of the most residual CV risk factor due to linkage with CVD and aortic valve stenosis. New and hopeful treatments including antisense oligonucleotides (ASO) and small-interfering ribonucleic acid (siRNA) which interfere in LP(a) codification have been developed to achieve an adequate control in Lp(a) levels. This review points out the paradigms of residual CV risk, discus how we should manage their features and summarize the different therapies targeting each residual CV risk factor.
Scope
It is hypothesized that decreased advanced glycation end products (AGEs) levels could affect type 2 diabetes mellitus (T2DM) remission in newly diagnosed patients through the consumption of two ...healthy diets.
Methods and Results
Patients from CORDIOPREV study, all with previous cardiovascular events, with T2DM at the beginning of the study are included. Patients are randomized to a Mediterranean or a low‐fat diet for five years. No different diabetes remission rates are found among diets. Serum methylglioxal (MG) and carboximethyllysine (CML), levels dietary AGE, as well as gene expression of AGER1 and RAGE are measured. Serum MG decreases only after the consumption of the Mediterranean diet. Moreover, a COX regression analysis shows that each SD decrease in the MG, occurring after the Mediterranean diet, increases the probability of T2DM remission with HR:2.56(1.02–6.25) and p = 0.046 and each SD increase in disposition index at baseline increases the probability of remission with HR:1.94(1.32–2.87) and p = 0.001.
Conclusions
It is demonstrated that the reduction of serum AGEs levels and the modulation of its metabolism, occurring after the consumption of a Mediterranean diet, might be involved in the molecular mechanism underlying the T2DM remission of newly diagnosed patients with coronary heart disease.
A Mediterranean diet reduces serum levels of advanced glycation end products (AGEs) (mainly methylglioxal, MG), reducing dietary AGEs and modulating AGE metabolism. Patients who reduce MG levels after this diet have a higher probability of type 2 diabetes mellitus (T2DM) remission. Serum AGE reduction might be involved in the molecular mechanism underlying diabetes remission of T2DM patients with coronary heart disease.
Background
We try to explore whether long‐term consumption of two healthy dietary patterns (low‐fat LF diet or Mediterranean diet MedDiet) interacts with the apolipoprotein E (APOE) single‐nucleotide ...polymorphisms (SNPs: rs439401, rs440446 and rs7412) modulating postprandial hypertriglyceridemia (ppHTG) in coronary heart disease (CHD) patients.
Methods and results
We selected patients from the CORDIOPREV study with genotyping and who underwent an oral fat load test (FLT) at baseline and after 3 years follow‐up (n = 506). After 3 years of follow‐up, we found a gene‐diet interaction between the APOE rs439401 SNP and MedDiet. Specifically, T‐allele carriers in the MedDiet group showed a more significant decrease in postprandial triglycerides (TG: P = 0.03) and large triacylglycerol‐rich lipoproteins (TRLs) TG (large TRLs TG; P = 0.01) compared with CC subjects. Consistently, the area under the curve of TG (AUC‐TG; P‐interaction = 0.03) and AUC‐large TRLs TG (P‐interaction = 0.02) were significantly lower in T‐allele carriers compared with CC subjects.
Conclusions
The long‐term consumption of a MedDiet modulates ppHTG through APOE genetic variants in CHD patients. This gene‐diet interaction may contribute to a more precise dietary advice in CHD patients.
Background and objectives
A Mediterranean lifestyle may prevent and mitigate cardiometabolic disorders. We explored whether adherence to a Mediterranean lifestyle was prospectively associated with ...the risk of metabolic syndrome (MetS) among coronary heart disease (CHD) patients.
Methods
The Coronary Diet Intervention with Olive Oil and Cardiovascular Prevention (CORDIOPREV) study was an interventional diet study to compare a Mediterranean diet with a low‐fat diet, in 1002 CHD patients. The Mediterranean lifestyle (MEDLIFE) index was used to assess adherence to a MEDLIFE at baseline, and after 5 years, in 851 participants from the CORDIOPREV study. Subjects were classified as having high (>13 points), moderate (12–13 points), and low (<12 points) adherence to the MEDLIFE. Multivariable logistic regression models were used to determine the association between MEDLIFE adherence and the risk of MetS development or reversal.
Results
During the 5‐year follow‐up, CORDIOPREV participants with high adherence to MEDLIFE had a lower risk of MetS development (odds ratio OR 0.37, 95% confidence interval CI 0.19–0.75, p < 0.01) and a higher likelihood of reversing preexisting MetS (OR 2.08 CI 95% 1.11–3.91, p = 0.02) compared with participants in the low MEDLIFE adherence group. Each additional one‐point increment in the MEDLIFE index was associated with a 24% lower risk of MetS development (OR 0.76, 95% CI 0.64–0.90, p < 0.01) and a 21% higher likelihood of reversing preexisting MetS (OR 1.21 CI 95% 1.04–1.41, p = 0.01).
Conclusions
Our results showed that greater adherence to a MEDLIFE reduced the risk of subsequent MetS development and increased the likelihood of reversing preexisting MetS among patients with CHD at baseline.
Scope
The differences between the baseline gut microbiota of patients who developed type 2 diabetes (T2D) consuming a low‐fat (LF) or a Mediterranean (Med) diet are explored and risk scores are ...developed to predict the individual risk of developing T2D associated with the consumption of LF or Med diet.
Methods and Results
All the patients from the CORDIOPREV study without T2D at baseline (n = 462) whose fecal sample are available, are included. Gut microbiota is analyzed by 16S sequencing and the risk of T2D after a median follow‐up of 60 months assessed by Cox analysis. Linear discriminant analysis effect size (LEfSe) analysis shows a different baseline gut microbiota in patients who developed T2D consuming LF and Med diets. A higher abundance of Paraprevotella, and lower Gammaproteobacteria and B. uniformis are associated with T2D risk when an LF diet is consumed. In contrast, higher abundances of Saccharibacteria, Betaproteobacteria, and Prevotella are associated with T2D risk when a Med diet is consumed.
Conclusion
The results suggest that different interactions between the microbiome and dietary patterns may partially determine the risk of T2D development, which may be used for selecting personalized dietary models to prevent T2D.
Gut microbiome may play a role in the different responses to dietary interventions. The results suggest that different interactions between the microbiome and dietary patterns may partially determine the risk of type 2 diabetes development according to the diet who is going to be consumed, which may be used for selecting personalized dietary models to prevent type 2 diabetes.
Cardiovascular disease remains the commonest health problem in developed countries, and residual risk after implementing all current therapies is still high. The use of marine omega-3 fatty acids ...(DHA and EPA) has been recommended to reduce cardiovascular risk by multiple mechanisms.
To update the current evidence on the influence of omega-3 on the rate of cardiovascular events.
We used the MEDLINE and EMBASE databases to identify clinical trials and randomized controlled trials of omega-3 fatty acids (with quantified quantities) either in capsules or in dietary intake, compared to placebo or usual diet, equal to or longer than 6 months, and written in English. The primary outcome was a cardiovascular event of any kind and secondary outcomes were all-cause mortality, cardiac death and coronary events. We used RevMan 5·1 (Mantel-Haenszel method). Heterogeneity was assessed by the I2 and Chi2 tests. We included 21 of the 452 pre-selected studies.
We found an overall decrease of risk of suffering a cardiovascular event of any kind of 10 % (OR 0·90; 0·85-0·96, p = 0·001), a 9 % decrease of risk of cardiac death (OR 0·91; 0·83-0·99; p = 0·03), a decrease of coronary events (fatal and non-fatal) of 18 % (OR 0·82; 0·75-0·90; p < 1 × 10⁻⁴), and a trend to lower total mortality (5 % reduction of risk; OR 0·95; 0·89-1·02; p = 0·15. Most of the studies analyzed included persons with high cardiovascular risk.
marine omega-3 fatty acids are effective in preventing cardiovascular events, cardiac death and coronary events, especially in persons with high cardiovascular risk.
Scope
Insulin resistance (IR) and chronic low‐grade inflammation are hallmarks of type 2 diabetes mellitus (T2DM). The “NOD‐like receptor pyrin domain containing‐3” (NLRP3) inflammasome component of ...innate immunity is a metabolic stress sensor modulated by dietary and genetics factors. The aim of this study was to evaluate the effects of the consumption of two diets for 3 years, Mediterranean (Med) and low fat, on glucose homeostasis in the 1002 coronary heart disease patients of the CORDIOPREV study, according to a genetic variant of NLRP3 inflammasome.
Methods and results
The study was conducted in the framework of the CORDIOPREV study, a randomized dietary intervention with Med and low‐fat diets. Single nucleotide polymorphisms (SNPs) located at inflammasome NLRP3 gene were genotyped by OpenArray platform. Nondiabetic CT+TT carriers of the rs4612666 SNP and AG+AA carriers of the rs10733113 SNP increased insulin sensitivity index (ISI) after 3 years of dietary intervention, whereas no effect was observed in diabetic patients. Further analysis by diet showed that the improvement of the ISI in nondiabetic rs10733113 AG+AA carriers was specific to the consumption of the Med diet.
Conclusion
Our results show that the benefits associated with a Med diet regarding glucose homeostasis in non‐T2DM patients depend on genetic variation in the inflammasome.
NLRP3 inflammasome activation specifically induces IL‐1β inflammation, which in turn leads to insulin resistance and progression of type 2 diabetes. It is shown that rs10733113 A allele carriers improve the insulin sensitivity after 3 years of Mediterranean (Med) diet consumption, presumably by dietary MUFA‐inflammasome gene variant interaction. Thus, the beneficial properties associated with Med diet in terms of glucose homeostasis may depend on an individual's genetic background.
Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from ...metabolic syndrome (MetS) affects this response is not established.
Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors.
In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined.
Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05).
Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features. This study was registered at clinicaltrials.gov as NCT00429195.
Scope
Branched Chain Amino Acids (BCAA) plasma levels may be differentially associated with type 2 diabetes mellitus (T2DM) remission through the consumption of the Mediterranean diet (Med) and a ...low‐fat (LF) diet.
Methods
One hundred eighty‐three newly diagnosed T2DM patients within the CORDIOPREV study are randomized to consume the Med or a LF diet. BCAA plasma levels (isoleucine, leucine, and valine) are measured at fasting and after 120 min of an oral glucose tolerance test (OGTT) at the baseline of the study and after 5 years of the dietary intervention.
Results
Isoleucine, leucine, and valine plasma levels after 120 min of an OGTT in the Med diet (N = 80) are associated by COX analysis with T2DM remission: HR per SD (95% CI): 0.53 (0.37–0.77), 0.75 (0.52–1.08), and 0.61 (0.45–0.82), respectively; no association is found in patients who consumed a LF diet (N = 103). BCAA plasma levels combined in a score show a HR of 3.33 (1.55–7.19) of T2DM remission for patients with a high score values in the Med diet, while in those with a LF diet, no association is found.
Conclusion
The study suggests that BCAA measurements potentially be used as a tool to select the most suitable diet to induce T2DM remission by nutritional strategies.
Type 2 diabetes mellitus remission may be induced by the consumption of healthy diets without a relevant weigh loss. The determination of BCAA in plasma may potentially be used as a tool to select the most suitable diet to induce T2DM remission by nutritional strategies. Low BCAA plasma levels are associated with T2DM remission when a Mediterranean diet is consumed; however, this is not observed for the case of low‐fat diet consumption.
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